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  • CLASSES

    Multi-Acting Receptor-Targeted Antipsychotics (MARTA)

    BOXED WARNING

    Abrupt discontinuation, children, suicidal ideation

    Quetiapine has not been FDA approved for use in children less than 10 years of age. In addition, a causal role has been demonstrated with antidepressant use and emergence of suicidal ideation in pediatrics and young adults; quetiapine is not approved for the treatment of depression in pediatric patients. There is no known indication for use of quetiapine in infants. The increased risk for suicidal ideation was identified in a pooled analysis of 24 placebo-controlled trials (n = 4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in the antidepressant groups. The clinical need for an antidepressant in children or young adults for any use must be weighed against the risk of increased suicidality; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose change; such observation would generally include at least weekly face-to-face contact with patients during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks; additional contact by telephone may be appropriate between visits. The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary psychiatric disorder. It is advisable to closely observe all patients for clinical worsening and suicidality, especially during the initial few months of antidepressant therapy, or at times of dose changes. Caregivers and/or patients should immediately notify the prescriber of agitation, irritability, unusual changes in behavior, or suicidality. A decision should be made to change or discontinue treatment in patients who exhibit changes in symptoms, worsening of depression or suicidality. If discontinuing, the medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. Prescriptions for quetiapine should be written for the smallest quantity of tablets possible to reduce the risk of overdose.

    Dementia, geriatric, stroke

    Clinical trials with quetiapine did not indicate a difference in tolerability in the geriatric patient vs. younger adult patients. Elderly patients may be more sensitive to the sedative, anticholinergic, and orthostatic effects of quetiapine; consider a slower rate of dose titration and lower target dose in the older adult. Atypical antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients. All atypical antipsychotic labels include a boxed warning regarding increased morbidity and mortality (1.6 to 1.7 times vs. placebo) reported in geriatric patients with dementia receiving atypical antipsychotics. Deaths typically occurred due to heart failure, sudden death, or infections (primarily pneumonia). An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. According to the Beers Criteria, antipsychotics are considered potentially inappropriate medications (PIMs) in elderly patients, and use should be avoided except for treating schizophrenia or bipolar disorder, and for short-term use as antiemetics during chemotherapy. Avoid use of quetiapine in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: delirium (possible new-onset or worsening delirium) and dementia (adverse CNS effects). There is an increased risk of stroke and a greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics. The Beers expert panel recommends avoiding antipsychotics to treat delirium- or dementia-related behavioral problems unless non-pharmacological options have failed or are not possible and the patient is a substantial threat to self or others. Avoid antipsychotics in elderly patients with a history of falls or fractures unless safer alternatives are not available since antipsychotics can cause ataxia, impaired psychomotor function, syncope, and new falls. If use is necessary, consider reducing the use of other CNS-active medications and implement other strategies to reduce fall risk. Because antipsychotics can cause or exacerbate hyponatremia and SIADH, particularly in the elderly, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. While it is recommended that most dopamine-receptor antagonists be avoided in patients with Parkinson's disease due to the potential to worsen parkinsonian symptoms, quetiapine appears less likely to precipitate a worsening of symptoms based on limited data vs. other antipsychotics and has been excluded from the recommendation. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). An antipsychotic should generally be used only for the conditions listed in the guidelines (e.g., schizophrenia, mood disorder, Tourette's disorder) and meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. The LTCF must identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic, as there is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. To initiate antipsychotic therapy, the patient must either be a danger to self or others or have symptoms due to mania or psychosis, and the plan of care should document attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less and evaluate/document within 7 days the contributors/causes to the symptoms. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. Treatment of non-acute, chronic, or prolonged BPSD must meet all of the OBRA criteria for BPSD treatment and ensure that the behavioral symptoms are not due to a treatable medical condition or correctable environmental or psychological stressors alone and the facility must provide documented evidence of persistence. The LTCF must evaluate the appropriateness of antipsychotic treatment during or within 2 weeks of admission for a newly admitted resident. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. In all cases, the lowest possible dose and the shortest duration should be prescribed and the facility should monitor for ongoing effectiveness and potential adverse effects. Antipsychotics are subject to periodic review for effectiveness, medical necessity/rationale for use, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    DEA CLASS

    Rx

    DESCRIPTION

    Atypical antipsychotic; structurally similar to clozapine; low risk of EPS and hyperprolactinemia
    Used in adults for the treatment of schizophrenia, mania associated with bipolar I disorder, bipolar depression, maintenance of bipolar I disorder, and as an adjunct to antidepressants for treatment-resistant major depressive disorder
    Also used for schizophrenia in adolescents and for mania associated with bipolar I disorder in pediatric patients 10 years and older
    As with all antipsychotics, boxed warning regarding increased mortality risk in elderly patients with dementia-related psychosis

    COMMON BRAND NAMES

    Seroquel, Seroquel XR

    HOW SUPPLIED

    Quetiapine/Quetiapine Fumarate/Seroquel Oral Tab: 25mg, 50mg, 100mg, 200mg, 300mg, 400mg
    Quetiapine/Quetiapine Fumarate/Seroquel XR Oral Tab ER: 50mg, 150mg, 200mg, 300mg, 400mg

    DOSAGE & INDICATIONS

    For the treatment of major depression.
    For the adjunctive treatment of major depression in patients who have had an inadequate response to antidepressants alone.
    Oral dosage (extended-release tablets)
    Adults

    50 mg PO once daily in the evening on Day 1 and Day 2. On Day 3, increase to 150 mg PO once daily in the evening. Effectiveness has been demonstrated at a range of 150 mg/day to 300 mg/day PO. Doses above 300 mg/day have not been studied. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. During clinical trials, a dose-dependent increase in adverse reactions was observed in the recommended dose range. Because of the frequency and severity of adverse effects with antipsychotics, it is advisable to reserve the use of quetiapine for patients refractory to traditional therapies for depression and whose severity of illness outweighs the long-term risks of treatment with an antipsychotic. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Geriatric adults

    50 mg PO once daily in the evening initially on Day 1 and Day 2. The dose may be increased in increments of 50 mg/day depending on individual response and tolerability within the adult dose range. Effectiveness has been demonstrated at a range of 150 mg/day to 300 mg/day PO. Doses above 300 mg/day have not been studied. Consider a slow rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Because of the frequency and severity of adverse effects with antipsychotics, it is advisable to reserve the use of quetiapine for patients refractory to traditional therapies for depression and whose severity of illness outweighs the long-term risks of treatment with an antipsychotic. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    For the treatment of major depressive disorder as monotherapy†.
    Oral dosage (extended-release formulation e.g., Seroquel XR)
    Adults

    50 mg/day PO initially, and titrate according to response and tolerability. Consider a slow rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension, such as the elderly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In large randomized clinical trials, quetiapine XR 50 mg/day PO up to 300 mg/day PO has been effective as monotherapy treatment and improvement may occur as early as Day 4 of treatment. Doses above 300 mg/day have not been studied. In one large comparison trial (n = 612) for patients with major depressive disorder (MDD), quetiapine XR 150 mg/day PO, quetiapine XR 300 mg/day PO, and duloxetine 60 mg/day PO showed significant improvement in the primary outcome, change in Montgomery-Asberg Depression Rating Scale (MADRS), compared to placebo; however, only the quetiapine XR 300 mg/day group and the duloxetine group were superior to placebo in MADRS remission rates (absolute score 8 or less). In a fixed-dose comparison of quetiapine XR 50 mg/day PO, 150 mg/day PO, 300 mg/day PO, and placebo in patients with MDD, all three active treatments significantly improved MADRS scores compared to placebo beginning on day 4 and throughout the study (6 weeks); however, only the 50 mg/day and 300 mg/day groups separated from placebo in remission rates. Overall, the 150 mg/day dose was associated with more positive secondary efficacy results than 50 mg/day and 300 mg/day versus placebo. The most common side effects were dry mouth, sedation, somnolence, headache, and dizziness. Further study is needed to determine the long-term risks and benefits of quetiapine in the monotherapy treatment of major depression. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    For the treatment of bipolar disorder, including mania and bipolar depression.
    For the acute treatment of mania and for maintenance therapy following stabilization.
    Oral dosage (immediate-release tablets)
    Adults

    Initially, 50 mg PO twice daily on Day 1 for adults not at risk for hypotension. Increase in increments of up to 100 mg/day in two divided doses as tolerated to 400 mg/day on Day 4. If needed, may further titrate up to 800 mg/day by Day 6 in increments of no greater than 200 mg/day. The recommended dosage range for acute mania is 400 mg/day to 800 mg/day as monotherapy or as an adjunct to lithium or divalproex. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Maximum: 800 mg/day PO, in two divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Clinical trials excluded patients with rapid cycling or mixed features. Periodically re-assess to determine the need for ongoing treatment. Efficacy of quetiapine as monotherapy for maintenance treatment of bipolar disorder has not been formally evaluated; therefore, when instituting maintenance therapy, use as an adjunct to lithium or divalproex. During clinical trials, patients were generally continued on the same dose on which they were stabilized during the acute phase of treatment. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Geriatric Adults

    Initially, 25 mg PO twice daily. Increase the dose in increments of 50 mg/day depending upon individual response and tolerability. The dosage range for acute mania in younger adults is 400 mg/day to 800 mg/day as monotherapy or as an adjunct to lithium or divalproex. Maximum: 800 mg/day PO, in two divided doses. Consider a slow rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Clinical trials excluded patients with rapid cycling or mixed features. Periodically re-assess to determine the need for ongoing treatment. Efficacy of quetiapine as monotherapy for maintenance treatment of bipolar disorder has not been formally evaluated; therefore, when instituting maintenance therapy, use as an adjunct to lithium or divalproex. During clinical trials, patients were generally continued on the same dose on which they were stabilized during the acute phase of treatment. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Children and Adolescents 10 years and older

    25 mg PO twice daily on Day 1, 50 mg PO twice daily on Day 2, 100 mg PO twice daily on Day 3, 150 mg PO twice daily on Day 4, and 200 mg PO twice daily beginning Day 5. Range: 400 mg/day to 600 mg/day based upon response and tolerability. If needed, administer in 3 divided doses per day to help with medication tolerance. Adjust dose in increments 100 mg/day or less. Maximum: 600 mg/day PO. If maintenance therapy is needed, use lowest effective dose and periodically re-evaluate need for continued treatment. Although efficacy was established at the 400 mg/day and 600 mg/day doses during clinical trials, there appears to be no additional benefit over the 400 mg/day dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Efficacy in bipolar mania was established in a single, 3-week, monotherapy trial. The efficacy of maintenance treatment of bipolar I disorder in adolescents and children has not been formally evaluated. If maintenance treatment is deemed necessary, the lowest effective dose for maintaining an adequate response is recommended. Periodic re-evaluation is suggested to assess the need for continued treatment. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Oral dosage (extended-release tablets)
    Adults

    300 mg PO once daily in the evening on Day 1 followed by 600 mg PO once daily in the evening on Day 2. Beginning on Day 3, the daily dosage may be adjusted based upon response and tolerability. The recommended dosage range for manic episodes with or without mixed features is 400 mg/day to 800 mg/day as monotherapy or as an adjunct to lithium or divalproex. Maximum: 800 mg/day PO. Consider a slower rate of dose titration and a lower target dose for debilitated patients and patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Periodically re-assess the need for ongoing treatment. Efficacy as monotherapy maintenance treatment has not been formally evaluated; therefore the recommended maintenance dose range is 400 mg/day to 800 mg/day as an adjunct to lithium or divalproex. During clinical trials, patients were generally continued on the same dose on which they were stabilized during the acute phase of treatment. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Geriatric Adults

    Initially, 50 mg/day PO in the evening. The dosage should be increased in increments of 50 mg/day depending upon individual response and tolerability. Dose range for manic episodes with or without mixed features in younger adults: 400 mg/day to 800 mg/day PO as monotherapy or as an adjunct to lithium or divalproex. Maximum: 800 mg/day PO. Consider slower titration and a lower target dose for debilitated patients and those at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Efficacy as monotherapy maintenance treatment has not been formally evaluated; therefore the recommended maintenance dose range is 400 mg/day to 800 mg/day as an adjunct to lithium or divalproex. Generally, continue on the same dose on which stabilized during the acute phase of treatment. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Children and Adolescents 10 years and older

    50 mg PO once in the evening on Day 1, 100 mg once in the evening on Day 2, 200 mg once daily in the evening on Day 3, 300 mg once daily in the evening on Day 4, and 400 mg once daily in the evening on Day 5. Thereafter, adjust dose within the recommended dose range of 400 mg/day to 600 mg/day PO based upon response and tolerability. Maximum: 600 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Efficacy in bipolar mania was extrapolated from a 3-week, monotherapy trial of immediate-release quetiapine. The efficacy of maintenance treatment of bipolar I disorder in adolescents and children has not been formally evaluated. If maintenance therapy is necessary, use the lowest dose that maintains adequate response. Periodically re-assess the need for continued treatment. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    For the treatment of bipolar depression during depressive episodes of bipolar I or bipolar II disorder.
    Oral dosage (immediate-release or extended-release tablets)
    Adults

    Dosing is once daily at bedtime, regardless of immediate-release or extended-release oral dosage forms. Initially, 50 mg PO at bedtime on Day 1, then increase bedtime dose to 100 mg on Day 2, 200 mg on Day 3. Beginning on Day 4, increase to the recommended dose of 300 mg PO once daily at bedtime. Maximum for bipolar depression: 300 mg/day PO. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension, such as the elderly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    For the treatment of rapid-cycling† bipolar disorder.
    Oral dosage (immediate-release tablets)
    Adults

    In clinical trials for bipolar disorder for FDA-approval, patients with rapid-cycling or mixed episodes were excluded. However, quetiapine has been studied in rapid-cycling adult patients. In an open-label study, 50 mg PO once daily was added to an existing regimen of lithium, valproate, and/or carbamazepine; quetiapine was then titrated to response. Rapid-cycling patients with mania (n = 5), mixed episodes (n = 3), depression (n = 3), hypomania (n = 2), and euthymia (n = 1) were included. Initial effective doses of quetiapine were significantly reduced by the end of the study (mean dose 443 mg/day vs. 268 mg/day) and they also differed according to the initial episode being treated (mean dose 720 mg/day for mania vs. 183 mg/day for depression). A significant reduction in manic symptoms occurred; however, improvement in depressive symptoms was not significant. According to the study, 6 patients achieved complete remission. A separate open-label, long-term study evaluated 41 rapid-cycling patients receiving quetiapine as monotherapy or add-on therapy for up to 1 year. An initial dose of 50 mg/day, followed by titration to a target dose of 150 mg/day to 200 mg/day was used. The final mean maximal dosing was 196 mg/day (range: 25 mg/day to 900 mg/day). For the total sample, 41% and 29% of those with manic or depressive symptoms, respectively, responded to treatment with quetiapine. In the monotherapy subgroup, 50% of those with mania and 0% of those depressive symptoms were responders. Overall, 37% of subjects showed a response to quetiapine. Early termination occurred in 68.3% of subjects due to lack of efficacy (26.8%), non-adherence (12.2%), adverse effects (9.8%), affective episodes (9.8%), administrative (4.9%), drug abuse (2.4%), and intolerance (2.4%). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of schizophrenia.
    Oral dosage (immediate-release tablets)
    Adults

    25 mg PO twice daily on Day 1. Increase by 25 mg to 50 mg, on Day 2 and Day 3 to a target range of 300 mg/day to 400 mg/day PO, in divided doses two or three times per day, by Day 4. Further dosage adjustments can be made in increments/decrements of 25 mg to 50 mg twice a day, at intervals of at least 2 days, within the initial recommended dose range of 150 mg/day to 750 mg/day. The recommended maintenance dose range is 400 mg/day to 800 mg/day. Maximum: 800 mg/day PO. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Efficacy in adults was established in three short-term (6-week) controlled trials in inpatients. In short-term clinical trials evaluating 5 doses (i.e., daily doses of 75 mg, 150 mg, 300 mg, 600 mg, or 750 mg), the maximum benefit as measured by the BPRS total score, the BPRS psychosis cluster, and the CGI severity score, occurred at a dose of 300 mg/day. The 75 mg dose was not superior to placebo. In other short-term clinical trial evaluation, high dose treatment (450 mg/day to 750 mg/day) was superior to low dose treatment (250 mg/day or less). Long-term use in schizophrenia has not been systematically evaluated. Periodically re-assess to determine the need for continued therapy. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Geriatric adults

    Initially, 25 mg PO twice daily and increase based upon individual response and tolerability. Compared to the adult dosing schedule, a slower rate of titration and a lower target dose should be considered for geriatric or debilitated patients, and patients predisposed to hypotension. The younger adult target range is 300 mg/day to 400 mg/day PO, in divided doses two or three times per day. Adjust in increments/decrements of 25 mg to 50 mg twice a day, at intervals of at least 2 days, within range of 150 mg/day to 750 mg/day. Usual younger adult maintenance dose range: 400 mg/day to 800 mg/day. Maximum: 800 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Adolescents

    25 mg PO twice daily on Day 1, then 50 mg PO twice daily on Day 2, 100 mg PO twice daily on Day 3, 150 mg PO twice daily on Day 4, and 200 mg PO twice daily beginning on Day 5. Thereafter, dosage adjustments may be made within the dose range of 400 mg/day to 800 mg/day, given in two or three divided doses based upon response and tolerability. Make dose adjustments in increments of 100 mg/day or less. Based on clinical trials, there appears to be no additional benefit at doses greater than 400 mg/day. Individualize. Long-term use in schizophrenia has not been systematically evaluated. Use lowest effective dose. Periodically re-assess the need for continued treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Oral dosage (extended-release tablets i.e., Seroquel XR)
    Adults

    Initially, 300 mg PO once daily, preferably in the evening. Titrate to a range of 400 mg to 800 mg PO once daily, based on response and tolerability. The dose may be increased in increments up to 300 mg/day and at intervals of at least 1 day each. Maximum: 800 mg/day PO. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Patients currently receiving the immediate-release formulation may be switched to the extended-release formulation at the equivalent total daily dose taken once daily. Individualize dosage. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    Geriatric adults

    An initial dose of 50 mg/day PO is recommended for geriatric patients. The dosage may be titrated in increments of 50 mg/day depending upon individual response and tolerability. Younger adult dose range: 400 mg to 800 mg PO once daily, based on response and tolerability. Maximum: 800 mg/day PO. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Patients currently receiving the immediate-release formulation may be switched to the extended-release formulation at the equivalent total daily dose taken once daily. Individualize dosage. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule. 

    Adolescents

    Initially, 50 mg PO on Day 1. Thereafter, use the following titration schedule: 100 mg/day on Day 2, 200 mg/day on Day 3, 300 mg/day on Day 4, and 400 mg PO once daily beginning on Day 5. Adjust based upon response and tolerability within the recommended dose range of 400 mg/day to 800 mg/day. Maximum: 800 mg/day PO. Periodically re-assess the need for continued treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.

    For the adjunct treatment of refractory obsessive-compulsive disorder (OCD)†.
    Oral dosage (immediate-release tablets)
    Adults

    Dosage not established. Quetiapine use cannot be routinely recommended; although, quetiapine has been studied as an adjunct to either an SSRI or clomipramine, which have been previously titrated to optimal doses for OCD. Randomized controlled trials have shown mixed results for the adjunct treatment of OCD. Several of these trials have not proven a benefit for add-on therapy with quetiapine vs. placebo. Initial doses: 25 mg or 50 mg PO once daily; dose may be administered at bedtime. The dose is typically titrated at weekly intervals, as tolerated and clinically indicated. In a well-controlled clinical trial, the target dose of quetiapine after titration was 200 mg/day PO. Trials have allowed doses up to 300 mg/day to 600 mg/day PO, in divided doses. Somnolence is the major side effect. Use with caution in patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Larger controlled clinical trials are needed to validate any long-term efficacy, as well as effectiveness when co-morbid disease states exist.

    For the treatment of neurocognitive symptoms (e.g., impulsivity, executive functioning) associated with borderline personality disorder†.
    Oral dosage (extended-release tablets)
    Adults

    Further study is needed to establish the effective dose range. Benefit-to-risk should be thoroughly evaluated prior to initiating treatment. Data suggest that 150 mg PO once daily dosing provides the best benefit-to-risk ratio, after titration. In one placebo-controlled, randomized study, use of 150 mg/day (low-dose) resulted in statistically significant improvement on the primary endpoint (Zanarini scale total score), but 300 mg/day (moderate-dose) did not separate from placebo. The initial dose: 50 mg PO once daily for 1 week, followed by titration to 150 mg PO once daily, with subsequent titration of the higher dose group to 300 mg/day PO after 4 weeks. Among those completing the study, 82% in the low-dose quetiapine group were responders vs. 74% in the moderate-dose group and vs. 48% in the placebo group (responder defined as a reduction of 50% or more on the Zanarini scale total score). Baseline symptom severity was greatest in the 300 mg/day group and least for the placebo group (p = 0.029), which may have confounded the results. The time to response was significantly shorter for both the low-dose and moderate-dose quetiapine groups vs. placebo. There were significant improvements in both quetiapine groups on some secondary measures, such as self-rated Zanarini subscales for affective disturbance, cognitive disturbance, and disturbed relationships and the clinician-rated aggression scale score. Unlike other studies, impulsivity was not significantly improved. Common side effects included sedation, change in appetite, and dry mouth. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Periodically re-assess the need for continued therapy.

    Oral dosage (immediate-release tablets)
    Adults

    Evaluate benefit-to-risk prior to treatment. Initially, use low doses of 25 mg to 50 mg PO twice daily to minimize side effects (e.g., orthostatic hypotension), followed by titration as clinically indicated and tolerated. Studies indicate an average effective dose range of 250 mg/day to 550 mg/day PO, given in divided doses (range: 100 mg/day to 800 mg/day PO). Maximum: 800 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Quetiapine may improve impulsivity, hostility, and affective symptoms, and results of one study suggests improvement of executive functioning. Common side effects include somnolence, dizziness, increased appetite, and dry mouth. Somnolence is the primary side effect associated with discontinuation. Periodically re-assess the need for continued therapy. Most studies are limited by open-label design, lack of controls, high dropout rates, and small sample sizes.

    For the treatment of severe behavioral or psychological symptoms of dementia† (BPSD)†.
    Oral dosage (immediate-release tablets)
    Geriatric Adults

    Initially, 25 mg PO once or twice daily. Dosage adjustments of 25 mg to 50 mg twice per day, if indicated, should occur at intervals of not less than 2 to 7 days. The effective dose range has not been established, but a maximum of 150 mg/day has been suggested. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The U.S. Agency for Healthcare Research and Quality (AHRQ) evidence reviews indicate that while studies of quetiapine are considered too clinically dissimilar to pool, results for the individual studies show, with one exception, trends favoring quetiapine that do not reach conventional levels of statistical significance for 3 dementia categories reviewed: dementia-overall behavioral symptoms, dementia-psychosis symptoms, and dementia-agitation symptoms. Antipsychotics are not FDA-approved for the treatment of behavioral problems associated with dementia and the labeling of all antipsychotics contains a boxed warning noting an increased risk of death in geriatric patients being treated for behavioral problems associated with dementia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antipsychotics in long-term care facility (LTCF) residents with dementia-related behavioral symptoms. OBRA Max: 150 mg/day PO in residents meeting the OBRA criteria for treatment, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. In addition, the facility must attempt a gradual dose reduction (GDR) in 2 separate quarters, at least 1 month apart, within the first year of admission to the facility or after the facility has initiated an antipsychotic, unless clinically contraindicated. After the first year, a GDR must be attempted annually unless clinically contraindicated. The GDR may be considered clinically contraindicated if the target symptoms returned or worsened after the most recent GDR attempt within the facility and the physician has documented justification for why attempting additional dose reductions at that time would likely impair the resident's function or increase distressed behavior.

    For the treatment of neuropsychiatric symptoms associated with dementia with Lewy bodies† that are unresponsive to other medications and non-medication treatments.
    Oral dosage (immediate-release tablet)
    Adults, including Geriatric Adults

    The labeling of all antipsychotics contains a boxed warning noting an increased risk of death in elderly patients with dementia-related psychosis being treated with antipsychotics. Initially, 25 mg PO once daily, with titration by 25 mg once or twice daily at intervals not less than 2 to 7 days, if clinically indicated and tolerated. Low-dose quetiapine 25 mg/day to 75 mg/day PO was effective in treating psychosis and agitation in about 50% of patients in 1 case series. Conversely, a small study (n = 40) evaluated mixed populations including patients with dementia with Lewy bodies, Parkinson disease with dementia, or Alzheimer’s disease with parkinsonian features; there was no significant difference between quetiapine and placebo for the primary outcome, change in total Brief Psychiatric Rating Scale (BPRS) score from baseline to 10 weeks; quetiapine was titrated from 25 mg PO once daily at bedtime up to a maximum dose of 150 mg PO twice daily, given morning and evening; the mean tolerated dose was 120 mg/day PO in divided doses. The U.S. Agency for Healthcare Research and Quality (AHRQ) evidence reviews indicate that studies of quetiapine are too clinically dissimilar to pool, and results show, with one exception, trends favoring treatment with quetiapine that do not reach conventional levels of statistical significance for 3 dementia categories reviewed: dementia-overall behavioral symptoms, dementia-psychosis symptoms, and dementia-agitation symptoms. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antipsychotics in long-term care facility (LTCF) residents with dementia-related behavioral symptoms. Max: 150 mg/day PO in residents meeting criteria for treatment, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Not definitive, 800 mg/day PO suggested. Debilitated and/or patients at risk for hypotension may require lower dosages.

    Geriatric

    Not definitive, 200—800 mg/day PO suggested. Debilitated and/or patients at risk for hypotension may require lower dosages.

    Adolescents

    800 mg/day PO.

    Children

    > = 10 years: 600 mg/day PO.
    < 10 years: Safety and effectiveness have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Patients with hepatic impairment have a 30% lower mean clearance of quetiapine than normal subjects; therefore, initial dosage adjustment is necessary.
    Immediate-release formulation: Initiate with 25 mg/day PO. The dose should be increased daily in increments of 25 to 50 mg/day to an effective dose and given in divided doses twice daily, depending on the clinical response and tolerability of the patient. 
    Extended-release formulation: Initially, give 50 mg PO once daily, preferably in the evening. The dose can be increased daily in increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient.

    Renal Impairment

    CrCl 10 mL/minute and above: No dosage adjustment is needed. Although patients with severe renal impairment (10 to 30 mL/minute) have a 25% lower mean clearance than normal subjects (CrCl more than 80 mL/minute), plasma quetiapine concentrations are still within the range of concentrations seen in normal subjects receiving the same dose.
    CrCl less than 10 mL/minute: There are no dosing guidelines available.
     
    Intermittent hemodialysis:
    There are no dosing guidelines available for patients with CrCl less than 10 mL/minute or those receiving dialysis.

    ADMINISTRATION

    A Med Guide is available that provides information about the risks of antidepressant use in pediatric patients.
    When restarting patients on quetiapine who have been off of the drug for more than one week, the initial titration schedule should be followed.

    Oral Administration

    Immediate-release tablets: May be administered without regard to meals.
    Extended-release tablets: May be administered without food or with a light meal (approximately 300 calories). Swallow whole. Do not split, chew, or crush tablets.

    STORAGE

    Seroquel:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Seroquel XR:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Quetiapine use is contraindicated in anyone with a known hypersensitivity to quetiapine or to any excipients in the quetiapine formulation. The drug carries a risk of serious hypersensitivity or anaphylaxis. Anaphylactic reactions, serious skin rashes, and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported in patients treated with quetiapine.
     
    Some reports suggest that a false positive urine drug screen may occur for methadone and tricyclic antidepressants in patients who have received quetiapine. Caution should be exercised when interpreting positive urine drug screens for these medications, and confirmation by alternate analytical techniques should be considered.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, cerebrovascular disease, coronary artery disease, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, hypotension, hypovolemia, long QT syndrome, malnutrition, myocardial infarction, orthostatic hypotension, QT prolongation, thyroid disease

    During post-marketing use of quetiapine, there have been cases of QT prolongation in patients with risk factors for developing QT prolongation such as overdose, concomitant illness, and in patients taking medications known to cause electrolyte imbalance or prolong the QT interval. Some drugs that prolong the QT interval have been associated with the development of torsade de pointes (TdP), a life-threatening arrhythmia. Existent QT prolongation increases the risk of TdP. Although TdP occurred in 1 patient receiving low-dose quetiapine, the exact contribution of the drug cannot be determined due to the presence of multiple medical conditions and risk factors. Use quetiapine with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, elderly patients, patients with diabetes, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation. Quetiapine can cause orthostatic hypotension associated with dizziness, tachycardia, and in rare cases, syncope. Orthostatic hypotension is most likely to occur during the initial dosage titration period and is thought to be caused by alpha-1 adrenergic blockade, resulting in peripheral vasodilation. Quetiapine should be used with caution in patients with pre-existing hypotension or cerebrovascular disease. Orthostatic hypotension could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate orthostasis. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Conditions that may predispose patients to hypotension, such as hypovolemia or a dehydrated state, should be corrected, if possible, before starting quetiapine therapy. Lower doses may be required in patients at increased risk for hypotension. Clinical trial data indicate that hypertension has occurred during quetiapine therapy in both adult and pediatric patients. Monitor blood pressure in pediatric patients at the beginning of and periodically during treatment, and in adults as clinically indicated.

    Agranulocytosis, hematological disease, leukopenia, neutropenia

    Quetiapine should be used with caution in patients with hematological disease. Hematologic effects including leukopenia, neutropenia, and agranulocytosis have been associated with antipsychotic use. Agranulocytosis (severe neutropenia) has been reported with quetiapine, including fatal cases and cases in patients without pre-existing risk factors. Neutropenia should be considered in patients presenting with infection, particularly in the absence of obvious predisposing factor(s), or in patients with unexplainable fever, and such patients should be managed as clinically indicated. A history of drug-induced leukopenia or neutropenia or pre-existing low white blood cell (WBC) count may increase the likelihood of developing hematologic effects during treatment with an antipsychotic. Patients with a history of clinically significant low WBC count or drug-induced leukopenia/neutropenia should have frequent complete blood count (CBC) assessments during the first few months of treatment. Discontinuation of quetiapine should be considered if a clinically significant decline in WBC occurs in the absence of an identifiable cause. Patients with clinically significant neutropenia should be closely monitored for fever and infection, and appropriate medical intervention should be instituted if necessary. Quetiapine should be discontinued in patients with severe neutropenia (ANC less than 1,000/mm3); ongoing medical care is recommended until the symptoms resolve.

    Cataracts

    Quetiapine was associated with the development of cataracts in animal studies. Lens changes have also been observed with long-term therapy in humans, however, a causal relationship has not been established. Nevertheless, examination of the lens by methods adequate to detect cataract formation is recommended upon initiation of quetiapine or shortly thereafter, and at six month intervals during chronic treatment.

    Hypothyroidism

    Quetiapine has been associated with dose-dependent decreases in total and free thyroxine (T4), or increase in thyroid stimulating hormone (TSH). Maximal effects are usually apparent in the first 2—4 weeks of treatment. In clinical trials with extended-release quetiapine, decreases in T4 occurred in 0.5% of those on active drug versus none on placebo; 2.7% of those on extended-release quetiapine experienced increased TSH versus 1.2% on placebo. No cases of hypothyroidism were reported in these studies. In clinical trials with immediate-release quetiapine, decreases in T4 of about 20% occurred at the higher end of the dose range. Although most of these changes were not clinically significant, a few cases of clinically relevant hypothyroidism were reported. Patients should be monitored for signs and/or symptoms of hypothyroidism during treatment with quetiapine. Reversal of effects generally occurs after discontinuation of the drug.

    Tardive dyskinesia

    Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotics. Periodic evaluation for movement disorders is recommended (e.g., AIMS). Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the initiation of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotics differ in their potential to cause tardive dyskinesia is unknown. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotics administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief periods at low doses or may even arise after drug discontinuation. The syndrome may remit, partially or completely, if the antipsychotic is withdrawn. Antipsychotics may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, quetiapine should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that is known to respond to antipsychotics, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic therapy, the smallest dose and the shortest duration producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear, quetiapine discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

    Dysphagia

    Patients with dysphagia or who are at risk for aspiration pneumonia should be closely monitored while receiving quetiapine. Antipsychotic drug use has been associated with esophageal dysmotility and aspiration of gastric contents, which may increase the incidence of aspiration pneumonia in certain patient populations, such as patients with advanced Alzheimer's disease.

    Neurological disease, Parkinson's disease

    Antipsychotics can cause motor and sensory instability, which may lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with diseases (e.g., neurological disease), conditions, or concurrent medication use that could exacerbate motor and sensory instability. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Quetiapine should be used with caution in patients with Parkinson's disease because of possible development of extrapyramidal symptoms.

    Brain tumor, seizure disorder

    In clinical trials with extended-release quetiapine, seizures were reported in 0.1% of those on active drug versus 0.9% on placebo. In clinical trials with immediate-release quetiapine, seizures occurred in 0.6% of patients on active drug versus 0.2% on placebo. Quetiapine should be used with caution in patients with a seizure disorder or with conditions that may lower the seizure threshold (e.g. brain tumor, cerebrovascular disease).

    Coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion

    Somnolence is a commonly reported adverse effect of quetiapine, and may result in impairment of cognitive and motor skills. The sedative effects of quetiapine may be most evident in the initial days of treatment; patients should be advised to use caution when driving or operating machinery, or performing other tasks that require mental alertness, until they know how quetiapine affects them. Somnolence could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate somnolence. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Given the primary CNS effects of quetiapine, caution should be used during coadministration with other CNS depressants and alcohol. Ethanol ingestion may further impair cognitive and motor skills and patients should be advised to avoid use of alcoholic beverages.

    Hepatic disease

    Quetiapine is extensively metabolized in the liver. During controlled clinical trials of immediate-release quetiapine in patients with schizophrenia, approximately 6% of those receiving quetiapine developed transaminase elevations greater than 3 times the upper limits of normal compared to 1% of those receiving placebo. The incidence of elevated hepatic enzymes in those receiving quetiapine for either bipolar mania or bipolar depression was similar between active drug and placebo groups (approximately 1—2%). Transaminase elevations greater than 3 times the upper limits of normal occurred in 1% and 2% of those receiving extended-release quetiapine and placebo, respectively. This drug should be used with caution in patients with hepatic disease because of the possibility of reduced drug clearance. A slower rate of dose titration and a lower target dose should be considered.

    Breast cancer

    Significant increases in serum prolactin concentrations ocurred during clinical trials with quetiapine across all incidications. Increased prolactin concentrations were observed in rat studies and were associated with an increase in mammary gland neoplasia. There is insufficient evidence linking chronic administration of antipsychotics with tumorigenesis in humans. However, because up to one-third of human breast cancer cases may be prolactin dependent (based on in vitro studies), quetiapine should be used with caution in women with breast cancer.

    Diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, obesity

    In epidemiological studies and case reports, atypical antipsychotics, including quetiapine, have been associated with metabolic changes, including elevations in blood glucose and lipids, decreased insulin sensitivity, precipitation or unmasking of diabetes mellitus in susceptible patients, ketoacidosis, hyperosmolar coma, and death. Patients with pre-existing diabetes mellitus should be monitored regularly while receiving quetiapine. Diabetic patients should be instructed to monitor their blood glucose levels and watch for signs of excessive urination, thirst, and hunger while taking atypical antipsychotics. Patients with risk factors for diabetes, such as obesity or a family history of diabetes should undergo fasting glucose testing at baseline and periodically throughout treatment. All patients receiving an atypical antipsychotic should be monitored for symptoms of hyperglycemia such as polydipsia, polyuria, polyphagia, and/or weakness. Patients developing signs or symptoms suggestive of diabetes while receiving an atypical antipsychotic should be tested for diabetes. In some cases, continued antidiabetic treatment has been necessary despite discontinuation of the antipsychotic agent. Study data indicate that elevations in cholesterol to at least 240 mg/dL and triglycerides to at least 200 mg/dL occur more frequently with immediate-release quetiapine (16% and 23%, respectively) compared to placebo (7% and 16%, respectively) in patients with schizophrenia. The use of similar cholesterol parameters in trials of patients with bipolar depression showed a 9% frequency of elevated cholesterol in those receiving quetiapine versus 6% in the placebo group, and elevated triglycerides in 14% of quetiapine patients versus 9% of those receiving placebo. Extended-release quetiapine has been associated with elevations in cholesterol and triglycerides (elevations of 4% and 15%, respectively) in contrast to decreases with placebo (decreases of 2% and 6%, respectively). It is advisable to monitor cholesterol and triglyceride concentrations periodically in patients receiving antipsychotics, particularly those with pre-existing hypercholesterolemia or hypertriglyceridemia.

    Neonates, pregnancy, pregnancy testing

    There are no adequate and well-controlled studies of quetiapine in pregnant women; therefore, quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In animal studies during the period of organogenesis, evidence of embryo/fetal toxicity was observed, including delays in skeletal ossification, minor soft tissue anomalies, and reduced body weight. In addition, maternal toxicity (decreases in body weight gain and/or death) was observed in these studies. Neonates exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity and have ranged from self-limited to those requiring intensive care unit support and prolonged hospitalization. Neonates exhibiting signs or symptoms of extrapyramidal effects or withdrawal should be carefully monitored. The knowledge about long-term neurobehavioral effects in offspring is limited for all antipsychotic agents and requires further investigation. According to the American Psychiatric Association treatment guidelines for schizophrenia, consider pregnancy testing in women of childbearing potential prior to initiation of an antipsychotic. The National Pregnancy Registry for Psychiatric Medications is dedicated to evaluating the safety of psychiatric medications that may be taken by women during pregnancy to treat a wide range of mood, anxiety, or psychiatric disorders. The primary goal of this Registry is to determine the frequency of major malformations, such as heart defects, cleft lip, or neural tube defects, in babies exposed to various psychiatric drugs during pregnancy. While the research concentrates on atypical antipsychotics and antidepressant use, pregnant women using other psychiatric medications are encouraged to register. For more information, contact the registry at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by phone 1-866-961-2388. It is not known if antipsychotics, through their effect on prolactin, would affect labor or obstetric delivery.

    Breast-feeding

    According to the manufacturer, quetiapine is excreted into human breast milk and a decision should be made to discontinue breast-feeding or the drug, taking into account the importance of the drug to the mother's health. Case reports have indicated that the level of quetiapine in breast milk ranges from undetectable to 170 mcg/L; the estimated infant dose ranged from 0.09% to 0.43% of the weight-adjusted maternal dose. Limited data of mother/infant pairs (n = 8) have indicated that the calculated infant daily doses range from less than 0.01 mg/kg for a maternal dose up to 100 mg/day to 0.1 mg/kg for a maternal dose of 400 mg/day. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing quetiapine regimen if ongoing treatment is deemed necessary during breast-feeding. However, olanzapine may be considered as an alternate atypical agent. Data related to the safety of antipsychotics during breast-feeding are limited and chronic administration of any antipsychotic during breast-feeding should be avoided if possible. Regardless of the antipsychotic used, the nursing infant should be closely monitored for excessive drowsiness, lethargy, and developmental delays. Combination treatment with antipsychotics may increase the risk of these adverse events. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Abrupt discontinuation, children, suicidal ideation

    Quetiapine has not been FDA approved for use in children less than 10 years of age. In addition, a causal role has been demonstrated with antidepressant use and emergence of suicidal ideation in pediatrics and young adults; quetiapine is not approved for the treatment of depression in pediatric patients. There is no known indication for use of quetiapine in infants. The increased risk for suicidal ideation was identified in a pooled analysis of 24 placebo-controlled trials (n = 4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in the antidepressant groups. The clinical need for an antidepressant in children or young adults for any use must be weighed against the risk of increased suicidality; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose change; such observation would generally include at least weekly face-to-face contact with patients during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks; additional contact by telephone may be appropriate between visits. The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary psychiatric disorder. It is advisable to closely observe all patients for clinical worsening and suicidality, especially during the initial few months of antidepressant therapy, or at times of dose changes. Caregivers and/or patients should immediately notify the prescriber of agitation, irritability, unusual changes in behavior, or suicidality. A decision should be made to change or discontinue treatment in patients who exhibit changes in symptoms, worsening of depression or suicidality. If discontinuing, the medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. Prescriptions for quetiapine should be written for the smallest quantity of tablets possible to reduce the risk of overdose.

    Dementia, geriatric, stroke

    Clinical trials with quetiapine did not indicate a difference in tolerability in the geriatric patient vs. younger adult patients. Elderly patients may be more sensitive to the sedative, anticholinergic, and orthostatic effects of quetiapine; consider a slower rate of dose titration and lower target dose in the older adult. Atypical antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients. All atypical antipsychotic labels include a boxed warning regarding increased morbidity and mortality (1.6 to 1.7 times vs. placebo) reported in geriatric patients with dementia receiving atypical antipsychotics. Deaths typically occurred due to heart failure, sudden death, or infections (primarily pneumonia). An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. According to the Beers Criteria, antipsychotics are considered potentially inappropriate medications (PIMs) in elderly patients, and use should be avoided except for treating schizophrenia or bipolar disorder, and for short-term use as antiemetics during chemotherapy. Avoid use of quetiapine in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: delirium (possible new-onset or worsening delirium) and dementia (adverse CNS effects). There is an increased risk of stroke and a greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics. The Beers expert panel recommends avoiding antipsychotics to treat delirium- or dementia-related behavioral problems unless non-pharmacological options have failed or are not possible and the patient is a substantial threat to self or others. Avoid antipsychotics in elderly patients with a history of falls or fractures unless safer alternatives are not available since antipsychotics can cause ataxia, impaired psychomotor function, syncope, and new falls. If use is necessary, consider reducing the use of other CNS-active medications and implement other strategies to reduce fall risk. Because antipsychotics can cause or exacerbate hyponatremia and SIADH, particularly in the elderly, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. While it is recommended that most dopamine-receptor antagonists be avoided in patients with Parkinson's disease due to the potential to worsen parkinsonian symptoms, quetiapine appears less likely to precipitate a worsening of symptoms based on limited data vs. other antipsychotics and has been excluded from the recommendation. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). An antipsychotic should generally be used only for the conditions listed in the guidelines (e.g., schizophrenia, mood disorder, Tourette's disorder) and meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. The LTCF must identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic, as there is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. To initiate antipsychotic therapy, the patient must either be a danger to self or others or have symptoms due to mania or psychosis, and the plan of care should document attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less and evaluate/document within 7 days the contributors/causes to the symptoms. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. Treatment of non-acute, chronic, or prolonged BPSD must meet all of the OBRA criteria for BPSD treatment and ensure that the behavioral symptoms are not due to a treatable medical condition or correctable environmental or psychological stressors alone and the facility must provide documented evidence of persistence. The LTCF must evaluate the appropriateness of antipsychotic treatment during or within 2 weeks of admission for a newly admitted resident. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. In all cases, the lowest possible dose and the shortest duration should be prescribed and the facility should monitor for ongoing effectiveness and potential adverse effects. Antipsychotics are subject to periodic review for effectiveness, medical necessity/rationale for use, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    Ambient temperature increase, dehydration, hyperthermia, hypothermia, strenuous exercise

    Antipsychotics have been reported to disrupt the body's ability to reduce core body temperature presumably through effects in the hypothalamus, and they predispose patients to hyperthermia. Patients receiving quetiapine should be advised of conditions that contribute to an elevation in core body temperature (e.g., strenuous exercise, ambient temperature increase, or dehydration). A less frequently described alteration in thermoregulatory processes reported with both conventional and atypical antipsychotics is hypothermia. Thermoregulation is multi-factorial; however, the dopaminergic system appears to have a primary role, and serotonin may also have modulatory activity (5-HT2a receptors). Most cases of hypothermia associated with antipsychotics have occurred in conjunction with other potential precipitating factors such as hypothyroidism, sepsis, organic brain injury, or environmental temperature. Hypothermia appears to occur more frequently during initiation of antipsychotic therapy or after dose increases.

    Anticholinergic medications, constipation, increased intraocular pressure, prostatic hypertrophy, urinary retention

    Quetiapine should be used cautiously in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or increased intraocular pressure. Norquetiapine, the active metabolite of quetiapine, is thought to be associated with the anticholinergic effects observed during clinical use of quetiapine, during concurrent use of quetiapine and anticholinergic medications, and following overdose of quetiapine. Intestinal obstruction has been reported with quetiapine, including fatal reports in patients who were also receiving multiple medications that decrease intestinal motility.

    Infertility, reproductive risk

    Quetiapine may pose a reproductive risk by increasing serum prolactin concentrations, which may lead to reversible infertility in females of reproductive potential.

    ADVERSE REACTIONS

    Severe

    suicidal ideation / Delayed / 0.1-1.3
    tardive dyskinesia / Delayed / 0.1-1.0
    GI bleeding / Delayed / 0.1-1.0
    stroke / Early / 0.1-1.0
    cyanosis / Early / 0.1-1.0
    bone fractures / Delayed / 0.1-1.0
    seizures / Delayed / 0.1-0.5
    GI obstruction / Delayed / 0-0.1
    pancreatitis / Delayed / 0-0.1
    hematemesis / Delayed / 0-0.1
    AV block / Early / 0-0.1
    atrial fibrillation / Early / 0-0.1
    heart failure / Delayed / 0-0.1
    exfoliative dermatitis / Delayed / 0-0.1
    water intoxication / Delayed / 0-0.1
    ocular hypertension / Delayed / 0-0.1
    hearing loss / Delayed / 0-0.1
    renal failure (unspecified) / Delayed / 0-0.1
    torsade de pointes / Rapid / Incidence not known
    neuroleptic malignant syndrome / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    bowel ischemia / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    apnea / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    myocarditis / Delayed / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    hypertensive crisis / Early / Incidence not known

    Moderate

    hypertension / Early / 1.0-41.0
    hypertriglyceridemia / Delayed / 8.0-22.0
    hypercholesterolemia / Delayed / 7.0-18.0
    withdrawal / Early / 12.1-12.1
    constipation / Delayed / 6.0-11.0
    orthostatic hypotension / Delayed / 2.0-10.0
    sinus tachycardia / Rapid / 1.0-8.0
    dystonic reaction / Delayed / 0-5.6
    pseudoparkinsonism / Delayed / 0-5.5
    akathisia / Delayed / 0-5.4
    dysarthria / Delayed / 1.0-5.0
    elevated hepatic enzymes / Delayed / 3.0-5.0
    palpitations / Early / 4.0-4.0
    blurred vision / Early / 1.0-4.0
    peripheral edema / Delayed / 4.0-4.0
    dyskinesia / Delayed / 0-3.8
    hyperprolactinemia / Delayed / 3.6-3.6
    hypotension / Rapid / 1.0-3.0
    depression / Delayed / 1.0-3.0
    amblyopia / Delayed / 2.0-3.0
    hyperglycemia / Delayed / 1.4-2.6
    confusion / Early / 0.1-2.0
    migraine / Early / 0.1-2.0
    ataxia / Delayed / 2.0-2.0
    hypothyroidism / Delayed / 0.1-2.0
    dysphagia / Delayed / 2.0-2.0
    QT prolongation / Rapid / 0.1-1.0
    amnesia / Delayed / 0.1-1.0
    psychosis / Early / 0.1-1.0
    hallucinations / Early / 0.1-1.0
    myoclonia / Delayed / 0.1-1.0
    teeth grinding (bruxism) / Delayed / 0.1-1.0
    fecal incontinence / Early / 0.1-1.0
    hemorrhoids / Delayed / 0.1-1.0
    stomatitis / Delayed / 0.1-1.0
    oral ulceration / Delayed / 0.1-1.0
    gastritis / Delayed / 0.1-1.0
    bundle-branch block / Early / 0.1-1.0
    atopic dermatitis / Delayed / 0.1-1.0
    skin ulcer / Delayed / 0.1-1.0
    contact dermatitis / Delayed / 0.1-1.0
    hyperthyroidism / Delayed / 0.1-1.0
    diabetes mellitus / Delayed / 0.1-1.0
    hypoglycemia / Early / 0.1-1.0
    anemia / Delayed / 0.1-1.0
    eosinophilia / Delayed / 0.1-1.0
    mania / Early / 0.1-1.0
    conjunctivitis / Delayed / 0.1-1.0
    blepharitis / Early / 0.1-1.0
    myasthenia / Delayed / 0.1-1.0
    bone pain / Delayed / 0.1-1.0
    vaginal bleeding / Delayed / 0.1-1.0
    urinary incontinence / Early / 0.1-1.0
    cystitis / Delayed / 0.1-1.0
    vaginitis / Delayed / 0.1-1.0
    impotence (erectile dysfunction) / Delayed / 0.1-1.0
    ejaculation dysfunction / Delayed / 0.1-1.0
    dysuria / Early / 0.1-1.0
    dehydration / Delayed / 0.1-1.0
    choreoathetosis / Delayed / 0-0.1
    delirium / Early / 0-0.1
    aphasia / Delayed / 0-0.1
    neuropathic pain / Delayed / 0-0.1
    euphoria / Early / 0-0.1
    melena / Delayed / 0-0.1
    glossitis / Early / 0-0.1
    angina / Early / 0-0.1
    psoriasis / Delayed / 0-0.1
    glycosuria / Early / 0-0.1
    hemolysis / Early / 0-0.1
    thrombocytopenia / Delayed / 0-0.1
    hypokalemia / Delayed / 0-0.1
    gout / Delayed / 0-0.1
    dyspnea / Early / 1.0
    dysphemia / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    priapism / Early / Incidence not known
    leukopenia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hostility / Early / Incidence not known
    infertility / Delayed / Incidence not known
    urinary retention / Early / Incidence not known
    galactorrhea / Delayed / Incidence not known

    Mild

    drowsiness / Early / 18.0-57.0
    xerostomia / Early / 7.0-44.0
    weight gain / Delayed / 8.0-23.0
    headache / Early / 17.0-21.0
    agitation / Early / 6.0-20.0
    dizziness / Early / 9.0-18.0
    fatigue / Early / 3.0-14.0
    appetite stimulation / Delayed / 2.0-12.0
    asthenia / Delayed / 2.0-10.0
    nausea / Early / 7.0-8.0
    vomiting / Early / 1.0-8.0
    dyspepsia / Early / 2.0-7.0
    abdominal pain / Early / 4.0-7.0
    pharyngitis / Delayed / 4.0-6.0
    lethargy / Early / 1.0-5.0
    nasal congestion / Early / 3.0-5.0
    back pain / Delayed / 2.0-5.0
    irritability / Delayed / 1.0-4.0
    anxiety / Delayed / 2.0-4.0
    rash / Early / 4.0-4.0
    rhinitis / Early / 3.0-4.0
    arthralgia / Delayed / 1.0-4.0
    paresthesias / Delayed / 2.0-3.0
    cough / Delayed / 3.0-3.0
    syncope / Early / 2.0-2.0
    restless legs syndrome (RLS) / Delayed / 2.0-2.0
    hypoesthesia / Delayed / 2.0-2.0
    vertigo / Early / 0.1-2.0
    restlessness / Early / 1.0-2.0
    gastroesophageal reflux / Delayed / 2.0-2.0
    acne vulgaris / Delayed / 2.0-2.0
    hyperhidrosis / Delayed / 2.0-2.0
    infection / Delayed / 2.0-2.0
    sinusitis / Delayed / 2.0-2.0
    fever / Early / 1.0-2.0
    otalgia / Early / 1.0-2.0
    musculoskeletal pain / Early / 2.0-2.0
    myalgia / Early / 2.0-2.0
    libido decrease / Delayed / 0-2.0
    hyperkinesis / Delayed / 0.1-1.0
    weight loss / Delayed / 0.1-1.0
    paranoia / Early / 0.1-1.0
    flatulence / Early / 0.1-1.0
    gingivitis / Delayed / 0.1-1.0
    dysgeusia / Early / 0.1-1.0
    dental caries / Delayed / 0.1-1.0
    seborrhea / Delayed / 0.1-1.0
    pruritus / Rapid / 0.1-1.0
    maculopapular rash / Early / 0.1-1.0
    epistaxis / Delayed / 0.1-1.0
    ecchymosis / Delayed / 0.1-1.0
    leukocytosis / Delayed / 0.1-1.0
    ocular pain / Early / 0.1-1.0
    xerophthalmia / Early / 0.1-1.0
    tinnitus / Delayed / 0.1-1.0
    pelvic pain / Delayed / 0.1-1.0
    amenorrhea / Delayed / 0.1-1.0
    increased urinary frequency / Early / 0.1-1.0
    dysmenorrhea / Delayed / 0.1-1.0
    breast discharge / Delayed / 0.1-1.0
    leukorrhea / Delayed / 0.1-1.0
    libido increase / Delayed / 0.1-1.0
    malaise / Early / 0.1-1.0
    photosensitivity / Delayed / 0.1-1.0
    chills / Rapid / 0.1-1.0
    emotional lability / Early / 0-0.1
    skin discoloration / Delayed / 0-0.1
    hiccups / Early / 0-0.1
    hyperventilation / Early / 0-0.1
    polyuria / Early / 0-0.1
    nocturia / Early / 0-0.1
    gynecomastia / Delayed / 0-0.1
    anorexia / Delayed / 1.0
    somnambulism / Early / Incidence not known
    nightmares / Early / Incidence not known
    polydipsia / Early / Incidence not known
    insomnia / Early / Incidence not known
    hypothermia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) Androgen deprivation therapy (e.g.,abarelix) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Of the androgen deprivation therapies, abarelix is associated with a known risk for QT prolongation. Quetiapine is associated with a possible risk for QT prolongation and torsade de pointes (TdP) and should not be used with agents having a known risk for QT prolongation.
    Acarbose: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Acetaminophen; Butalbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Acetaminophen; Butalbital; Caffeine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of central nervous system (CNS) depressants like quetiapine can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Drugs that can cause CNS depression, including dichloralphenazone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness if used concomitantly with atypical antipsychotics.
    Acetaminophen; Diphenhydramine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine.
    Acetaminophen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as quetiapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking quetiapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower quetiapine dose. Monitor patients for sedation and respiratory depression.
    Acetaminophen; Pentazocine: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
    Acetaminophen; Propoxyphene: (Moderate) The central nervous system (CNS) effects of propoxyphene and other CNS depressants are additive. Concomitant use of propoxyphene with other CNS depressants can potentiate respiratory depression and/or sedation.
    Acetaminophen; Tramadol: (Moderate) Due to the primary CNS effects of quetiapine, caution should be used when given in combination with other centrally acting medications, such as tramadol. Both of these medications can lower the seizure threshold when used alone, therefore there is an even greater risk when they are used concomitantly.
    Acetazolamide: (Moderate) Caution is advisable during concurrent use of quetiapine and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Aclidinium; Formoterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Albiglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Albuterol: (Minor) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Albuterol; Ipratropium: (Minor) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL 2 may affect CNS function significantly.Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity, such as quetiapine. Use with caution.
    Alfentanil: (Moderate) Concomitant use of alfentanil with other CNS depressants, including atypical antipsychotics, can potentiate the effects of alfentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Alfuzosin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), coadministration of alfuzosin and quetiapine should be avoided. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. Concurrent use may result in additive effects on the QT interval.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Alogliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alogliptin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alogliptin; Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alpha-glucosidase Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alprazolam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Amifampridine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Amiodarone: (Major) The concomitant use of amiodarone and quetiapine should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Amitriptyline; Chlordiazepoxide: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Amobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Amoxapine: (Moderate) Use caution during co-administration of amoxapine and quetiapine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Avoid concurrent use of quetiapine and clarithromycin due to the potential for additive effects on the QT interval and torsade de pointes (TdP) and the potential for greatly increased quetiapine exposure. Clarithromycin is a potent inhibitor of CYP3A4 that is expected to signficantly reduce metabolism of quetiapine. If administration of clarithromycin is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. Monitor for quetiapine-related side effects. If clarithromycin is discontinued, increase the quetiapine dose by 6-fold. Clarithromycin has an established causal association with QT prolongation and TdP (torsade de pointes). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concurrent use of quetiapine and clarithromycin due to the potential for additive effects on the QT interval and torsade de pointes (TdP) and the potential for greatly increased quetiapine exposure. Clarithromycin is a potent inhibitor of CYP3A4 that is expected to signficantly reduce metabolism of quetiapine. If administration of clarithromycin is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. Monitor for quetiapine-related side effects. If clarithromycin is discontinued, increase the quetiapine dose by 6-fold. Clarithromycin has an established causal association with QT prolongation and TdP (torsade de pointes). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Amprenavir: (Moderate) The cytochrome P450 3A4 (CYP3A4) isoenzyme is involved in the metabolism of quetiapine. Anti-retroviral protease inhibitors, such as amprenavir, may increase plasma concentrations of quetiapine through CYP3A4 inhibition. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include quetiapine.
    Anticholinergics: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Apalutamide: (Major) Increase the dose of quetiapine by up to 5-fold if coadministration with apalutamide is necessary. If apalutamide is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold.
    Apomorphine: (Major) Concurrent use of quetiapine and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. QT prolongation is also possible with apomorphine administration. The change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines; however with higher doses, large increases (> 60 msecs from pre-dose) have occurred. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended. Additionally, antipsychotics (e.g., quetiapine) may compromise the effectiveness of apomorphine by blocking its dopamine agonist properties.
    Aprepitant, Fosaprepitant: (Major) Use caution if quetiapine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in quetiapine-related adverse effects, including QT prolongation and torsade de pointes (TdP), for several days after administration of a multi-day aprepitant regimen. Quetiapine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of quetiapine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Arformoterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Aripiprazole: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Quetiapine is an atypical antipsychotics with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with aripiprazole. In addition, caution is advisable when aripiprazole is given in combination with other CNS depressants such as other atypical antipsychotics. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, tardive dyskinesia, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent.
    Arsenic Trioxide: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with quetiapine include arsenic trioxide.
    Artemether; Lumefantrine: (Major) Concurrent use of quetiapine and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if quetiapine must be used with or after artemether; lumefantrine treatment. Administration of artemether; lumefantrine is associated with prolongation of the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Asenapine: (Major) Avoid coadministration of asenapine and quetiapine. Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Asenapine has been associated with QT prolongation.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of central nervous system (CNS) depressants like quetiapine can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as quetiapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking quetiapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower quetiapine dose. Monitor patients for sedation and respiratory depression.
    Atazanavir: (Major) Avoid concurrent use of quetiapine and anti-retroviral protease inhibitors, such as atazanavir. Atazanavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of atazanavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If atazanavir is discontinued, increase the quetiapine dose by 6-fold.
    Atazanavir; Cobicistat: (Major) Avoid concurrent use of quetiapine and anti-retroviral protease inhibitors, such as atazanavir. Atazanavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of atazanavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If atazanavir is discontinued, increase the quetiapine dose by 6-fold. (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
    Atenolol; Chlorthalidone: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include quetiapine.
    Atropine: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Atropine; Difenoxin: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Atropine; Diphenoxylate: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Atropine; Edrophonium: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects. (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Azelastine; Fluticasone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Azilsartan; Chlorthalidone: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Azithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering quetiapine with azithromycin. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Additionally, azithromycin has been associated with cases of QT prolongation and TdP, reported during the post-marketing period.
    Barbiturates: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Beclomethasone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Bedaquiline: (Major) Concurrent use of quetiapine and bedaquiline should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects. (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Belladonna; Opium: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Bendroflumethiazide; Nadolol: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with quetiapine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking quetiapine, reduce initial dosage and titrate to clinical response. If quetiapine is initiated a patient taking an opioid agonist, use a lower initial dose of quetiapine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Benztropine: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Betamethasone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include quetiapine.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include quetiapine.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Boceprevir: (Major) Coadministration of boceprevir, a potent CYP3A4 inhibitor, with quetiapine, a CYP3A4 substrate, may result in increased exposure to quetiapine. If administration of boceprevir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If boceprevir is discontinued, increase the quetiapine dose by 6-fold.
    Bosentan: (Moderate) Bosentan is a CYP3A4 inducer and may increase the metabolism and decrease the serum concentration of quetiapine if coadministered. Increased doses of quetiapine may be required for control of psychotic symptoms when a hepatic enzyme inducer like bosentan is administered concurrently.
    Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as quetiapine. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary.
    Brigatinib: (Moderate) Monitor for a decrease in the efficacy of quetiapine if coadministration with brigatinib is necessary. Quetiapine is a sensitive CYP3A4 substrate. At clinically relevant concentrations, brigatinib induced CYP3A via activation of the pregnane X receptor (PXR); this may decrease concentrations of sensitive CYP3A substrates.
    Bromocriptine: (Moderate) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the atypical antipsychotics. The atypical antipsychotics elevate prolactin to various degrees. Like other drugs that antagonize dopamine D2 receptors, the elevation in prolactin from atypical antipsychotics can persist during chronic administration. Monitor the patient for reduced response to bromocriptine. Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
    Brompheniramine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Budesonide: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Budesonide; Formoterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Buprenorphine: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of quetiapine and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Quetiapine has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of quetiapine and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of quetiapine and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Quetiapine has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of quetiapine and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buspirone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Butabarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Butorphanol: (Moderate) Concomitant use of butorphanol with quetiapine can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a centrally acting medication needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
    Cabergoline: (Major) The prolactin-lowering effect of cabergoline may be antagonized by medications that increase prolactin levels such as the antipsychotic drugs. In addition, cabergoline is a dopamine agonist and may diminish the effectiveness of dopamine antagonists such as the antipsychotics.
    Canagliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Canagliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and atypical antipsychotics. CNS depressants can potentiate the effects of cannabidiol.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Carbamazepine: (Major) Coadministration of carbamazepine, a potent CYP3A4 inducer, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Additionally, case reports indicate that quetiapine, when started after carbamazepine therapy, may lead to elevated concentrations of carbamazepine-10,11-epoxide (CBZ-E), the active metabolite of carbamazepine. In each case, the CBZ-E:carbamazepine ratio increased 3- to 4-fold. After discontinuation of quetiapine or substitution of oxcarbazepine for carbamazepine, CBZ-E and carbamazepine concentrations returned to baseline. The mechanism of this interaction may be inhibition of epoxide hydrolase and/or CBZ-diol glucuronidation by quetiapine. CBZ-E is known to have neurotoxic properties; one patient receiving quetiapine concurrently with carbamazepine experienced ataxia and agitation. The clinician should consider monitoring CBZ-E concentrations if quetiapine is added to carbamazepine therapy.
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbidopa; Levodopa: (Moderate) Levodopa is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of levodopa. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior. Certain atypical antipsychotics, such as quetiapine or pimavanserin, may be preferable to other antipsychotics in these patients.
    Carbidopa; Levodopa; Entacapone: (Moderate) Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of the COMT inhibitors (e.g., entacapone, tolcapone). In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior. (Moderate) Levodopa is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of levodopa. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior. Certain atypical antipsychotics, such as quetiapine or pimavanserin, may be preferable to other antipsychotics in these patients.
    Carbinoxamine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Cariprazine: (Moderate) The risk of adverse effects may be increased during concurrent use of cariprazine with other antipsychotics, such as quetiapine. Similar to other antipsychotics, cariprazine administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. The incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, but the risk appears to be increased.
    Ceritinib: (Major) Avoid coadministration of ceritinib with quetiapine due to an increased risk for QT prolongation. Systemic exposure of quetiapine may also be increased resulting in increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Limited data, including some case reports, suggest that quetiapine, a sensitive CYP3A4 substrate, may also be associated with a significant prolongation of the QTc interval in rare instances. Coadministration with another strong CYP3A4 inhibitor significantly increased quetiapine exposure; the manufacturer recommends a large dose reduction when coadministered with strong CYP3A4 inhibitors that do not cause QT prolongation.
    Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Cetrorelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs including cetrorelix.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chloramphenicol: (Major) Coadministration of chloramphenicol, a potent CYP3A4 inhibitor, with quetiapine, a CYP3A4 substrate, may result in increased exposure to quetiapine. If administration of chloramphenicol is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If chloramphenicol is discontinued, increase the quetiapine dose by 6-fold.
    Chlorcyclizine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlordiazepoxide: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Chlordiazepoxide; Clidinium: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects. (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Chloroquine: (Major) Concurrent use of quetiapine and chloroquine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). The need to coadminister these drugs should be done with a careful assessment of risks versus benefits. Chloroquine administration is associated with an increased risk of QT prolongation and TdP. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Chlorothiazide: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Chlorpheniramine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Dextromethorphan: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of central nervous system (CNS) depressants like quetiapine can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of central nervous system (CNS) depressants like quetiapine can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Chlorpromazine: (Major) Concurrent use of quetiapine and chlorpromazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Chlorthalidone: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Chlorthalidone; Clonidine: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine. (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may be induced or exacerbated in patients receiving concomitant clonidine and antipsychotics. Caution patients to avoid hazardous tasks, such as driving or operating machinery, until the effects of concurrent use are known. Also, based on observations in patients in a state of alcoholic delirium, it has been suggested that high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
    Chlorzoxazone: (Moderate) Additive CNS depression is possible if chlorzoxazone is used concomitantly with other CNS depressants including quetiapine. Additive effects of sedation and dizziness can occur, which can impair the ability to undertake tasks requiring mental alertness. Dosage adjustments of one or both medications may be necessary.
    Ciclesonide: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Cimetidine: (Minor) Cimetidine may cause a decrease in quetiapine clearance. Although it is not usually necessary to adjust the dose of quetiapine when cimetidine is coadministered, patients should be monitored for a potential increase in the pharmacologic effects of quetiapine.
    Ciprofloxacin: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. If possible, avoid use of quetiapine with other agents associated with a possible risk for QT prolongation and torsade de pointes, including ciprofloxacin
    Cisapride: (Severe) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Because of the potential for torsade de pointes (TdP), use of cisapride with quetiapine is contraindicated.
    Citalopram: (Major) Concurrent use of quetiapine and citalopram should be avoided if possible. Citalopram causes dose-dependent QT interval prolongation and quetiapine is associated with a risk for QT prolongation and torsade de pointes (TdP). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. However, if concurrent therapy is considered essential, ECG monitoring is recommended.
    Clarithromycin: (Major) Avoid concurrent use of quetiapine and clarithromycin due to the potential for additive effects on the QT interval and torsade de pointes (TdP) and the potential for greatly increased quetiapine exposure. Clarithromycin is a potent inhibitor of CYP3A4 that is expected to signficantly reduce metabolism of quetiapine. If administration of clarithromycin is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. Monitor for quetiapine-related side effects. If clarithromycin is discontinued, increase the quetiapine dose by 6-fold. Clarithromycin has an established causal association with QT prolongation and TdP (torsade de pointes). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Clemastine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Clobazam: (Moderate) Benzodiazepines such as clobazam should be combined cautiously with antipsychotics because of the potential for additive CNS depressant effects, and reduced effectiveness of clobazam as an anticonvulsant due to the possible lowering of the seizure threshold by antipsychotics.
    Clofazimine: (Major) Avoid coadministration of clofazimine and quetiapine due to the potential for additive QT prolongation. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Clonazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Clonidine: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may be induced or exacerbated in patients receiving concomitant clonidine and antipsychotics. Caution patients to avoid hazardous tasks, such as driving or operating machinery, until the effects of concurrent use are known. Also, based on observations in patients in a state of alcoholic delirium, it has been suggested that high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
    Clozapine: (Major) Concurrent use of quetiapine and clozapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with clozapine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Cobicistat: (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
    Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Codeine; Phenylephrine; Promethazine: (Major) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Due to the risk of additive QT prolongation and potential for serious arrhythmias, avoid co-use with quetiapine if possible. In addition, co-administration of promethazine with antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from these combinations has not been established and data are very limited, the risk appears to be increased during combined use versus use of an antipsychotic alone. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Codeine; Promethazine: (Major) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Due to the risk of additive QT prolongation and potential for serious arrhythmias, avoid co-use with quetiapine if possible. In addition, co-administration of promethazine with antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from these combinations has not been established and data are very limited, the risk appears to be increased during combined use versus use of an antipsychotic alone. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    COMT inhibitors: (Moderate) Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of the COMT inhibitors (e.g., entacapone, tolcapone). In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior.
    Conivaptan: (Major) Coadministration of conivaptan, a potent CYP3A4 inhibitor, with quetiapine may result in increased exposure to quetiapine, a CYP3A4 substrate. The manufacturer of conivaptan recommends avoiding concomitant use of conivaptan with drugs that are primarily metabolized by CYP3A4. Subsequent treatment with CYP3A substrates, such as quetiapine, may be initiated no sooner than 1 week after completion of conivaptan therapy. The quetiapine manufacturer recommends reducing the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events when combined with a potent CYP3A4 inhibitor. If the CYP3A4 inhibitor is discontinued, increase the quetiapine dose by 6-fold.
    Corticosteroids: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Corticotropin, ACTH: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Cortisone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Crizotinib: (Major) Avoid coadministration of crizotinib with quetiapine due to the risk of QT prolongation. Crizotinib has been associated with concentration-dependent QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Cyproheptadine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Dabrafenib: (Major) The concomitant use of dabrafenib and quetiapine may lead to decreased quetiapine concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of quetiapine efficacy. Dabrafenib is a moderate CYP3A4 inducer and quetiapine is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
    Dantrolene: (Moderate) Simultaneous use of dantrolene and other CNS depressants such as antipsychotics can increase CNS depression (e.g., drowsiness).
    Dapagliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Dapagliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Dapagliflozin; Saxagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Darifenacin: (Moderate) When coadministering quetiapine and darifenacin, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents such as darifenacin. Constipation may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro binding affinity for several muscarinic receptor subtypes.
    Darunavir: (Major) Avoid concurrent use of quetiapine and darunavir. Darunavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If coadministration is required, reduce the quetiapine dose to one-sixth of the current dose and monitor for quetiapine-related adverse events. If darunavir is discontinued, increase the quetiapine dose by 6-fold.
    Darunavir; Cobicistat: (Major) Avoid concurrent use of quetiapine and darunavir. Darunavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If coadministration is required, reduce the quetiapine dose to one-sixth of the current dose and monitor for quetiapine-related adverse events. If darunavir is discontinued, increase the quetiapine dose by 6-fold. (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concurrent use of quetiapine and darunavir. Darunavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If coadministration is required, reduce the quetiapine dose to one-sixth of the current dose and monitor for quetiapine-related adverse events. If darunavir is discontinued, increase the quetiapine dose by 6-fold. (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of strong CYP3A4 inhibitors, such as ritonavir. When ritonavir is discontinued, the dose should be increased by 6-fold. The plasma concentrations of quetiapine may be elevated when administered concurrently with ritonavir.
    Dasatinib: (Major) Avoid coadministration of dasatinib and quetiapine due to the potential for QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Deflazacort: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Degarelix: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like quetiapine. In addition, quetiapine may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Delavirdine: (Major) If coadministration is required, reduce the quetiapine dose to one sixth of the current dose and monitor for adverse events. Delavirdine is expected to significantly increase exposure to quetiapine. Delavirdine is a potent CYP3A4 inhibitor and quetiapine is a CYP3A4 substrate. If delavirdine is discontinued, increase the quetiapine dose by 6-fold.
    Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with quetiapine. Halogenated anesthetics can prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Deutetrabenazine: (Major) Avoid coadministration of deutetrabenazine with quetiapine. Clinically relevant QT prolongation may occur with deutetrabenazine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Additionally, deutetrabenazine is a reversible, dopamine depleting drug and quetiapine is a dopamine antagonist. The risk for parkinsonism, neuroleptic malignant syndrome (NMS), and akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as quetiapine, may have additive effects and worsen drowsiness or sedation.
    Dexamethasone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Dexchlorpheniramine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Dexmethylphenidate: (Moderate) Atypical antipsychotics and dexmethylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Dexmethylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of dexmethylphenidate.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Dextromethorphan; Promethazine: (Major) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Due to the risk of additive QT prolongation and potential for serious arrhythmias, avoid co-use with quetiapine if possible. In addition, co-administration of promethazine with antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from these combinations has not been established and data are very limited, the risk appears to be increased during combined use versus use of an antipsychotic alone.
    Dextromethorphan; Quinidine: (Major) Quetiapine should be used cautiously and with close monitoring with quinidine. Quinidine is associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Diazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Dicyclomine: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of central nervous system (CNS) depressants like quetiapine can potentiate the effects of dihydrocodeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses.
    Diltiazem: (Moderate) The cytochrome P450 3A4 (CYP3A4) isoenzyme is involved in the metabolism of quetiapine. Diltiazem may increase plasma concentrations of quetiapine through CYP3A4 inhibition. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
    Dimenhydrinate: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Diphenhydramine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Diphenhydramine; Ibuprofen: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Diphenhydramine; Naproxen: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Diphenhydramine; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Disopyramide: (Major) Quetiapine should be used cautiously and with close monitoring with disopyramide. Disopyramide is associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Additive anticholinergic effects are also possible with disopyramide, as both quetiapine and disopyramide exhibit significant anticholinergic activity.
    Dofetilide: (Major) Coadministration of dofetilide and quetiapine is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Dolasetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), coadministration of dolasetron and quetiapine should be avoided. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Concurrent use may further increase the risk for QT prolongation.
    Dolutegravir; Rilpivirine: (Major) Concurrent use of quetiapine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include quetiapine.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include quetiapine.
    Dopamine: (Major) Antipsychotic agents may inhibit the clinical antiparkinsonian response to therapy by blocking dopamine receptors in the brain. Quetiapine may also cause additive sedation with drugs like dopamine. In general, however, atypical antipsychotics like quetiapine are less likely to interfere with these therapies than traditional antipsychotic agents.
    Doxylamine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Doxylamine; Pyridoxine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Dronabinol: (Moderate) Drugs that can cause CNS depression such as dronabinol, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Dronedarone: (Severe) Concomitant use of dronedarone and quetiapine is contraindicated. Dronedarone is an inhibitor of CYP3A. Quetiapine is a substrate for CYP3A4. Coadministration of dronedarone and quetiapine may result in elevated plasma concentrations of quetiapine. In addition, quetiapine has been established to have a possible risk for QT prolongation and Torsade de Pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with quetiapine include droperidol.
    Dulaglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Duloxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with drugs that are dopamine antagonists such as quetiapine. Patients receiving quetiapine and an SNRI should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Duvelisib: (Moderate) Monitor for increased toxicity of quetiapine if coadministered with duvelisib. Coadministration may increase the exposure of quetiapine. Quetiapine is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
    Efavirenz: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval, such as efavirenz. In addition, efavirenz may induce the CYP3A4 metabolism of quetiapine, and thus, decrease the serum concentration of quetiapine.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval, such as efavirenz. In addition, efavirenz may induce the CYP3A4 metabolism of quetiapine, and thus, decrease the serum concentration of quetiapine.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval, such as efavirenz. In addition, efavirenz may induce the CYP3A4 metabolism of quetiapine, and thus, decrease the serum concentration of quetiapine.
    Elbasvir; Grazoprevir: (Moderate) Administering quetiapine with elbasvir; grazoprevir may result in elevated quetiapine plasma concentrations. Quetiapine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Elexacaftor; tezacaftor; ivacaftor: (Moderate) Use caution when administering ivacaftor and quetiapine concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as quetiapine, can increase quetiapine exposure leading to increased or prolonged therapeutic effects and adverse events.
    Eliglustat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include quetiapine.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
    Empagliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Empagliflozin; Linagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Empagliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concurrent use of quetiapine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Concurrent use of quetiapine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Encorafenib: (Major) Avoid coadministration of encorafenib and quetiapine due to the potential for additive QT prolongation. Concurrent use may also result in increased toxicity or decreased efficacy of quetiapine. Encorafenib is associated with dose-dependent prolongation of the QT interval. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established. Limited data, including some case reports, suggest that quetiapine, a sensitive CYP3A4 substrate, may be associated with a significant prolongation of the QTc interval in rare instances.
    Enflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with quetiapine. Halogenated anesthetics can prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Entacapone: (Moderate) Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of the COMT inhibitors (e.g., entacapone, tolcapone). In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior.
    Entrectinib: (Major) Avoid coadministration of entrectinib with quetiapine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Enzalutamide: (Major) Increase the dose of quetiapine by up to 5-fold if coadministration with enzalutamide is necessary. If enzalutamide is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Eribulin: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval, such as eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Ertugliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ertugliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ertugliflozin; Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Erythromycin: (Major) Erythromycin has an established causal association with QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase QT interval. In addition, CYP3A4 is involved in the metabolism of quetiapine. Erythromycin may increase plasma concentrations of quetiapine through CYP3A4 inhibition. Coadministration of with erythromycin resulted in decreased quetiapine clearance, increased quetiapine plasma concentrations, and prolonged quetiapine half-life. Nineteen patients received quetiapine (200 mg PO twice a day) for roughly 7 days, then erythromycin (500 mg PO 3 times a day) was added for 5 days. Mean quetiapine AUC increased 129% (range 15 to 300%) and the half-life was elevated from 7 to 16 hours. Pharmacokinetic changes of this magnitude will most likely increase the incidence of adverse events, such as drowsiness, orthostatic hypotension, xerostomia, and dizziness. The manufacturer of quetiapine recommends a reduced dose during concurrent administration of CYP3A4 inhibitors. Macrolides that do not inhibit CYP3A4, such as azithromycin and dirithromycin, should be considered in patients taking quetiapine.
    Erythromycin; Sulfisoxazole: (Major) Erythromycin has an established causal association with QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase QT interval. In addition, CYP3A4 is involved in the metabolism of quetiapine. Erythromycin may increase plasma concentrations of quetiapine through CYP3A4 inhibition. Coadministration of with erythromycin resulted in decreased quetiapine clearance, increased quetiapine plasma concentrations, and prolonged quetiapine half-life. Nineteen patients received quetiapine (200 mg PO twice a day) for roughly 7 days, then erythromycin (500 mg PO 3 times a day) was added for 5 days. Mean quetiapine AUC increased 129% (range 15 to 300%) and the half-life was elevated from 7 to 16 hours. Pharmacokinetic changes of this magnitude will most likely increase the incidence of adverse events, such as drowsiness, orthostatic hypotension, xerostomia, and dizziness. The manufacturer of quetiapine recommends a reduced dose during concurrent administration of CYP3A4 inhibitors. Macrolides that do not inhibit CYP3A4, such as azithromycin and dirithromycin, should be considered in patients taking quetiapine.
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as quetiapine, should be done with caution and close monitoring. In addition, because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering escitalopram with drugs that are dopamine antagonists such as atypical antipsychotics. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving escitalopram and atypical antipsychotics should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Esketamine: (Major) Closely monitor patients receiving esketamine and quetiapine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Eslicarbazepine: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4 thereby having the potential to lower the plasma levels of medications metabolized through these pathways. The effectiveness of CNS medications such as quetiapine could theoretically be decreased.
    Estazolam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as antipsychotics, to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Antipsychotics with a higher incidence of sedation, such as olanzapine, clozapine, quetiapine, lurasidone, chlorpromazine, and thioridazine, are more likely to interact with eszopiclone. In one evaluation, concurrent use of eszopiclone and olanzapine reduced psychomotor function as measured by the Digit Symbol Substitution Test (DSST).
    Ethanol: (Moderate) Alcohol may potentiate the CNS effects of the atypical antipsychotics, which have the potential to cause increased sedation, or to impair judgment, thinking, or motor skills. Patients should be appropriately cautioned.
    Exenatide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ezogabine: (Major) Ezogabine has been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with ezogabine include quetiapine.
    Fentanyl: (Moderate) Concomitant use of fentanyl with other central nervous system (CNS) depressants such as quetiapine can potentiate the effects of fentanyl and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of fentanyl in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of fentanyl and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Fesoterodine: (Moderate) When coadministering quetiapine and fesoterodine, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents such as fesoterodine. Constipation may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, an active metabolite of quetiapine which has demonstrated a moderate to strong in vitro binding affinity for several muscarinic receptor subtypes.
    Fingolimod: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. If coadministration is necessary, after the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flavoxate: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Flecainide: (Major) Concurrent use of quetiapine and flecainide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; although, the increase in QT interval is largely due to prolongation of the QRS interval. Causality for TdP has not been established for flecainide.
    Fluconazole: (Severe) Concurrent use of fluconazole and quetiapine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Fluconazole is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quetiapine. These drugs used in combination may result in elevated quetiapine plasma concentrations, causing an increased risk for quetiapine-related adverse events, such as QT prolongation. Additionally, fluconazole has been associated with prolongation of the QT interval; do not use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quetiapine.
    Fludrocortisone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Flunisolide: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Fluoxetine: (Major) Avoid use together if possible. Coadministration may increase the risk for QT prolongation and torsade de pointes. Caution is also advised since both drugs act on the CNS. If use together is necessary, consider using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status. According to the manufacturer of quetiapine, other drugs having an association with QT prolongation should not be used with quetiapine. QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of fluoxetine. The manufacturer of fluoxetine recommends caution with combined use. The effects of fluoxetine on interacting drugs may persist for several weeks after discontinuation of fluoxetine because of its long elimination half-life. In a study conducted by the manufacturer, concurrent use of 60 mg/day of fluoxetine and 300 mg twice daily of quetiapine did not alter the pharmacokinetics of quetiapine.
    Fluoxetine; Olanzapine: (Major) Avoid use together if possible. Coadministration may increase the risk for QT prolongation and torsade de pointes. Caution is also advised since both drugs act on the CNS. If use together is necessary, consider using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status. According to the manufacturer of quetiapine, other drugs having an association with QT prolongation should not be used with quetiapine. QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of fluoxetine. The manufacturer of fluoxetine recommends caution with combined use. The effects of fluoxetine on interacting drugs may persist for several weeks after discontinuation of fluoxetine because of its long elimination half-life. In a study conducted by the manufacturer, concurrent use of 60 mg/day of fluoxetine and 300 mg twice daily of quetiapine did not alter the pharmacokinetics of quetiapine. (Major) Concurrent use of quetiapine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that both olanzapine and quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with olanzapine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Fluphenazine: (Moderate) Concurrent use of quetiapine and fluphenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Flurazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Fluticasone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Fluticasone; Salmeterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Fluticasone; Vilanterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation, torsade de pointes (TdP), and elevated quetiapine concentrations during concurrent use of fluvoxamine and quetiapine. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. The manufacturer of quetiapine recommends avoiding combined use of quetiapine with drugs known to increase the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, fluvoxamine is a moderate CYP3A4 inhibitor and may decrease the clearance of CYP3A4 substrates such as quetiapine. Decreased metabolism of quetiapine may lead to adverse effects such as orthostatic hypotension, sedation, QT prolongation, or extrapyramidal symptoms.
    Food: (Major) It is recommended that patients avoid the use of marijuana, by any route, if they are treated for a psychiatric history, including psychosis and bipolar disorder, as the cannabinoids (the psychoactive ingredients, such as THC) in marijuana can produce psychotoxic effects and may exacerbate psychiatric disorders. A high frequency of use and use of products with high-potency of THC are potential risk factors for psychiatric effects. Additionally, additive CNS effects, such as sedation or CNS depression are possible. Clinical studies suggest that cannabis use may reduce the efficacy of some antipsychotic drugs. In addition, several cannabinoids in marijuana appear to influence the activity of CYP enzymes and P-glycoprotein, which may alter the concentrations of antipsychotics and influence either safety or efficacy, For example, the smoking of marijuana influences the metabolism of some medications in a manner similar to tobacco by inducing CYP1A2.
    Formoterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Formoterol; Mometasone: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Fosamprenavir: (Major) Avoid concurrent use of quetiapine, a CYP3A4 substrate, and fosamprenavir, a potent CYP3A4 inhibitor, due to the potential for increased exposure to quetiapine. If administration of fosamprenavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. If fosamprenavir is discontinued, increase the quetiapine dose by 6-fold.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as quetiapine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Fosphenytoin: (Major) Increased doses of quetiapine may be required for control of psychotic symptoms when fosphenytoin (which is metabolized to phenytoin) is administered concurrently. Coadministration of phenytoin (100 mg three times daily) and quetiapine (250 mg three times daily) increased the clearance of quetiapine by 5-fold. Chronic administration (7 to 14 days) of a potent CYP3A4 inducer, such as fosphenytoin, with quetiapine may require increases of the quetiapine dosage of up to 5-fold of the original dose. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Use quetiapine cautiously in patients with a history of seizures or with conditions that may lower the seizure threshold.
    Gabapentin: (Moderate) Antipsychotics that may enhance the CNS depressive effects of gabapentin, such as drowsiness or dizziness, include quetiapine. Patients should limit activity until they are aware of how coadministration affects them.
    Ganirelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to ganirelix, a gonadotropin-releasing hormone (GnRH) analog.
    Gemifloxacin: (Major) Concurrent use of quetiapine and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Gemifloxacin may also prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab ozogamicin with quetiapine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Gilteritinib: (Major) Avoid concomitant use of quetiapine with gilteritinib due to the potential for additive QT prolongation. Gilteritinib has been associated with QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Glasdegib: (Major) Avoid coadministration of glasdegib with quetiapine due to the potential for additive QT prolongation. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Glipizide; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Glyburide; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Glycopyrrolate: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Glycopyrrolate; Formoterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Goserelin: (Major) Avoid coadministration of quetiapine with goserelin due to the risk of QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
    Granisetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of granisetron and quetiapine should be avoided if possible. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron with drugs known to prolong the QT interval or are arrhythmogenic, may result in clinical consequences. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to its manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine.
    Halofantrine: (Major) Avoid use together. Coadministration increases the risk for QT prolongation and torsade de pointes (TdP). Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation. Consider alternative therapies. Halofantrine prolongs the QTc interval at normal therapeutic doses and has been reported to cause serious ventricular arrhythmias, sometimes associated with death. Quetiapine may rarely be associated with significant prolongation of the QTc interval.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with quetiapine. Halogenated anesthetics can prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Haloperidol: (Major) Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs that have established causal association with QT prolongation and TdP (torsade de pointes), like haloperidol. Coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Halothane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with quetiapine. Halogenated anesthetics can prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Histrelin: (Major) Avoid coadministration of quetiapine with histrelin due to the risk of QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine. (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include quetiapine.
    Hydrocortisone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Hydromorphone: (Moderate) Concomitant use of hydromorphone with other central nervous system (CNS) depressants can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include quetiapine. Prior to concurrent use of hydromorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If hydromorphone is used concurrently with a CNS depressant, a reduced dosage of hydromorphone and/or the CNS depressant is recommended; start with one-third to one-half of the estimated hydromorphone starting dose when using hydromorphone extended-release tablets. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and quetiapine. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Hydroxyzine: (Major) Avoid coadministration of hydroxyzine and quetiapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including quetiapine. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Hyoscyamine: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as quetiapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking quetiapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower quetiapine dose. Monitor patients for sedation and respiratory depression.
    Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as quetiapine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quetiapine, a CYP3A substrate, as quetiapine toxicities may be significantly increased. If coadministration cannot be avoided, the manufacturer of quetiapine recommends reducing the dose of quetiapine to one sixth of the current dose in combination with a potent CYP3A4 inhibitor. When the CYP3A4 inhibitor is discontinued, the dose of quetiapine should be increased by 6-fold. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as quetiapine. Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Imatinib: (Moderate) The cytochrome P450 3A4 isoenzyme is involved in the metabolism of quetiapine. Imatinib, STI-571 may increase plasma concentrations of quetiapine through CYP3A4 inhibition. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
    Incretin Mimetics: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Indacaterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Indacaterol; Glycopyrrolate: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Indinavir: (Major) Avoid concurrent use of quetiapine and anti-retroviral protease inhibitors, such as indinavir. Indinavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of indinavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If indinavir is discontinued, increase the quetiapine dose by 6-fold.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with quetiapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Insulin Degludec; Liraglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Insulin Glargine; Lixisenatide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Insulins: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Iohexol: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Iopamidol: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Iopromide: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Ioversol: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with quetiapine may result in increased serum concentrations of quetiapine. Quetiapine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isocarboxazid: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Isoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with quetiapine. Halogenated anesthetics can prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks.
    Isoniazid, INH; Rifampin: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks.
    Isosulfan Blue: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Itraconazole: (Major) Avoid coadministration of itraconazole with quetiapine due to the potential for additive effects on the QT interval; increased exposure to quetiapine may also occur. Both quetiapine and itraconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of itraconazole (a potent CYP3A4 inhibitor) with quetiapine (a CYP3A4 substrate) may result in elevated quetiapine plasma concentrations and could increase the risk for adverse events, including QT prolongation. The manufacturer recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as itraconazole. When itraconazole is discontinued, the dose should be increased by 6-fold. Of note, once itraconazole is discontinued, plasma concentrations decrease to almost undetectable concentrations within 7 to 14 days. The decline in plasma concentrations may be even more gradual in patients with hepatic cirrhosis or who are receiving concurrent CYP3A4 inhibitors.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and quetiapine concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as quetiapine, can increase quetiapine exposure leading to increased or prolonged therapeutic effects and adverse events.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with quetiapine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Additionally, monitor for loss of efficacy of quetiapine during coadministration of ivosidenib; a quetiapine dose adjustment may be necessary. Quetiapine is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased quetiapine concentrations. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Kava Kava, Piper methysticum: (Major) Patients who are taking atypical antipsychotics should only use kava kava with prescriber approval and close monitoring. Additive sedation and CNS effects are possible, and inhibition of antipsychotic metabolism may occur. In addition, kava kava has been reported to inhibit many CYP isozymes (i.e., CYP1A2, 2C9, 2C19, 2D6, 3A4, and 4A9/11) and important pharmacokinetic interactions with CNS-active agents that undergo oxidative metabolism via these CYP isozymes are possible. Atypical antipsychotics are metabolized by various CYP isoenzymes and it is not yet documented if pharmacokinetic interactions occur with kava kava. At least 1 case report of a potential clinically significant interaction with kava kava and an atypical antipsychotic has been reported.
    Ketoconazole: (Major) Avoid coadministration of quetiapine and ketoconazole due to the potential for additive effects on the QT interval; increased exposure to quetiapine may also occur. If coadministration cannot be avoided, the dose of quetiapine should be reduced to one-sixth the original dose. Both quetiapine and ketoconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of ketoconazole (a potent CYP3A4 inhibitor) with quetiapine (a CYP3A4 substrate) results in elevated quetiapine plasma concentrations and an increased risk for adverse events, including QT prolongation. Ketoconazole reduced the oral clearance of quetiapine by 84% resulting in a 335% increase in quetiapine maximum plasma concentrations.
    Lapatinib: (Major) Avoid coadministration of quetiapine with lapatinib due to the risk of QT prolongation. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Lefamulin: (Major) Coadministration of lefamulin tablets is contraindicated with quetiapine due to increased quetiapine exposure which may result in QT prolongation and torsade de pointes (TdP). Avoid use of lefamulin injection with quetiapine. If coadministration of lefamulin injection cannot be avoided, ECG monitoring is recommended during treatment. Quetiapine is a sensitive CYP3A4 substrate that may be associated with a significant prolongation of the QTc interval in rare instances. Lefamulin is a CYP3A4 inhibitor that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with quetiapine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quetiapine; monitor for potential reduction in efficacy. Quetiapine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quetiapine; monitor for potential reduction in efficacy. Quetiapine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Moderate) Caution is advised when administering quetiapine with letermovir, as taking these drugs together may increase quetiapine concentration and risk for adverse events. Reduce the quetiapine dose to 1/6 the original dose in patients also receiving cyclosporine, because the magnitude of this interaction may be increased. If letermovir or cyclosporine are discontinued, the quetiapine dose should be increased by 6-fold. Quetiapine is a substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent administration with another strong CYP3A4 inhibitors decreased quetiapine clearance by 84%, thereby resulting in a 6.2-fold increase in quetiapine exposure (AUC).
    Leuprolide: (Major) Avoid coadministration of quetiapine with leuprolide due to the risk of QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Avoid coadministration of quetiapine with leuprolide due to the risk of QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Levalbuterol: (Minor) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Levodopa: (Moderate) Levodopa is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of levodopa. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior. Certain atypical antipsychotics, such as quetiapine or pimavanserin, may be preferable to other antipsychotics in these patients.
    Levofloxacin: (Major) Concurrent use of quetiapine and levofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Additionally, rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Levomethadyl: (Severe) Quetiapine may rarely be associated with significant prolongation of the QTc interval. Caution is advised when administering quetiapine with drugs having an established causal association with QT prolongation and torsade de pointes including levomethadyl.
    Levorphanol: (Moderate) Concomitant use of levorphanol with other CNS depressants such as quetiapine can potentiate the effects of levorphanol on respiration, blood pressure, and alertness. Severe hypotension, respiratory depression, profound sedation, or coma may occur. Prior to concurrent use of levorphanol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. When concomitant treatment with levorphanol with another CNS depressant is necessary, reduce the dose of 1 or both drugs. The initial dose of levorphanol should be reduced by approximately 50% or more when levorphanol is used with another drug that may depress respiration.
    Linagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Linagliptin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Liraglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Lithium: (Major) Quetiapine and lithium are associated with QT prolongation. Coadministration may increase the risk of QT prolongation; therefore, quetiapine and lithium should be coadministered with caution and close monitoring. Some atypical antipsychotics, including quetiapine, are indicated as adjunctive therapy to mood stabilizers such as lithium. However, it is advisable to monitor patients for neurotoxicity during co-administration. Neuroleptic malignant syndrome (NMS) has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. Additive extrapyramidal effects have also been noted. Early case reports described an encephalopathic syndrome consisting of delirium, tremulousness, dyskinesia, seizures, leukocytosis, weakness, hyperpyrexia, confusion, extrapyramidal symptoms, elevations in laboratory values (e.g., liver function tests, blood urea nitrogen, fasting blood sugar) and, in some cases, irreversible brain damage, during use of lithium and conventional antipsychotics, particularly haloperidol. Subsequent rare reports of NMS or NMS-like reactions have been described during co-administration of lithium and atypical antipsychotics (e.g., risperidone, olanzapine, clozapine). Following resolution of NMS, there are isolated instances of re-emergence of symptoms following re-initiation of lithium as monotherapy. Lithium may be a risk factor for antipsychotic-induced NMS; however, this hypothesis has not been confirmed. In many reported cases, confounding factors have been present (e.g., previous history of NMS, high dose therapy). The ability of antipsychotics alone to precipitate NMS and the rarity of the condition further complicate assessment of lithium as a risk factor.
    Lixisenatide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Lofexidine: (Major) Avoid coadministration of lofexidine and quetiapine due to the potential for additive QT prolongation. Monitor ECG if coadministration cannot be avoided. Additionally, monitor for excessive hypotension and sedation during coadministration as lofexidine can potentiate the effects of CNS depressants. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Long-acting beta-agonists: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loop diuretics: (Moderate) Caution is advisable during concurrent use of quetiapine and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Loperamide: (Major) Avoid coadministration of Loperamide and Quetiapine if possible. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Limited data suggest that quetiapine is associated with a significant prolongation of the QTc interval.
    Loperamide; Simethicone: (Major) Avoid coadministration of Loperamide and Quetiapine if possible. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Limited data suggest that quetiapine is associated with a significant prolongation of the QTc interval.
    Lopinavir; Ritonavir: (Major) Avoid concurrent use of quetiapine and lopinavir; ritonavir due to the potential for additive effects on the QT interval. Lopinavir; ritonavir is associated with QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. Lopinavir; ritonavir may also inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of lopinavir; ritonavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. If lopinavir; ritonavir is discontinued, increase the quetiapine dose by 6-fold. (Major) The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of strong CYP3A4 inhibitors, such as ritonavir. When ritonavir is discontinued, the dose should be increased by 6-fold. The plasma concentrations of quetiapine may be elevated when administered concurrently with ritonavir.
    Lorazepam: (Moderate) Quetiapine decreases lorazepam clearance by about 20%. Patients should be monitored for a potential increase in the pharmacologic effect of lorazepam when coadministered with quetiapine. Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with lorazepam may result in additive sedative effects.
    Lovastatin: (Moderate) In a published case, it has been hypothesized that the combination of lovastatin and quetiapine resulted in prolongation of the QTc interval. The suggested mechanism is competitive inhibition of the CYP3A4 isoenzyme leading to elevated quetiapine plasma concentrations. Both lovastatin and quetiapine are CYP3A4 substrates. The QTc interval returned to baseline when the lovastatin dose was reduced. The clinical significance and reproducibility of this interaction is unknown.
    Lovastatin; Niacin: (Moderate) In a published case, it has been hypothesized that the combination of lovastatin and quetiapine resulted in prolongation of the QTc interval. The suggested mechanism is competitive inhibition of the CYP3A4 isoenzyme leading to elevated quetiapine plasma concentrations. Both lovastatin and quetiapine are CYP3A4 substrates. The QTc interval returned to baseline when the lovastatin dose was reduced. The clinical significance and reproducibility of this interaction is unknown.
    Loxapine: (Major) Caution is advisable during concurrent use of loxapine and other antipsychotics. Loxapine use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may reduce the efficacy of quetiapine by decreasing its systemic exposure. When used in combination with chronic lumacaftor; ivacaftor treatment (i.e., more than 7 to 14 days), titrate the quetiapine dosage based on clinical response and tolerability. Patients taking strong CYP3A4 inducers may require up to 5-fold of the original quetiapine dose to achieve therapeutic efficacy. If lumacaftor; ivacaftor is subsequently discontinued, reduce the quetiapine to its original dose within 7 to 14 days of discontinuation. Quetiapine is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer.
    Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and quetiapine concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as quetiapine, can increase quetiapine exposure leading to increased or prolonged therapeutic effects and adverse events.
    Lurasidone: (Major) Similar to other antipsychotics, lurasidone administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The risk of these adverse effects may be increased during concurrent use of lurasidone with other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as quetiapine. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Maprotiline: (Major) Concurrent use of quetiapine and maprotiline should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation.
    Meclizine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
    Mefloquine: (Major) Concurrent use of quetiapine and mefloquine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. There is also evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
    Meglitinides: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Mepenzolate: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Meperidine: (Moderate) Hypotension, respiratory and/or CNS depression (e.g., profound sedation or coma) may occur if meperidine is used concomitantly with CNS depressants like quetiapine.
    Meperidine; Promethazine: (Major) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Due to the risk of additive QT prolongation and potential for serious arrhythmias, avoid co-use with quetiapine if possible. In addition, co-administration of promethazine with antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from these combinations has not been established and data are very limited, the risk appears to be increased during combined use versus use of an antipsychotic alone. (Moderate) Hypotension, respiratory and/or CNS depression (e.g., profound sedation or coma) may occur if meperidine is used concomitantly with CNS depressants like quetiapine.
    Mephobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including antipsychotics.
    Mesoridazine: (Severe) Quetiapine may rarely be associated with significant prolongation of the QTc interval. Caution is advised when administering quetiapine with drugs having an established causal association with QT prolongation and torsade de pointes including mesoridazine.
    Metaproterenol: (Minor) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Saxagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Methadone: (Major) Concurrent use of quetiapine and methadone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). The need to coadminister these drugs should be done with extreme caution and a careful assessment of treatment risks versus benefits. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Methadone is also considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses averaging approximately 400 mg/day in adult patients. In addition, concomitant use of methadone with another CNS depressant, such as quetiapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Methazolamide: (Moderate) Caution is advisable during concurrent use of quetiapine and methazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Methohexital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Methscopolamine: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Methyclothiazide: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Methylphenidate: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
    Methylprednisolone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Metoclopramide: (Severe) Concomitant use of metoclopramide and antipsychotics is contraindicated by the manufacturer of metoclopramide as the risk of extrapyramidal effects may be increased. Both metoclopramide and antipsychotics antagonize dopamine receptors, which can increase the risk of extrapyramidal effects, including tardive dyskinesia or other dystonic reactions. Additionally, because both antipsychotics and metoclopramide can cause sedation, seizures, or increased prolactin levels, it is possible that the risk of these effects may be increased during concurrent use.
    Metolazone: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Metronidazole: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include quetiapine.
    Midazolam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Midostaurin: (Major) Avoid the concomitant use of midostaurin and quetiapine; both drugs have been reported to increase the QT interval. If coadministration cannot be avoided, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Mifepristone: (Major) Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effect dose should always be used. In addition, the cytochrome P450 3A4 (CYP3A4) isoenzyme is involved in the metabolism of quetiapine. Mifepristone may increase plasma concentrations of quetiapine through CYP3A4 inhibition. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
    Miglitol: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and quetiapine. The manufacturer of quetiapine recommends avoiding combined use of quetiapine with drugs known to increase the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation. Because both mirtazapine and quetiapine can cause somnolence, monitoring for additive CNS depressant effects is recommended.
    Mitotane: (Major) Use caution if mitotane and quetiapine are used concomitantly. If quetiapine is used with chronic (> 7 to 10 days) mitotane treatment, increase the dose of quetiapine by up to 5-fold, based on clinical response and tolerability. When mitotane is discontinued, reduce the dose of quetiapine to the original level within 7 to 14 days. Mitotane is a strong CYP3A4 inducer and quetiapine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of quetiapine. Additionally, mitotane can cause sedation, lethargy, vertigo, and other CNS adverse reactions; additive CNS effects may occur initially when mitotane is given concurrently with quetiapine.
    Molindone: (Major) Close monitoring is advisable during concurrent use of molindone with other antipsychotics. Because molindone shares certain pharmacological properties with other antipsychotics, additive cardiac effects (e.g., hypotension), CNS effects (e.g., drowsiness), anticholinergic effects (e.g., constipation, xerostomia), extrapyramidal effects, neuroleptic malignant syndrome, or seizures may occur. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Mometasone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Monoamine oxidase inhibitors: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Morphine: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include quetiapine. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
    Morphine; Naltrexone: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include quetiapine. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
    Moxifloxacin: (Major) Concurrent use of quetiapine and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
    Nabilone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Nafarelin: (Moderate) Antipsychotics may cause hyperprolactinemia and should not be administered concomitantly with nafarelin since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
    Nalbuphine: (Moderate) Drugs that can cause CNS depression such as nalbuphine, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Nateglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Nefazodone: (Major) Nefazodone may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of nefazodone is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If nefazodone is discontinued, increase the quetiapine dose by 6-fold.
    Nelfinavir: (Major) Avoid concurrent use of quetiapine and nelfinavir. Nelfinavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of nelfinavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. If nelfinavir is discontinued, increase the quetiapine dose by 6-fold.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval, such as quetiapine. Additionally, nilotinib is a moderate inhibitor of CYP3A4 and quetiapine is a substrate of CYP3A4; administering these drugs together may result in increased quetiapine levels. If the use of quetiapine is necessary, hold nilotinib therapy. If these drugs are used together, consider a quetiapine dose reduction and monitor patients for toxicity (e.g., QT interval prolongation).
    Non-Ionic Contrast Media: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
    Norfloxacin: (Major) Concurrent use of quetiapine and norfloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Quinolones have also been associated with QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Octreotide: (Major) Avoid coadministration of quetiapine and octreotide due to the potential for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Major) Concurrent use of quetiapine and ofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Some quinolones, including ofloxacin, have also been associated with QT prolongation. Additionally, post-marketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Major) Concurrent use of quetiapine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that both olanzapine and quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with olanzapine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Olodaterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of strong CYP3A4 inhibitors, such as ritonavir. When ritonavir is discontinued, the dose should be increased by 6-fold. The plasma concentrations of quetiapine may be elevated when administered concurrently with ritonavir.
    Ondansetron: (Major) Avoid coadministration of ondansetron and quetiapine due to the risk of QT prolongation. Monitor ECG for evidence of QT prolongation if concurrent use cannot be avoided. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP).
    Oritavancin: (Moderate) Quetiapine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of quetiapine may be reduced if these drugs are administered concurrently.
    Osimertinib: (Major) Avoid coadministration of quetiapine with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, periodically monitor ECGs and electrolytes; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Concentration-dependent QTc prolongation has also occurred during clinical trials of osimertinib.
    Oxaliplatin: (Major) Avoid coadministration of quetiapine with oxaliplatin due to the risk of additive QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Oxazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Oxybutynin: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as quetiapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking quetiapine, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower quetiapine dose. Monitor patients for sedation and respiratory depression.
    Oxymorphone: (Moderate) Concomitant use of oxymorphone with other CNS depressants may produce additive CNS depressant effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants include quetiapine. Prior to concurrent use of oxymorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxymorphone, a reduced dosage of oxymorphone (1/3 to 1/2 of the usual dose) and/or the CNS depressant is recommended. If the extended-release oxymorphone tablets are used concurrently with a CNS depressant, it is recommended to use an initial dosage of 5 mg PO every 12 hours. Monitor for sedation or respiratory depression.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as quetiapine. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures. If coadministration is considered necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
    Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include quetiapine.
    Paroxetine: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with drugs that are dopamine antagonists such as quetiapine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving quetiapine and an SSRI should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
    Pasireotide: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval, such as pasireotide as coadministration may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. If pazopanib and quetiapine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and quetiapine, a CYP3A4 substrate, may cause an increase in systemic concentrations of quetiapine. Use caution when concurrent administration is necessary.
    Pentamidine: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with quetiapine include pentamidine. Pentamidine has been associated with QT prolongation.
    Pentazocine: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
    Pentazocine; Naloxone: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
    Pentobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as quetiapine.
    Pergolide: (Moderate) Pergolide is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of pergolide. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior.
    Perphenazine: (Moderate) Avoid coadministration of perphenazine and quetiapine due to the potential for additive effects on the QT interval. Both quetiapine and perphenazine may be associated with QT prolongation. Concurrent use may increase this risk. Coadministration of perphenazine with atypical agents (e.g., quetiapine) may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Perphenazine; Amitriptyline: (Moderate) Avoid coadministration of perphenazine and quetiapine due to the potential for additive effects on the QT interval. Both quetiapine and perphenazine may be associated with QT prolongation. Concurrent use may increase this risk. Coadministration of perphenazine with atypical agents (e.g., quetiapine) may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Phenelzine: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Phenobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Phenylephrine; Promethazine: (Major) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Due to the risk of additive QT prolongation and potential for serious arrhythmias, avoid co-use with quetiapine if possible. In addition, co-administration of promethazine with antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from these combinations has not been established and data are very limited, the risk appears to be increased during combined use versus use of an antipsychotic alone.
    Phenytoin: (Major) Increased doses of quetiapine may be required for control of psychotic symptoms when phenytoin is administered concurrently. Coadministration of phenytoin (100 mg three times daily) and quetiapine (250 mg three times daily) increased the clearance of quetiapine by 5-fold. Chronic administration (7 to 14 days) of a potent CYP3A4 inducer, such as phenytoin, with quetiapine may require increases of the quetiapine dosage of up to 5-fold of the original dose. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Use quetiapine cautiously in patients with a history of seizures or with conditions that may lower the seizure threshold.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as quetiapine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Coadministration may increase the risk for QT prolongation.
    Pimozide: (Severe) Quetiapine has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Pirbuterol: (Minor) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Pitolisant: (Major) Avoid coadministration of pitolisant with quetiapine as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Posaconazole: (Severe) Concurrent use of posaconazole and quetiapine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quetiapine. These drugs used in combination may result in elevated quetiapine plasma concentrations, causing an increased risk for quetiapine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quetiapine.
    Pramipexole: (Moderate) Pramipexole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of pramipexole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior.
    Pramlintide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Prednisolone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Prednisone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include quetiapine.
    Primidone: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Procainamide: (Major) Quetiapine should be used cautiously and with close monitoring with procainamide. Procainamide is associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Prochlorperazine: (Moderate) Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation. According to the manufacturer, quetiapine should be avoided in combination with other drugs having an association with QT prolongation. In addition, co-administration of prochlorperazine with atypical agents (e.g., aripiprazole, lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent (see separate drug monographs). Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Promethazine: (Major) Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Due to the risk of additive QT prolongation and potential for serious arrhythmias, avoid co-use with quetiapine if possible. In addition, co-administration of promethazine with antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from these combinations has not been established and data are very limited, the risk appears to be increased during combined use versus use of an antipsychotic alone.
    Propafenone: (Major) Concurrent use of quetiapine and propafenone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Propafenone is a Class IC antiarrhythmic which also increases the QT interval, but largely due to prolongation of the QRS interval.
    Propantheline: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Propoxyphene: (Moderate) The central nervous system (CNS) effects of propoxyphene and other CNS depressants are additive. Concomitant use of propoxyphene with other CNS depressants can potentiate respiratory depression and/or sedation.
    Quazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Quinidine: (Major) Quetiapine should be used cautiously and with close monitoring with quinidine. Quinidine is associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Quinine: (Major) Concurrent use of quinine and quetiapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, concentrations of quetiapine may be increased with concomitant use of quinine. Quetiapine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
    Ranolazine: (Major) Ranolazine may increase plasma concentrations of quetiapine through CYP3A4 inhibition. Avoid co-use if possible, as both drugs have been noted to cause QTc interval prolongation. If co-use is necessary, use the combination with caution. The manufacturer of quetiapine recommends a reduced dosage of quetiapine during concurrent administration of CYP3A4 inhibitors.
    Rasagiline: (Minor) It is possible that dopamine antagonists, such as the atypical antipsychotics, could diminish the effectiveness of rasagiline. Additive CNS effects are also possible.
    Remifentanil: (Moderate) Concomitant use of remifentanil with other CNS depressants, including atypical antipsychotics, can potentiate the effects of remifentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ribociclib: (Major) Avoid coadministration of ribociclib with quetiapine due to an increased risk for QT prolongation. Systemic exposure of quetiapine may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Limited data, including some case reports, suggest that quetiapine, a sensitive CYP3A4 substrate, may also be associated with a significant prolongation of the QTc interval in rare instances. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with quetiapine due to an increased risk for QT prolongation. Systemic exposure of quetiapine may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Limited data, including some case reports, suggest that quetiapine, a sensitive CYP3A4 substrate, may also be associated with a significant prolongation of the QTc interval in rare instances. Concomitant use may increase the risk for QT prolongation.
    Rifabutin: (Moderate) Increased doses of quetiapine may be required to maintain symptom control if rifabutin is used concomitantly. Rifabutin is a less potent inducer of CYP3A4 than rifampin, a potent inducer. However, increased doses of quetiapine up to 5 fold may be required to maintain control of symptoms in patients receiving quetiapine and known potent CYP3A4 inducers. There are no specific recommendations for moderate inducers. When rifabutin is discontinued, the dose of quetiapine should be reduced to the original level within 7 to 14 days.
    Rifampin: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks.
    Rifapentine: (Moderate) Increased doses of quetiapine may be required to maintain symptom control if rifapentine is used concomitantly. rifapentine is a less potent inducer of CYP3A4 than rifampin, a potent inducer. However, increased doses of quetiapine up to 5-fold may be required to maintain control of symptoms in patients receiving quetiapine and known potent CYP3A4 inducers. There are no specific recommendations for moderate inducers. When rifapentine is discontinued, the dose of quetiapine should be reduced to the original level within 7 to 14 days.
    Rilpivirine: (Major) Concurrent use of quetiapine and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include quetiapine. Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Additionally, according to the manufacturer, no significant kinetic drug interactions were identified when quetiapine was coadministered with haloperidol or risperidone.
    Ritonavir: (Major) The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of strong CYP3A4 inhibitors, such as ritonavir. When ritonavir is discontinued, the dose should be increased by 6-fold. The plasma concentrations of quetiapine may be elevated when administered concurrently with ritonavir.
    Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. If romidepsin and quetiapine must be coadministered, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
    Ropinirole: (Moderate) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior.
    Rotigotine: (Moderate) Rotigotine is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of rotigotine. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior.
    Safinamide: (Minor) It is possible that dopamine antagonists, such as the atypical antipsychotics, could diminish the effectiveness of safinamide. Additive CNS effects may also be possible.
    Salmeterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Saquinavir: (Major) Avoid concurrent use of quetiapine and saquinavir due to the potential for additive effects on the QT interval and torsade de pointes. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Saquinavir may be associated with QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. Saquinavir may also inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of saquinavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. If saquinavir is discontinued, increase the quetiapine dose by 6-fold.
    Saxagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Scopolamine: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Secobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Selegiline: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Semaglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Sertraline: (Major) Avoid coadministration of quetiapine with sertraline due to the potential for additive QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. QTc prolongation and torsade de pointes (TdP) have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with quetiapine. Halogenated anesthetics can prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    SGLT2 Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Short-acting beta-agonists: (Minor) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Sibutramine: (Major) Caution and close monitoring should be observed when administering sibutramine with drugs that are dopamine antagonists such as the atypical antipsychotics. Monitor for CNS depression, changes in mood or behavior, and for other drug-related adverse reactions. Sibutramine has not been systematically evaluated in combination with antipsychotic medications. Sibutramine is a serotonin reuptake inhibitor that also inhibits norepinephrine and dopamine reuptake. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of quetiapine, which is a CYP3A4 substrate. Monitor patients for adverse effects of quetiapine, such as QT prolongation and GI effects.
    Simvastatin; Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Siponimod: (Major) Avoid coadministration of siponimod and quetiapine due to the potential for additive QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that are known to induce Antidiuretic Hormone Secretion (SIADH), such as antipsychotics, as these drugs may increase the risk of water retention and/or electrolyte imbalance.
    Solifenacin: (Major) Concurrent use of quetiapine and solifenacin should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP) and an increased risk of anticholinergic side effects. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. If concurrent use is required, also monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents, such as solifenacin. Constipation may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Sorafenib: (Major) Avoid coadministration of quetiapine with sorafenib due to the risk of QT prolongation. Sorafenib has been associated with QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Sotalol: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    Sparfloxacin: (Severe) Quetiapine may rarely be associated with significant prolongation of the QTc interval. Caution is advised when administering quetiapine with drugs having an established causal association with QT prolongation and torsade de pointes including sparfloxacin.
    St. John's Wort, Hypericum perforatum: (Major) Coadministration of St. John's Wort, a potent CYP3A4 inducer, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks.
    Sufentanil: (Moderate) Concomitant use of sufentanil with other CNS depressants, including atypical antipsychotics, can potentiate the effects of sufentanil on respiration, alertness, and blood pressure. A dose reduction of one or both drugs may be warranted.
    Sulfonylureas: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Sunitinib: (Major) According to the manufacturer, the use of quetiapine should be avoided in combination with drugs known to increase the QT interval such as sunitinib. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP).
    Tacrolimus: (Major) Concurrent use of quetiapine and tacrolimus should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Tacrolimus also causes QT prolongation. Additionally, both tacrolimus and quetiapine are substrates for CYP3A4. When coadministrating tacrolimus with other substrates of CYP3A4, it is recommended to reduce the tacrolimus dose and closely monitor tacrolimus whole blood concentrations.
    Tamoxifen: (Major) Avoid coadministration of tamoxifen with quetiapine due to an increased risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have been described when tamoxifen is used at lower doses. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Tapentadol: (Moderate) Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants. Severe hypotension, profound sedation, coma, or respiratory depression may occur. Prior to concurrent use of tapentadol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with tapentadol, a reduced dosage of tapentadol and/or the CNS depressant is recommended. If the extended-release tapentadol tablets are used concurrently with a CNS depressant, it is recommended to use an initial tapentadol dose of 50 mg PO every 12 hours. Monitor patients for sedation and respiratory depression.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering quetiapine with telaprevir due to an increased potential for quetiapine-related adverse events. If quetiapine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of quetiapine. Quetiapine is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated quetiapine plasma concentrations.
    Telavancin: (Major) Concurrent use of quetiapine and telavancin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Telavancin has been associated with QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Telithromycin: (Major) Concurrent use of quetiapine and telithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Both telithromycin and quetiapine are associated with a risk for QT prolongation. In addition, the cytochrome P450 3A4 (CYP3A4) isoenzyme is involved in the metabolism of quetiapine. It is recommended to reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events when used with a potent CYP inhibitor, such as telithromycin. If telithromycin is discontinued, increase the quetiapine dose by 6-fold.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and quetiapine is necessary, as the systemic exposure of quetiapine may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of quetiapine; consider increasing the dose of quetiapine if necessary. Quetiapine is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Temazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Terbutaline: (Minor) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as quetiapine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, concurrent use of quetiapine and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
    Tezacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and quetiapine concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as quetiapine, can increase quetiapine exposure leading to increased or prolonged therapeutic effects and adverse events.
    Thiazide diuretics: (Moderate) Caution is advisable during concurrent use of quetiapine and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
    Thiazolidinediones: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Thiethylperazine: (Major) Concurrent use of quetiapine with other antipsychotics, like phenothiazines, is not generally recommended. If used concomitantly with quetiapine, other antipsychotics may increase the risk of adverse effects such as drowsiness, sedation, dizziness, or orthostatic hypotension.
    Thiopental: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
    Thioridazine: (Severe) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval, such as quetiapine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with a phenothiazine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Further, thioridazine increases the oral clearance of quetiapine by about 65%.
    Thiothixene: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use may be associated with adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of thiothixene and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Tiotropium; Olodaterol: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Tipranavir: (Major) Avoid concurrent use of quetiapine and tipranavir. Tipranavir boosted with ritonavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of tipranavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If tipranavir is discontinued, increase the quetiapine dose by 6-fold.
    Tolcapone: (Moderate) Dopamine-receptor antagonists, including the atypical antipsychotics, may reduce the effects of the COMT inhibitors (e.g., entacapone, tolcapone). In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. Monitor for diminished effectiveness of the antiparkinson treatments, for movement disorders, and for unusual changes in moods or behavior.
    Tolterodine: (Major) Concurrent use of quetiapine and tolterodine should be avoided if possible due to an increased risk for QT prolongation, torsade de pointes (TdP), and anticholinergic effects. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. If concurrent use is required, also monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents, such as tolterodine. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro binding affinity for several muscarinic receptor subtypes.
    Toremifene: (Major) Avoid coadministration of quetiapine with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances.
    Tramadol: (Moderate) Due to the primary CNS effects of quetiapine, caution should be used when given in combination with other centrally acting medications, such as tramadol. Both of these medications can lower the seizure threshold when used alone, therefore there is an even greater risk when they are used concomitantly.
    Trandolapril; Verapamil: (Minor) Verapamil may inhibit the CYP3A4-mediated metabolism of quetiapine, leading to increased serum concentrations of quetiapine. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
    Tranylcypromine: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Trazodone: (Major) Avoid coadministration of trazodone and quetiapine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of TdP. Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
    Triamcinolone: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Triazolam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
    Tricyclic antidepressants: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Trifluoperazine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. According to the manufacturer, quetiapine should not be used with other drugs having an association with QT prolongation. Co-administration of trifluoperazine with atypical agents (e.g., lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Trihexyphenidyl: (Moderate) When administering systemic anticholinergics and quetiapine together, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
    Triprolidine: (Moderate) Co-administration of quetiapine with sedating H1-blockers such as triprolidine may result in additive CNS effects including somnolence and drowsiness.