PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Antidepressant Augmentation Drugs
    Partial Dopamine Receptor Agonist Antipsychotics

    BOXED WARNING

    Children, suicidal ideation

    Aripiprazole has been used and FDA-approved in pediatric patients 6 years of age or older for selected indications. Injectable formulations of aripiprazole are not approved for any indication in pediatric patients. A causal role has been demonstrated with antidepressant use and emergence of suicidality in pediatric patients and young adults in a pooled evaluation of clinical studies, including 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 or adjunct to antidepressant therapy 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. It is unknown if the suicidality risk in children, adolescents, and young adults extends to longer-term therapy (i.e., beyond several months). It is advisable to closely observe all aripiprazole-treated patients, regardless of age, with major depressive disorder (MDD) or comorbid depression for clinical worsening and suicidal ideation, 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. In patients who exhibit changes in symptoms, worsening of depression, or suicidality, discontinuation of treatment may be necessary. If discontinuing, the medication should be tapered as rapidly as possible, but with recognition that discontinuing treatment abruptly may cause adverse symptoms. Prescriptions for aripiprazole should be written for the smallest quantity possible to reduce the risk of overdose.

    Dementia, geriatric, stroke

    Placebo-controlled studies of immediate-release dosage forms of aripiprazole in patients with schizophrenia, bipolar mania, or major depressive disorder did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience and pharmacokinetic data have not identified differences in responses between the elderly and younger adult patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Antipsychotics are not approved for the treatment of dementia-related psychosis in elderly patients. In April 2005 the FDA mandated that all manufacturers of atypical antipsychotics include a boxed warning to the labeling indicating that increased death rates (1.6 to 1.7 times that of placebo) have been noted in this patient population receiving atypical antipsychotics. Death typically occurred due to heart failure, sudden death, or infections (primarily pneumonia). Of 17 placebo controlled trials (n = 5,106) performed with olanzapine, aripiprazole, risperidone, or quetiapine in elderly patients with dementia-related psychosis, 15 showed numerical increases in mortality in the active compared to the placebo-treated patients. In aripiprazole placebo-controlled trials of dementia-related psychosis, there was an increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in aripiprazole-treated patients (mean age 84 years; range 78 to 88 years). In 1 study, there was a statistically significant dose response relationship for cerebrovascular adverse events in patients treated with aripiprazole. In a 10-week placebo-controlled study of aripiprazole in elderly patients with psychosis associated with Alzheimer's dementia, 3.8% (4 of 105 patients) of aripiprazole-treated patients died compared to no deaths in placebo treated patients during, or within 30 days after, termination of the double-blind portion of the study. Three of the patients died following discontinuation of aripiprazole with reported cause of death due to pneumonia, heart failure, or shock and the fourth patient died following hip surgery while in the double-blind phase of the study. 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. In addition, avoidance of aripiprazole is recommended in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: delirium (possible new-onset or worsening delirium) and dementia (adverse CNS effects). There is an increased risk of stroke and greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics, and 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. The Panel recommends avoiding 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 additional falls; if an antipsychotic must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. 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, aripiprazole appears less likely to precipitate a worsening of symptoms than most other antipsychotics and is excluded from the recommendation. Because antipsychotics can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. 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 that meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. There is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. Therefore, identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic. To initiate antipsychotic therapy, behavioral symptoms must be a danger to self or others and are either 1) due to mania or psychosis or 2) the plan of care includes documentation of attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less with evaluation and documentation within 7 days which identifies and addresses contributors/causes. For acute conditions persisting beyond 7 days, pertinent 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 include monitoring that ensures the behavioral symptoms are not due to a treatable or correctable medical condition, are not due to correctable environmental or treatable psychological stressors alone, and provides clearly documented evidence of persistence. The LTCF must evaluate the appropriateness of the antipsychotic during or within 2 weeks of admission for a newly admitted resident on an antipsychotic. In all cases, the lowest possible dose and shortest duration should be prescribed. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Monitoring of antipsychotics should include evaluation of ongoing effectiveness, rationale for use, and potential adverse effects (e.g., anticholinergic effects, neurological symptoms, metabolic syndrome, cardiac effects). Antipsychotics are subject to periodic review for effectiveness, necessity, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    DEA CLASS

    Rx

    DESCRIPTION

    Atypical antipsychotic of dopamine system stabilizers subclass
    Used orally as an adjunct for depression in adults, for bipolar I disorder (monotherapy or as an adjunct to lithium or valproate) in adults and pediatrics, for schizophrenia in adults and adolescents, and in pediatric patients the drug is additionally approved for irritability with autistic disorder, and for Tourette's disorder
    Short-acting injection used for agitation from schizophrenia or bipolar disorder in adults
    Two different long-acting IM injections are available for the maintenance treatment of schizophrenia in adults
    As with all antipsychotics, boxed warning for increased mortality risk in elderly patients with dementia-related psychosis

    COMMON BRAND NAMES

    Abilify, Abilify Discmelt, Abilify Maintena, Aristada

    HOW SUPPLIED

    Abilify Discmelt/Aripiprazole Oral Tab Orally Dis: 10mg, 15mg
    Abilify Maintena Intramuscular Inj Pwd F/Susp ER: 300mg, 400mg
    Abilify/Aripiprazole Oral Sol: 1mg, 1mL
    Abilify/Aripiprazole Oral Tab: 2mg, 5mg, 10mg, 15mg, 20mg, 30mg
    Aristada Intramuscular Inj Susp: 1.6mL, 2.4mL, 3.2mL, 441mg, 662mg, 882mg

    DOSAGE & INDICATIONS

    For the treatment of schizophrenia.
    For use as monotherapy.
    Oral dosage
    Adults

    10 mg or 15 mg PO once daily. Effective dosage range: 10 mg/day to 30 mg/day. However dosages greater than 10 mg to 15 mg/day PO were not more effective than the initial doses in clinical trials. Titrate no more frequently than every 2 weeks, the time needed to achieve steady state. Max: 30 mg/day PO. ORAL SOLUTION DOSING: The oral solution of aripiprazole can be substituted for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose). SWITCHING FROM OTHER ANTIPSYCHOTICS: In 1 study, the following regimens were safe and effective: 1) initiation with simultaneous discontinuation of the current antipsychotic monotherapy; 2) immediate initiation with a 2-week taper of the current antipsychotic; or 3) a 2-week up-titration of aripiprazole while simultaneously tapering the current antipsychotic. Adverse events were comparable across treatment groups and time-limited. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients, more gradual discontinuation may be most appropriate.

    Adolescents

    Initially, 2 mg PO once daily. After 2 days increase to 5 mg PO once daily, and after 2 more days increase to the target dose of 10 mg PO once daily. Then, titrate in 5 mg increments, usually every 2 weeks to allow assessment of effectiveness and tolerability. Up to 30 mg/day has been studied; however, this dose does not appear to be more effective than the 10 mg/day dose. Max: 30 mg/day PO. ORAL SOLUTION DOSING: The oral solution of aripiprazole can be substituted for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

    Intramuscular dosage (monthly extended-release injectable suspension; i.e., Abilify Maintena)
    Adults

    Initially, Abilify Maintena 400 mg IM once monthly, with maintenance dose administered no sooner than 26 days after the previous injection. At initiation, oral aripiprazole (10 mg to 20 mg per day) or other oral antipsychotic should be continued for 14 consecutive days to maintain therapeutic concentrations during initiation of IM aripiprazole therapy. Clinical trials have shown efficacy of the extended-release injection for both maintenance treatment of schizophrenia and in treating acutely relapsed adult patients. Once stabilized, may reduce to 300 mg IM once monthly based upon tolerability. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose). MISSED DOSES: 1) If the second or third dose is missed and more than 4 weeks but less than 5 weeks have elapsed since the last injection: Administer the injection as soon as possible. 2) If the second or third dose is missed and more than 5 weeks have elapsed since the last injection: Restart concomitant oral aripiprazole for 14 days with the next administered injection. 3) If the fourth or subsequent dose is missed and greater than 4 weeks but less than 6 weeks have elapsed since the last injection: Administer the injection as soon as possible. 4) If the fourth or subsequent dose is missed and more than 6 weeks have elapsed since the last injection: restart concomitant oral aripiprazole for 14 days with the next administered injection.

    Intramuscular dosage (extended-release aripiprazole lauroxil injectable suspension; i.e., Aristada)
    Adults and Geriatric Adults up to 65 years

    INITIAL DOSE: Establish tolerability with oral aripiprazole prior to initiating treatment in those patients who have never received aripiprazole. Due to the long half-life of aripiprazole, it may take up to 2 weeks to fully evaluate tolerability. Initiate Aristada at 441 mg, 662 mg, or 882 mg IM monthly, or 882 mg IM every 6 weeks. The dose and dosing interval may be adjusted as needed, taking into account the pharmacokinetics and prolonged-release characteristics of Aristada. CONVERSION FROM ORAL DOSING: In conjunction with the first dose of Aristada, administer oral aripiprazole for 21 days as follows: 10 mg/day PO along with 441 mg/month IM, 15 mg/day PO along with 662 mg/month IM, and 20 mg/day or higher PO along with 882 mg/month IM. CONVERSION FROM ABILIFY MAINTENA EXTENDED-RELEASE IM INJECTION: Abilify Maintena doses of 300 mg, 450 mg, or 600 mg IM monthly correspond to 441 mg, 662 mg, or 882 mg IM monthly, respectively, of Aristada. The 441 mg dose may be administered in the deltoid or gluteal muscle, whereas all other doses and dosing regimens (662 mg monthly, 882 mg monthly, or 882 mg every 6 weeks) should be administered in the gluteal muscle. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose). EARLY DOSING: If early dosing is needed, the injection should not be given earlier than 14 days after the previous injection. MISSED DOSES: 1) For patients who miss a dose while receiving 441 mg/month IM: If it has been 6 weeks or less since the missed dose, no oral supplementation is required. If it has been more than 6 weeks but not more than 7 weeks since the missed dose, supplement with 7 days of oral aripiprazole at the same dose of oral aripiprazole as when the patient began Aristada. If it has been more than 7 weeks since the missed dose, supplement with 21 days of oral aripiprazole at the same dose of oral aripiprazole as when the patient began Aristada. 2) For patients who miss a dose while receiving 662 mg/month, 882 mg/month, or 882 mg every 6 weeks IM: If it has been 8 weeks or less since the missed dose, no oral supplementation is required. If it has been more than 8 weeks but not more than 12 weeks since the missed dose, supplement with 7 days of oral aripiprazole at the same dose of oral aripiprazole as when the patient began Aristada. If it has been more than 12 weeks since the missed dose, supplement with 21 days of oral aripiprazole at the same dose of oral aripiprazole as when the patient began Aristada.

    For the acute treatment of mania and mixed episodes and maintenance treatment of bipolar disorder (Bipolar I Disorder).
    For monotherapy of bipolar I disorder.
    Oral dosage
    Adults

    Initially, 15 mg/day PO. Based upon response and tolerability, may increase if clinically indicated. Max: 30 mg/day PO. If maintenance treatment is clinically indicated, use the same dose needed to stabilize the patient during acute treatment. Use the lowest effective dosage. Periodically reassess to evaluate the need for continued maintenance therapy. Maintenance studies included adults who had been stabilized on aripiprazole for at least 6 weeks; the delay in relapse (both time to relapse and total number of relapses) was significant for the manic, but not the depressive phase. ORAL SOLUTION DOSING: The oral solution can be substituted for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

    Children and Adolescents 10 years and older

    Initially, 2 mg PO once daily. Titrate to 5 mg PO once daily after 2 days, and then titrate to a target dose of 10 mg/day PO after an additional 2 days. Subsequent increases should occur in increments of 5 mg/day. Max: 30 mg/day PO. Use the lowest effective dosage. Periodically reassess the need for continued maintenance therapy. ORAL SOLUTION DOSING: The oral solution can be substituted for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

    For the treatment of bipolar disorder as adjunctive therapy to lithium or valproate.
    Oral dosage
    Adults

    Initially, 10 mg to 15 mg PO once daily. May titrate based on clinical response and tolerance. Max: 30 mg/day PO. If maintenance treatment is clinically indicated, use the same dose needed to stabilize the patient during acute treatment and determine the lowest effective dosage. Periodically reassess the need for continued treatment. Maintenance studies included adults who had been stabilized on aripiprazole for at least 6 weeks; the delay in relapse (both time to relapse and total number of relapses) was significant for the manic, but not the depressive phase. ORAL SOLUTION DOSING: The oral solution can be substituted for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

    Children and Adolescents 10 years and older

    Initially, 2 mg PO once daily. Titrate to 5 mg PO once daily after 2 days, and then titrate to a target dose of 10 mg/day PO after an additional 2 days. Subsequent increases should occur in increments of 5 mg/day. Max: 30 mg/day PO. Determine the lowest effective dosage. Periodically reassess the need for continued maintenance therapy. ORAL SOLUTION DOSING: The oral solution can be substituted for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

    For the treatment of agitation associated with schizophrenia or bipolar mania.
    Intramuscular dosage (injection solution)
    Adults

    9.75 mg IM as a single dose. A lower dosage of 5.25 mg IM may be used if clinically warranted such as patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs). Subsequent administration may be considered if necessary; however, the efficacy of repeated dosages and the safety of administration more frequently than every 2 hours have not been established in controlled clinical trials. Maximum cumulative dose: 30 mg/day IM. Total daily doses greater than 30 mg have not been adequately studied. Single doses of 15 mg were not found superior to 9.75 mg in clinical trials. Patients requiring long-term treatment with aripiprazole should be changed to oral administration of the drug as soon as possible.

    For the adjunctive treatment of major depression.
    Oral dosage
    Adults

    Initially, 2 mg PO once daily to 5 mg PO once daily as an adjunct to previously established antidepressant treatment. Adjust dose in increments of up to 5 mg at intervals of no less than 1 week each. The effective dose range is 2 mg/day to 15 mg/day PO. Periodically reassess to determine the need for continued treatment. NOTE: No dosage adjustments are needed in patients with major depressive disorder receiving adjunct aripiprazole within this dose range with concomitant CYP modulators or for patients who are CYP2D6 poor metabolizers.

    For the short-term treatment of irritability associated with autistic disorder.
    Oral dosage
    Children and Adolescents 6 years and older

    Initially, 2 mg PO once daily. Increase dose to 5 mg PO once daily after 1 week. Further titration should occur in increments of 5 mg/day at intervals of no less than 1 week. Recommended dose range: 5 mg to 10 mg PO once daily. Individualize regimen based upon response and tolerability. Max: 15 mg/day PO. Periodically reassess to determine the need for continued treatment. Short-term efficacy was established in 2 placebo-controlled trials (8 week duration). In a maintenance trial, patients were initially stabilized with aripiprazole (2 mg/day to 15 mg/day) for 12 weeks (stabilization defined as greater than 25% improvement on the ABC-I subscale, and a CGI-I rating of much improved or very much improved). In the second phase of the maintenance trial (stabilized patients randomized to receive aripiprazole or placebo for an additional 16 weeks, n = 85), long-term efficacy was not established. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers ( CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

    For the treatment of Tourette's syndrome.
    Oral dosage
    Children and Adolescents 6 years and older

    WEIGHING AT LEAST 50 KG: Initially, 2 mg PO once daily. After 2 days, increase to 5 mg PO once daily, and then after 5 more days increase to the target dose of 10 mg PO once daily. Increase gradually by 5 mg/day increments at weekly intervals as needed to achieve optimal control of tics. Max: 20 mg/day PO. Periodically reassess the need for continued maintenance treatment. WEIGHING LESS THAN 50 KG: Initially, 2 mg PO once daily. After 2 days, increase dose to 5 mg PO once daily. Increase gradually at weekly intervals as needed to achieve optimal control of tics. Max: 10 mg/day PO. Periodically reassess the need for continued maintenance treatment. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary during treatment with aripiprazole; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

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

    Initially, 2 mg or 5 mg PO once daily, with gradual titration of the daily dose according to response and tolerance, usually by no more than 5 mg/day every week. Maximum suggested dose: 10 mg/day PO. A 2011 off-label use of review by the Agency for Healthcare Research and Quality (AHRQ) stated aripiprazole is efficacious for behavioral symptoms of dementia and for agitation. Antipsychotics are not FDA-approved for this indication 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: 10 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. ORAL SOLUTION DOSING: The oral solution can be substituted for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are also receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    30 mg/day PO tablets and 25 mg/day PO oral solution; 30 mg/day immediate-release IM; 400 mg/month extended-release IM (Abilify Maintena); 882 mg/month extended-release IM (Aristada).

    Geriatric

    30 mg/day PO tablets and 25 mg/day PO oral solution; 30 mg/day immediate-release IM; 400 mg/month extended-release IM (Abilify Maintena); 882 mg/month extended-release IM (Aristada) but safety and efficacy of Aristada not established in geriatric adults over 65 years of age.

    Adolescents

    Weight greater than or equal to 50 kg: 30 mg/day PO for schizophrenia and bipolar disorder; 15 mg/day PO for autism; 20 mg/day PO for Tourette's syndrome; safety and efficacy of the immediate-release (Abilify) and extended-release IM injections (Abilify Maintena, Aristada) have not been established.
    Weight less than 50 kg: 30 mg/day PO for schizophrenia and bipolar disorder; 15 mg/day PO for autism; 10 mg/day PO for Tourette's syndrome; safety and efficacy of the immediate-release (Abilify) and extended-release IM injections (Abilify Maintena, Aristada) have not been established.

    Children

    Greater than or equal to 10 years and weighing greater than or equal to 50 kg: 30 mg/day PO for bipolar disorder; 15 mg/day PO for autism; 20 mg/day PO for Tourette's syndrome; not indicated for schizophrenia.
    Greater than or equal to 10 years and weighing less than 50 kg: 30 mg/day PO for bipolar disorder; 15 mg/day PO for autism; 10 mg/day PO for Tourette's syndrome; not indicated for schizophrenia.
    6—9 years weighing greater than or equal to 50 kg: 15 mg/day PO for autism; 20 mg/day PO for Tourette's syndrome; not indicated for bipolar disorder or schizophrenia.
    6—9 years weighing less than 50 kg: 15 mg/day PO for autism; 10 mg/day PO for Tourette's syndrome; not indicated for bipolar disorder or schizophrenia.
    Under 6 years: Safe and effective use has not been established.

    Infants

    Not indicated.

    Neonates

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are necessary.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are necessary.
     
    Intermittent hemodialysis
    Hemodialysis is unlikely to be effective in removing aripiprazole since the drug is highly bound to plasma proteins.

    ADMINISTRATION

    Oral Administration

    May be administered without regard to meals.

    Oral Solid Formulations

    Orally disintegrating tablets (e.g., Abilify DiscMelt): Do not open the blister until ready to administer. Do not push the tablet through the foil because this could damage the tablet. Tablet disintegration occurs rapidly in saliva. Place the tablet on the tongue and allow to dissolve. Do not take with liquid unless it is necessary to do so. Do not divide the tablets in half.

    Oral Liquid Formulations

    Oral solution: Administer using a calibrated measuring device.
    Storage: Opened bottles of aripiprazole oral solution can be used for up to 6 months after opening, but not beyond the expiration date on the bottle.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intramuscular Administration

    Immediate-release intramuscular injection solution (i.e. Abilify short-acting injection):
    For intramuscular use only. Do NOT administer intravenously or subcutaneously.
    Available as a ready-to-use injectable solution.
    Inject slowly and deeply into muscle mass.
    Discard any unused portion.
     
    Extended-release intramuscular injection (i.e., Abilify Maintena) Single-Use Vial Preparation, Reconstitution, and Administration:
         Preparation of adapter-syringe assembly:
    Use appropriate aseptic technique.
    Remove cover from vial adapter package. Do not remove vial adapter from package. Using vial adapter package to handle the vial adapter, attach the prepackaged luer lock syringe to the vial adapter.
    Use the luer lock syringe to remove the vial adapter from the package and discard the vial adapter package. Do not touch the spike tip of the adapter at any time.
         Reconstitution of single-use vial for suspension:
    Use appropriate aseptic technique and reconstitute at room temperature.
    The lyophilized powder should be suspended with the 5 mL vial of Sterile Water for Injection supplied in the kit.
    For the 400 mg vial, reconstitute with 1.9 mL of Sterile Water for Injection. For a 300 mg vial, reconstitute with 1.5 mL of Sterile Water for Injection.
    Using the syringe with pre-attached hypodermic safety needle, withdraw pre-determined Sterile Water volume into the syringe.
    Discard residual water that remains in the 5 mL vial of Sterile Water for Injection after reconstitution.
    After slowly injecting the Sterile Water for Injection into the vial of lyophilized powder, withdraw air equal to pressure in the vial. Remove needle from the vial.
    Engage the needle safety device using a one-handed technique. Gently press the sheath against a flat surface until the needle is firmly engaged in the needle protection sheath. Visually confirm that the needle is fully engaged into the needle protection sheath, and discard.
     
          Dose Preparation from the single-use vial:
    Shake the reconstituted vial vigorously for 30 seconds. The reconstituted suspension should be uniform, homogenous, opaque, and milky white in color.
    Determine the recommended volume for injection.
    Using the 400 mg reconstituted vial: 400 mg = 2 mL, 300 mg = 1.5 mL, 200 mg = 1 mL, 160 mg = 0.8 mL.
    Using the 300 mg reconstituted vial: 300 mg = 1.5 mL, 200 mg = 1 mL, 160 mg = 0.8 mL.
    Wipe top of the reconstituted vial with a sterile alcohol swab. Place and hold the reconstituted vial on a hard surface. 
    Attach the adapter-syringe assembly to vial by holding the outside of the adapter and pushing adapter's spike firmly through the rubber stopper until the adapter snaps in place.
    Slowly withdraw recommended volume into the luer lock syringe. NOTE: A small amount of excess product will remain in the vial.
    Detach the luer lock syringe containing the suspension from the vial. Attach syringe to the appropriate needle.
    For deltoid administration, use the 23 gauge, 1-inch needle in non-obese patients and the 22 gauge, 1.5-inch needle in obese patients.
    For gluteal administration, use the 22 gauge, 1.5-inch needle in non-obese patients and the 21 gauge, 2-inch needle in obese patients.
    Ensure needle is firmly seated on safety device with a push and clockwise twist; pull the needle cap straight from the needle.
     
          Dose Administration and Disposal:
    For once-monthly deep intramuscular gluteal or deltoid injection by a healthcare professional only. Do NOT administer by any other route.
    For single-use only. Discard any unused portion.
    Use immediately after reconstitution and preparation of the syringe.
    Slowly inject the recommended volume as a single deep IM injection into the gluteal or deltoid muscle.
    Do not massage the injection site.
    After the injection, engage the needle safety device using a one-handed technique. Gently press the sheath against a flat surface until the needle is firmly engaged in the needle protection sheath. Appropriately dispose of the vials, adapter, needles, and syringe.
    Do not re-use any components of the kit.
    For subsequent injections, rotate sites of injection between the two gluteal or deltoid muscles.
    If not injected immediately, keep vial at room temperature and shake vigorously for at least 60 seconds to re-suspend before preparing the syringe for injection. Do not store suspension in a syringe.
     
     
    Extended-release intramuscular injection (i.e., Abilify Maintena) Pre-Filled Dual Chamber Syringe Preparation, Reconstitution, Administration, and Disposal:
    For once-monthly deep intramuscular gluteal or deltoid injection by a healthcare professional only. Do NOT administer by any other route.
    For single-use only. Discard any unused portion.
    Use immediately after reconstitution and preparation of the pre-filled syringe.
    Use appropriate aseptic technique and reconstitute at room temperature.
    Push plunger rod slightly to engage threads. Then, rotate plunger rod until the rod stops rotating to release diluent.
    After plunger rod is at complete stop, middle stopper will be at the indicator line.
    Vertically shake the syringe vigorously for 20 seconds until the drug is uniformly milky-white.The reconstituted suspension should be opaque and milky white in color.
    To inject, twist and pull off Over-cap and Tip-cap. Select the appropriate needle.
    For deltoid administration, use the 23 gauge, 1-inch needle in non-obese patients and the 22 gauge, 1.5-inch needle in obese patients.
    For gluteal administration, use the 22 gauge, 1.5-inch needle in non-obese patients and the 21 gauge, 2-inch needle in obese patients.
    While holding needle cap, ensure the needle is firmly seated on the safety device with a push; twist clockwise until snugly fitted. Pull needle-cap straight up.
    Hold syringe upright and advance plunger rod slowly to expel the air until the suspension fills the needle base. If it's not possible to advance the plunger rod to expel the air, check that the plunger rod is rotated to a complete stop.
    Slowly inject as a single deep IM injection into the gluteal or deltoid muscle.
    Do not massage the injection site.
    After the injection, engage the needle safety device and safely discard all kit components.
    For subsequent injections, rotate sites of injection between the two gluteal or deltoid muscles.
     
     
    Extended-release aripiprazole lauroxil intramuscular injection (i.e., Aristada) General Administration Guidelines:
    For administration as a long-acting intramuscular injection by a healthcare professional. Do NOT administer by any other route.
    Prior to being administered Aristada, the patient who has never received any form of aripiprazole will have had established tolerability with oral aripiprazole. In conjunction with the first Aristada injection, the patient will be administered treatment with oral aripiprazole for 21 consecutive days.
    The 441 mg dose may be administered in the deltoid or gluteal muscle, whereas all other doses (662 mg 882 mg) should be administered in the gluteal muscle.
    The dose and dosing interval may be adjusted, taking into account the pharmacokinetics and prolonged-release characteristics of Aristada.
    The usual dosage interval for administration, as ordered by the prescriber, should be maintained whenever possible. e.g., 441 mg once monthly, 662 mg once monthly, 882 mg once monthly, or 882 mg every 6 weeks. If early dosing is needed, the injection should not be given any earlier than 14 days after the previous injection. If the patient misses their usual scheduled dose, refer to the dosing and administration recommendations for patients which are determined by the length of time since last injection.
     
       Extended-release aripiprazole lauroxil intramuscular injection (i.e., Aristada) Single-Use, pre-filled Syringe Preparation, Administration, and Disposal:
    The kit contains a pre-filled syringe with Aristada sterile aqueous suspension and 2 or 3 safety needles depending upon the dose.
    Tap the syringe at least 10 times to dislodge any material which may have settled and shake vigorously for at least 30 seconds to ensure uniform suspension.
    If the syringe is not used within 15 minutes, shake again for 30 seconds.
    Select the injection needle based on injection site and dosage, as follows. For patients with a larger amount of subcutaneous tissue overlaying the injection site muscle, use the longer of the needles provided.
    441 mg dose: deltoid (21 gauge, 1-inch or 20 gauge, 1 1/2-inch), or gluteal (20 gauge, 1 1/2-inch or 20 gauge, 2-inch).
    662 mg dose: gluteal (20 gauge, 1 1/2-inch or 20 gauge, 2-inch).
    882 mg dose: gluteal (20 gauge, 1 1/2-inch or 20 gauge, 2-inch).
    Attach the injection needle to the syringe securely with a clockwise twisting motion. Do NOT overtighten, since this may lead to needle hub cracking.
    Prime the syringe to remove air.
    Bring the syringe into an upright position and tap the syringe to bring air to the top. Remove air by depressing the plunger rod. A few drops of suspension will be released.
    Administer the entire content intramuscularly. Do not inject by any other route. Inject in a rapid and continuous manner (less than 10 seconds).
    Cover the needle by pressing the safety device, and dispose of used and unused items in an appropriate waste container.

    STORAGE

    Abilify:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Abilify Discmelt:
    - Product should always be stored in the blister and only removed immediately before use
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Abilify Maintena:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Aristada:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Some reports suggest that a false positive urine drug screen may occur for amphetamines in patients who have ingested aripiprazole. Caution should be exercised when interpreting positive urine drug screens, and confirmation by alternative tests such as gas chromatography/mass spectrometry should be considered.

    Bipolar disorder, mania

    All effective antidepressants can transform depression into mania or hypomania in predisposed individuals. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. If a patient develops manic symptoms, aripiprazole should be withheld and appropriate therapy initiated to treat the manic symptoms. Additionally, depression may be the presenting symptom of a mixed/manic episode of bipolar disorder. Patients with depression or comorbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes. Caregivers should be advised to closely observe the patient on a daily basis and to communicate immediately with the prescriber the emergence of agitation, irritability, unusual changes in moods or behavior, or suicidality.

    Agranulocytosis, hematological disease, leukopenia, neutropenia

    Aripiprazole should be used with caution in patients with hematological disease. Hematologic effects including leukopenia, neutropenia, and agranulocytosis have been associated with antipsychotic use. 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 medication. 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 the antipsychotic 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. Aripiprazole should be discontinued in patients with severe neutropenia (ANC < 1000/mm3); ongoing medical care is recommended until the symptoms resolve.

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

    Aripiprazole can cause orthostatic hypotension associated with dizziness and, in rare cases, syncope; therefore, caution is advisable in patients with cardiac disease, cerebrovascular disease, pre-existing hypotension, or conditions that may predispose patients to hypotension (e.g., hypovolemia, dehydrated state, antihypertensive therapy). Orthostatic hypotension from antipsychotic use 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. In rare instances, QT prolongation has been reported during therapeutic use of aripiprazole and following overdose. Some drugs that prolong the QT interval have been associated with torsade de pointes (TdP), a life-threatening arrhythmia. Aripiprazole is considered a drug with a possible risk of TdP. Use aripiprazole 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. It is advisable to correct electrolyte imbalances prior to initiation of aripiprazole. Because QT prolongation can occur following an overdose, an electrocardiogram should be obtained in cases of overdose.

    Cerebrovascular disease, seizure disorder, seizures

    In clinical trials with aripiprazole, seizures occurred in a small number of adult (0.1%) and pediatric (0.3%) patients. In addition, seizures occurred in 0.2% and 0% of patients receiving intramuscular aripiprazole and placebo, respectively, during clinical trials. For this reason, aripiprazole should be used with caution in patients with a seizure disorder or with conditions that may lower the seizure threshold (e.g. cerebrovascular disease). Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.

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

    Somnolence (including sedation/drowsiness) was a commonly reported adverse effect in clinical trials (11% of patients on oral aripiprazole, 8% of patients on placebo). Somnolence was also reported in 9% of patients receiving intramuscular aripiprazole versus 6% of those receiving placebo during clinical trials. In addition, somnolence has been reported more frequently in pediatric patients receiving oral aripiprazole (21%) than placebo (5%) during clinical trials. Somnolence from antipsychotic use 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. Because aripiprazole may have the potential to impair judgment, thinking, or motor skills, patients should be cautioned about driving or operating machinery or other hazardous tasks until they are reasonably certain that aripiprazole therapy does not affect them adversely. Given the primary CNS effects of aripiprazole, caution should be used during coadministration with other CNS depressants and alcohol. Ethanol ingestion may further impair cognitive and motor skills and patients should generally be advised to avoid use of alcoholic beverages.

    Dysphagia

    Patients with dysphagia or who are at risk for aspiration pneumonia should be closely monitored while receiving aripiprazole. 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.

    Children, suicidal ideation

    Aripiprazole has been used and FDA-approved in pediatric patients 6 years of age or older for selected indications. Injectable formulations of aripiprazole are not approved for any indication in pediatric patients. A causal role has been demonstrated with antidepressant use and emergence of suicidality in pediatric patients and young adults in a pooled evaluation of clinical studies, including 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 or adjunct to antidepressant therapy 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. It is unknown if the suicidality risk in children, adolescents, and young adults extends to longer-term therapy (i.e., beyond several months). It is advisable to closely observe all aripiprazole-treated patients, regardless of age, with major depressive disorder (MDD) or comorbid depression for clinical worsening and suicidal ideation, 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. In patients who exhibit changes in symptoms, worsening of depression, or suicidality, discontinuation of treatment may be necessary. If discontinuing, the medication should be tapered as rapidly as possible, but with recognition that discontinuing treatment abruptly may cause adverse symptoms. Prescriptions for aripiprazole should be written for the smallest quantity possible to reduce the risk of overdose.

    Impulse control symptoms

    Postmarketing reports suggest that patients can experience intense compulsive urges, particularly for gambling, and the inability to control these urges while taking aripiprazole. Less frequently reported impulse control symptoms include eating or binge-eating, shopping, and sexual actions. In some cases, these uncontrollable urges stop when the medicine is discontinued or the dose is reduced. Healthcare providers should inform patients and caregivers of the risk of impulse control symptoms when prescribing aripiprazole. Because patients may not recognize these behavioral changes as abnormal, healthcare providers should specifically ask patients about any new or increasing urges or compulsions while they are being treated with aripiprazole. Healthcare providers should closely monitor for new or worsening uncontrollable urges in patients at higher risk for impulse-control problems (e.g., personal or family history of obsessive-compulsive disorder, impulse control disorder, bipolar disorder, impulsive personality, alcoholism, drug abuse, or other addictive behaviors). It should be noted that impulse control symptoms can also be associated with the underlying disorder. A reduction in dose or discontinuation of the medicine should be considered if such urges develop since they may result in harm to the patient or others.

    Diabetes mellitus, hyperglycemia

    Aripiprazole, like other atypical antipsychotic agents, may cause metabolic changes. Increased blood sugar or diabetes, dyslipidemia, and weight gain may occur during therapy. While all of the drugs in the atypical antipsychotic class have been shown to produce some metabolic changes, each drug has its own specific risk profile. Metabolic changes may increase cardiovascular or cerebrovascular risk over time. Metabolic changes are of particular concern patients with pre-existing risk factors, such as diabetes mellitus. Hyperglycemia, sometimes associated with diabetic ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. All patients treated with atypical antipsychotics, including aripiprazole, should be monitored for symptoms of hyperglycemia (e.g., polydipsia, polyuria, polyphagia, weakness). Patients with established diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obese patients, family history of diabetes) should undergo fasting blood glucose testing at the beginning of treatment. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the antipsychotic was discontinued; however, some patients required continuation of antidiabetic agents despite discontinuation of the suspect drug. Patients with diabetes should be advised that each mL of aripiprazole oral solution contains 400 mg of sucrose and 200 mg of fructose.

    Hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, obesity

    Aripiprazole, like other atypical antipsychotic agents, may cause metabolic changes. Increased blood sugar, dyslipidemia (increased cholesterol and/or triglycerides), and weight gain may occur during therapy. While all of the drugs in the atypical antipsychotic class have been shown to produce some metabolic changes, each drug has its own specific risk profile. Metabolic changes may increase cardiovascular or cerebrovascular risk over time. Metabolic changes are of particular concern patients with pre-existing risk factors, such as diabetes, obesity, or hyperlipidemia (e.g., hypercholesterolemia or hypertriglyceridemia). All patients should be informed of the importance of maintaining a nutritionally balanced diet during treatment with an antipsychotic. Clinical monitoring of weight and serum lipid profiles is recommended during aripiprazole treatment. When treating pediatric patients, weight gain should be assessed against the expected normal growth rate.

    Tardive dyskinesia

    A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. 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 inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products 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 antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment. There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, 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, aripiprazole 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 1) who suffer from a chronic illness that is known to respond to antipsychotic drugs, and 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment 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 in a patient on aripiprazole, drug discontinuation should be considered. However, some patients may require treatment with aripiprazole despite the presence of the syndrome. A rare but potentially fatal syndrome, neuroleptic malignant syndrome (NMS), may occur and requires immediate drug discontinuation.

    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. Pseudoparkinsonism was reported infrequently during clinical trial evaluation of aripiprazole; therefore, the drug should be used with caution in patients with Parkinson's disease because of the possible development of extrapyramidal symptoms. However, atypical antipsychotics like aripiprazole are less likely to interfere with treatments for Parkinson's disease than traditional antipsychotic agents.

    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 aripiprazole 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.

    Poor metabolizers

    Dosage adjustment of aripiprazole is recommended in known CYP2D6 poor metabolizers (CYP2D6 PMs) due to high aripiprazole concentrations. Approximately 8% of Caucasians and 3% to 8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers.

    Abrupt discontinuation

    When discontinuing treatment with antipsychotic or antidepressant treatment, the clinician should recognize that abrupt discontinuation of immediate-release dose forms in some patients can cause adverse symptoms. While immediate discontinuation of an antipsychotic treatment may be acceptable for some patients, more gradual discontinuation may be most appropriate for others. With extended-release injections, rate-limited elimination of aripiprazole occurs following any given dose.

    Dementia, geriatric, stroke

    Placebo-controlled studies of immediate-release dosage forms of aripiprazole in patients with schizophrenia, bipolar mania, or major depressive disorder did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience and pharmacokinetic data have not identified differences in responses between the elderly and younger adult patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Antipsychotics are not approved for the treatment of dementia-related psychosis in elderly patients. In April 2005 the FDA mandated that all manufacturers of atypical antipsychotics include a boxed warning to the labeling indicating that increased death rates (1.6 to 1.7 times that of placebo) have been noted in this patient population receiving atypical antipsychotics. Death typically occurred due to heart failure, sudden death, or infections (primarily pneumonia). Of 17 placebo controlled trials (n = 5,106) performed with olanzapine, aripiprazole, risperidone, or quetiapine in elderly patients with dementia-related psychosis, 15 showed numerical increases in mortality in the active compared to the placebo-treated patients. In aripiprazole placebo-controlled trials of dementia-related psychosis, there was an increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in aripiprazole-treated patients (mean age 84 years; range 78 to 88 years). In 1 study, there was a statistically significant dose response relationship for cerebrovascular adverse events in patients treated with aripiprazole. In a 10-week placebo-controlled study of aripiprazole in elderly patients with psychosis associated with Alzheimer's dementia, 3.8% (4 of 105 patients) of aripiprazole-treated patients died compared to no deaths in placebo treated patients during, or within 30 days after, termination of the double-blind portion of the study. Three of the patients died following discontinuation of aripiprazole with reported cause of death due to pneumonia, heart failure, or shock and the fourth patient died following hip surgery while in the double-blind phase of the study. 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. In addition, avoidance of aripiprazole is recommended in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: delirium (possible new-onset or worsening delirium) and dementia (adverse CNS effects). There is an increased risk of stroke and greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics, and 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. The Panel recommends avoiding 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 additional falls; if an antipsychotic must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. 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, aripiprazole appears less likely to precipitate a worsening of symptoms than most other antipsychotics and is excluded from the recommendation. Because antipsychotics can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. 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 that meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. There is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. Therefore, identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic. To initiate antipsychotic therapy, behavioral symptoms must be a danger to self or others and are either 1) due to mania or psychosis or 2) the plan of care includes documentation of attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less with evaluation and documentation within 7 days which identifies and addresses contributors/causes. For acute conditions persisting beyond 7 days, pertinent 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 include monitoring that ensures the behavioral symptoms are not due to a treatable or correctable medical condition, are not due to correctable environmental or treatable psychological stressors alone, and provides clearly documented evidence of persistence. The LTCF must evaluate the appropriateness of the antipsychotic during or within 2 weeks of admission for a newly admitted resident on an antipsychotic. In all cases, the lowest possible dose and shortest duration should be prescribed. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Monitoring of antipsychotics should include evaluation of ongoing effectiveness, rationale for use, and potential adverse effects (e.g., anticholinergic effects, neurological symptoms, metabolic syndrome, cardiac effects). Antipsychotics are subject to periodic review for effectiveness, necessity, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    Labor, neonates, obstetric delivery, pregnancy

    Aripiprazole is recommended for use during pregnancy only when the benefits to the mother outweigh the potential risks to the fetus. Animal studies have shown evidence of developmental toxicity, including possible teratogenicity, and an increase in stillbirths. Neonates exposed to antipsychotics during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms after delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. Symptoms have ranged from self-limiting to those requiring 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. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics. More information may be obtained by calling the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visiting the website at womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry. It is not clear if aripiprazole, through its effect on prolactin, would affect labor or obstetric delivery.

    Breast-feeding

    Aripiprazole is excreted into human breast milk; milk to plasma ratios of approximately 0.18 to 0.2 have been reported. According to the manufacturer, a decision should be made to discontinue breast-feeding or discontinue the drug, taking into account the importance of drug therapy to the mother. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding. However, because there is a lack of experience with aripiprazole during breast-feeding, other agents may be preferred especially while nursing a newborn or preterm infant. Alternate medications for consideration include atypical agents such as olanzapine or quetiapine. 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 ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Phenylketonuria

    Aripiprazole orally disintegrating tablets (i.e., Abilify Discmelt) should be used cautiously in patients with phenylketonuria, as the tablets contain aspartame, a source of phenylalanine. Each 10 mg orally disintegrating tablet contains 1.12 mg of phenylalanine and each 15 mg orally disintegrating tablet contains 1.68 mg of phenylalanine.

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 0.1-0.9
    seizures / Delayed / 0-0.2
    rhabdomyolysis / Delayed / 0-0.1
    atrial fibrillation / Early / 0-0.1
    cardiac arrest / Early / 0-0.1
    atrial flutter / Early / 0-0.1
    myocardial infarction / Delayed / 0-0.1
    AV block / Early / 0-0.1
    suicidal ideation / Delayed / Incidence not known
    stroke / Early / Incidence not known
    diabetic ketoacidosis / Delayed / Incidence not known
    neuroleptic malignant syndrome / Delayed / Incidence not known
    tardive dyskinesia / Delayed / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    laryngospasm / Rapid / Incidence not known

    Moderate

    hyperglycemia / Delayed / 0-17.6
    constipation / Delayed / 2.0-11.0
    blurred vision / Early / 3.0-8.0
    fecal incontinence / Early / 5.0-5.0
    sinus tachycardia / Rapid / 2.0-2.0
    myoclonia / Delayed / 0.1-1.0
    orthostatic hypotension / Delayed / 0.2-1.0
    memory impairment / Delayed / 0.1-0.9
    delirium / Early / 0.1-0.9
    peripheral edema / Delayed / 0.1-0.9
    hypotension / Rapid / 0.1-0.9
    urinary retention / Early / 0.1-0.9
    hypoglycemia / Early / 0.1-0.9
    myasthenia / Delayed / 0.1-0.9
    dyspnea / Early / 0.1-0.9
    photophobia / Early / 0.1-0.9
    elevated hepatic enzymes / Delayed / 0.1-0.9
    hypertension / Early / 0.1-0.9
    chest pain (unspecified) / Early / 0.1-0.9
    palpitations / Early / 0.1-0.9
    hyponatremia / Delayed / 0.1-0.9
    hypokalemia / Delayed / 0.1-0.9
    impotence (erectile dysfunction) / Delayed / 0.1-0.9
    sleep-related behaviors / Early / 0-0.1
    hyperprolactinemia / Delayed / 0-0.1
    hyperthermia / Delayed / 0-0.1
    hyperbilirubinemia / Delayed / 0-0.1
    hepatitis / Delayed / 0-0.1
    jaundice / Delayed / 0-0.1
    angina / Early / 0-0.1
    QT prolongation / Rapid / 0-0.1
    thrombocytopenia / Delayed / 0-0.1
    priapism / Early / 0-0.1
    urinary incontinence / Early / 1.0
    confusion / Early / Incidence not known
    impaired cognition / Early / Incidence not known
    impulse control symptoms / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    hyperlipidemia / Delayed / Incidence not known

    Mild

    headache / Early / 0-27.0
    weight gain / Delayed / 2.2-26.3
    drowsiness / Early / 3.0-23.0
    agitation / Early / 19.0-19.0
    insomnia / Early / 0-18.0
    fatigue / Early / 2.0-17.0
    anxiety / Delayed / 17.0-17.0
    nausea / Early / 8.0-15.0
    vomiting / Early / 3.0-14.0
    dizziness / Early / 3.0-10.0
    dyspepsia / Early / 9.0-9.0
    fever / Early / 4.0-9.0
    pharyngitis / Delayed / 3.0-9.0
    appetite stimulation / Delayed / 3.0-7.0
    restlessness / Early / 1.0-6.0
    hypersalivation / Early / 4.0-6.0
    lethargy / Early / 3.0-5.0
    xerostomia / Early / 5.0-5.0
    dental pain / Delayed / 4.0-4.0
    diarrhea / Early / 4.0-4.0
    arthralgia / Delayed / 1.0-4.0
    musculoskeletal pain / Early / 1.0-4.0
    abdominal pain / Early / 3.0-3.0
    cough / Delayed / 3.0-3.0
    irritability / Delayed / 2.0-2.0
    myalgia / Early / 2.0-2.0
    rash (unspecified) / Early / 0-2.0
    epistaxis / Delayed / 2.0-2.0
    libido decrease / Delayed / 0.1-0.9
    gastroesophageal reflux / Delayed / 0.1-0.9
    nocturia / Early / 0.1-0.9
    hyperhidrosis / Delayed / 0.1-0.9
    photosensitivity / Delayed / 0.1-0.9
    pruritus / Rapid / 0.1-0.9
    hirsutism / Delayed / 0.1-0.9
    alopecia / Delayed / 0.1-0.9
    nasal congestion / Early / 0.1-0.9
    syncope / Early / 0.2-0.5
    somnambulism / Early / 0-0.1
    libido increase / Delayed / 0-0.1
    urticaria / Rapid / 0-0.1
    diplopia / Early / 0-0.1
    gynecomastia / Delayed / 0-0.1
    amenorrhea / Delayed / 0-0.1
    menstrual irregularity / Delayed / 0-0.1
    mastalgia / Delayed / 0-0.1
    orgasm dysfunction / Delayed / 0-0.1
    asthenia / Delayed / 1.0
    weight loss / Delayed / 1.0
    anorexia / Delayed / 1.0
    injection site reaction / Rapid / 1.0
    emotional lability / Early / Incidence not known
    hypothermia / Delayed / Incidence not known
    hiccups / Early / Incidence not known

    DRUG INTERACTIONS

    Abarelix: Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as aripiprazole.
    Acarbose: Patients taking alpha-glucosidase inhibitors should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Acebutolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Acetaminophen; Butalbital: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Acetaminophen; Butalbital; Caffeine: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Acetaminophen; Butalbital; Caffeine; Codeine: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Acetaminophen; Dextromethorphan; Doxylamine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics.
    Acetaminophen; Dichloralphenazone; Isometheptene: Drugs that can cause CNS depression inlcuding dichloralphenazone, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Acetaminophen; Diphenhydramine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as diphenhydramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Acetaminophen; Pentazocine: Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with atypical antipsycotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
    Acetaminophen; Tramadol: Concurrent use of tramadol and aripiprazole should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and aripiprazole. Similar precautions apply to combination products containing tramadol such as acetaminophen; tramadol.
    Acrivastine; Pseudoephedrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Albiglutide: Patients taking incretin mimetics should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Changes in lipid profiles and weight may also aggravate diabetes or associated conditions or complications. Temporal associations of atypical antipsychotic therapy with the aggravation or new onset of diabetes mellitus have been reported.
    Albuterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Albuterol; Ipratropium: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Aldesleukin, IL-2: Because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as aldesleukin, IL-2. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions, particularly CNS effects. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Patients developing mood disturbances, moderate to severe lethargy/somnolence while on aldesleukin should seek evaluation from their health care provider.
    Alfuzosin: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval.
    Aliskiren; Amlodipine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Alogliptin: Patients taking alogliptin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alogliptin; Metformin: Patients taking alogliptin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Alogliptin; Pioglitazone: Patients taking alogliptin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. Atypical antipsychotics have been associated with causing hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. In addition, because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as pioglitazone may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in oral aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days.because aripiprazole blood concentrations decline and may become suboptimal.
    Alpha-glucosidase Inhibitors: Patients taking alpha-glucosidase inhibitors should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Alprazolam: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Amiodarone: Because both amiodarone and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as amiodarone. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Amitriptyline: Combination therapy with aripiprazole and tricyclic antidepressants should be approached with caution and close monitoring. Aripiprazole has a risk for QT prolongation and torsade de pointes, and tricyclics at elevated serum concentrations may produce clinically significant prolongation of the QTc interval. In addition, there is potential for other interactions, such as augmentation of anticholinergic effects.
    Amitriptyline; Chlordiazepoxide: Combination therapy with aripiprazole and tricyclic antidepressants should be approached with caution and close monitoring. Aripiprazole has a risk for QT prolongation and torsade de pointes, and tricyclics at elevated serum concentrations may produce clinically significant prolongation of the QTc interval. In addition, there is potential for other interactions, such as augmentation of anticholinergic effects. Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Amlodipine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Atorvastatin: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Benazepril: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Olmesartan: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Telmisartan: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Valsartan: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amobarbital: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Amoxapine: Use caution during co-administration of amoxapine and aripiprazole. 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: Because both clarithromycin and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as clarithromycin. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Amoxicillin; Clarithromycin; Omeprazole: Because both clarithromycin and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as clarithromycin. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Amphetamine: Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Amphetamine; Dextroamphetamine: Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Amphetamines: Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Amprenavir: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as amprenavir or fosamprenavir. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Amyl Nitrite: Administration of nitrates such as amyl nitrite to patients receiving other hypotension-producing agents, such as antipsychotics, can cause additive hypotensive or orthostatic effects.
    Anagrelide: Caution is advised if aripiprazole is administered with anagrelide. Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. 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. QT prolongation has also occurred during therapeutic use of aripiprazole and following overdose.
    Angiotensin II receptor antagonists: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Angiotensin-converting enzyme inhibitors: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Apomorphine: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 210 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. 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.
    Aprepitant, Fosaprepitant: Use caution if aripiprazole and multi-day regimens of oral aprepitant are used concurrently, and monitor for an increase in aripiprazole-related adverse effects, including QT prolongation and torsade de pointes (TdP), for several days after administration. Aripiprazole 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 aripiprazole. 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: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Armodafinil: In vitro data indicate that armodafinil is an inducer of CYP3A4/5 isoenzymes. Decreased blood levels of aripiprazole are expected when the drug is coadministered with inducers of CYP3A4, such as armodafinil. A dosage adjustment of aripiprazole may be necessary when these drugs are used concomitantly, and conversely, when armodafinil is discontinued in a patient taking aripiprazole.
    Arsenic Trioxide: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
    Artemether; Lumefantrine: Because both artemether; lumefantrine and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as artemether; lumefantrine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if a potent CYP2D6 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Asenapine: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Asenapine 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.
    Aspirin, ASA; Butalbital; Caffeine: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Atazanavir: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as atazanavir. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Atazanavir; Cobicistat: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as atazanavir. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. The plasma concentrations of aripiprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness and extrapyramidal symptoms, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while aripiprazole is a CYP3A4 and CYP2D6 substrate.
    Atenolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Atenolol; Chlorthalidone: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Atomoxetine: For both aripiprazole and atomoxetine, QT prolongation has occurred during therapeutic use and following overdose. In addition, atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Caution is recommended if these drugs are administered concurrently.
    Atropine; Difenoxin: Concurrent administration of diphenoxylate/difenoxin with aripiprazole can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Diphenoxylate: Concurrent administration of diphenoxylate/difenoxin with aripiprazole can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Azithromycin: Due to the risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering aripiprazole with azithromycin. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. There have also been case reports of QT prolongation and TdP with the use of azithromycin in post-marketing reports.
    Barbiturates: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Basiliximab: Because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as basiliximab. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Bedaquiline: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. 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. Coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Bendroflumethiazide; Nadolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Benzodiazepines: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Benzphetamine: Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Beta-adrenergic blockers: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Betaxolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Bexarotene: Because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as bosentan may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. Due to aripiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: 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 with metronidazole include aripiprazole.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: 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 with metronidazole include aripiprazole.
    Bisoprolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Bisoprolol; Hydrochlorothiazide, HCTZ: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Boceprevir: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as boceprevir. In adults receiving 300 mg or 400 mg of the extended-release aripiprazole injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Bosentan: Bosentan is an inducer of CYP3A4 enzymes, and may decrease plasma concentrations of drugs metabolized by these enzymes including aripiprazole.
    Brexpiprazole: Concurrent use of brexpiprazole and aripiprazole should be avoided. Aripiprazole and brexpiprazole are both atypical antipsychotics of the dopamine system stabilizer subclass and have similar mechanisms of action. In addition, the risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use.
    Brimonidine; Timolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Bromocriptine: 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.
    Brompheniramine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Carbetapentane; Phenylephrine: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Dextromethorphan; Guaifenesin: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Guaifenesin; Hydrocodone: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Hydrocodone; Pseudoephedrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Pseudoephedrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Budesonide; Formoterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Buprenorphine: Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of aripiprazole and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. 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 aripiprazole 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: Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of aripiprazole and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. 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 aripiprazole 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.
    Bupropion: Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as aripiprazole and risperidone, should be approached with caution. Dosage reductions of aripiprazole may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients.
    Bupropion; Naltrexone: Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as aripiprazole and risperidone, should be approached with caution. Dosage reductions of aripiprazole may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients.
    Buspirone: The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Butabarbital: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Butorphanol: Concomitant use of butorphanol with other CNS depressants, such as aripiprazole, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
    Canagliflozin: Patients taking canagliflozin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Canagliflozin; Metformin: Patients taking canagliflozin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Carbamazepine: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as carbamazepine, is added to aripiprazole therapy. Concurrent use of carbamazepine (200 mg twice daily) and aripiprazole (30 mg/day) resulted in a decrease in Cmax and AUC values of aripiprazole and its active metabolite by about 70%. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Carbetapentane; Chlorpheniramine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. 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; Chlorpheniramine; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. 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; Diphenhydramine; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as diphenhydramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. 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: 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: 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: 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: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbetapentane; Pseudoephedrine: 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: Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbidopa; Levodopa: Antipsychotic agents may inhibit the clinical antiparkinsonian response to levodopa by blocking dopamine receptors in the brain. In general, however, the 'atypical antipsychotics' are less likely to interfere with these therapies than traditional antipsychotic agents (e.g., phenothiazines). Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments. In general, experts consider quetiapine the atypical antipsychotic of choice in Parkinson's patients due to a lower incidence of extrapyramidal symptoms, although the choice of antipsychotic medication must always be made on a case-by-case decision.
    Carbidopa; Levodopa; Entacapone: Antipsychotic agents may inhibit the clinical antiparkinsonian response to levodopa by blocking dopamine receptors in the brain. In general, however, the 'atypical antipsychotics' are less likely to interfere with these therapies than traditional antipsychotic agents (e.g., phenothiazines). Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments. In general, experts consider quetiapine the atypical antipsychotic of choice in Parkinson's patients due to a lower incidence of extrapyramidal symptoms, although the choice of antipsychotic medication must always be made on a case-by-case decision. Atypical antipsychotics are central dopamine antagonists and may inhibit the clinical response to antiparkinsonian agents with dopamine agonist properties by blocking dopamine receptors in the brain. Due to the CNS depressant effects of atypical antipsychotics, additive drowsiness may occur with Parkinson's treatments like entacapone or tolcapone. In general, atypical antipsychotics are less likely to interfere with these therapies than traditional antipsychotic agents.
    Carbinoxamine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Hydrocodone; Phenylephrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Phenylephrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Pseudoephedrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Cariprazine: Similar to other antipsychotics, cariprazine 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 cariprazine 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.
    Carteolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Carvedilol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Celecoxib: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as celecoxib, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Central-acting adrenergic agents: Due to aripiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
    Ceritinib: Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with ceritinib include aripiprazole. Periodically monitor electrocardiograms (EGCs) and electrolytes; therapy interruption, dose reduction, or discontinuation may be required.
    Cetrorelix: Antipsychotic-induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs.
    Charcoal: Aripiprazole absorption is reduced when activated charcoal is coadministered within an hour of a 15 mg dosage, resulting in a decrease in aripiprazole AUC and Cmax by roughly 50%. Concomitant administration of aripiprazole with activated charcoal is not recommended. However, administration of activated charcoal may be appropriate in certain aripiprazole overdose situations.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Chloramphenicol: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as chloramphenicol. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorcyclizine: Additive CNS effects like drowsiness may be seen when combining sedating H1-blockers with atypical antipsychotics.
    Chlordiazepoxide: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Chlordiazepoxide; Clidinium: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Chloroquine: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Chloroquine administration is associated with an increased risk of QT prolongation and torsades de pointes (TdP). The need to coadminister chloroquine with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits and should be avoided when possible. In addition, because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chloroquine or hydroxychloroquine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Codeine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Dextromethorphan: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Hydrocodone: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Hydrocodone; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpheniramine; Pseudoephedrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as chlorpheniramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Chlorpromazine: Concurrent use of chlorpromazine with aripiprazole should be approached with caution and careful monitoring due to a possible risk o f QT prolongation. In addition, chlorpromazine is a CYP2D6 inhibitor. A dosage reduction of aripiprazole may be clinically warranted in patients receiving chlorpromazine and caution is advisable when aripiprazole is given in combination with other antipsychotics. 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. 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.
    Cimetidine: Because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as cimetidine. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions.
    Cinacalcet: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potent inhibitors of CYP2D6 such as cinacalcet, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In adults receiving 300 mg or 400 mg of Abilify Maintena extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if a potent CYP2D6 inhibitor is used for more than 14 days. Adults receiving 662 mg or 882 mg of Aristada extended-release injection every 4 weeks should have their Aristada dose reduced to the next lower strength if a potent CYP2D6 inhibitor is used for more than 14 days. No dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. For patients receiving Aristada 882 mg every 6 weeks, reduce the dose to 441 mg every 4 weeks. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Avoid use of combination therapy with a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days in patients receiving 662 mg or 882 mg of Aristada; no dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated).
    Ciprofloxacin: Caution is advised when administering aripiprazole with ciprofloxacin, as use of these drugs together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In addition, rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance.
    Cisapride: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for QT prolongation or torsade de pointes (TdP), concurrent use is contraindicated.
    Citalopram: Because both citalopram and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), this combination should be used cautiously and with close monitoring. In addition, citalopram is a weak inhibitor of CYP2D6, and increased plasma concentrations of antipsychotics partially metabolized via CYP2D6, such as aripiprazole, may occur. Decreased metabolism of aripiprazole may lead to clinically important adverse reactions, such as extrapyramidal symptoms.
    Clarithromycin: Because both clarithromycin and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as clarithromycin. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Clemastine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Clobazam: A dosage reduction of CYP2D6 substrates, such as aripiprazole, paliperidone, iloperidone, olanzapine, or risperidone may be necessary during co-administration of clobazam. Limited in vivo data suggest that clobazam is an inhibitor of CYP2D6. In addition, benzodiazepines such as clobazam should be combined cautiously with atypical 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.
    Clomipramine: Combination therapy with aripiprazole and tricyclic antidepressants should be approached with caution and close monitoring. Aripiprazole has a risk for QT prolongation and torsade de pointes, and tricyclics at elevated serum concentrations may produce clinically significant prolongation of the QTc interval. In addition, there is potential for other interactions, such as augmentation of anticholinergic effects.
    Clonazepam: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Clorazepate: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Clozapine: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Clozapine is an atypical antipsychotic 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.
    Cobicistat: The plasma concentrations of aripiprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness and extrapyramidal symptoms, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while aripiprazole is a CYP3A4 and CYP2D6 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: The plasma concentrations of aripiprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness and extrapyramidal symptoms, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while aripiprazole is a CYP3A4 and CYP2D6 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: The plasma concentrations of aripiprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness and extrapyramidal symptoms, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while aripiprazole is a CYP3A4 and CYP2D6 substrate.
    Codeine; Phenylephrine; Promethazine: Both promethazine and aripiprazole are associated with a possible risk for QT prolongation; therefore, caution is advisable during coadministration. In addition, because aripiprazole is partially metabolized by CYP2D6, patients should be monitored for aripiprazole-related adverse reactions during concurrent use of a CYP2D6 inhibitor such as promethazine. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP2D6 inhibitor. Coadministration of phenothiazines such as promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Codeine; Promethazine: Both promethazine and aripiprazole are associated with a possible risk for QT prolongation; therefore, caution is advisable during coadministration. In addition, because aripiprazole is partially metabolized by CYP2D6, patients should be monitored for aripiprazole-related adverse reactions during concurrent use of a CYP2D6 inhibitor such as promethazine. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP2D6 inhibitor. Coadministration of phenothiazines such as promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    COMT inhibitors: Atypical antipsychotics are central dopamine antagonists and may inhibit the clinical response to antiparkinsonian agents with dopamine agonist properties by blocking dopamine receptors in the brain. Due to the CNS depressant effects of atypical antipsychotics, additive drowsiness may occur with Parkinson's treatments like entacapone or tolcapone. In general, atypical antipsychotics are less likely to interfere with these therapies than traditional antipsychotic agents.
    Conivaptan: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as conivaptan. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Crizotinib: Because both crizotinib and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, concomitant use of crizotinib and aripiprazole may result in increased aripiprazole concentrations. Crizotinib is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while aripiprazole is a CYP3A4 substrate. Monitor patients for toxicity with coadministration. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response.
    Cyclizine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Cyclobenzaprine: Caution is advised when administering aripiprazole with cyclobenzaprine, as use of these drugs together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Cyclobenzaprine is structurally similar to tricyclic antidepressants. Tricyclic antidepressants have been reported to prolong the QT interval, especially when given in excessive doses (or in overdosage settings). Cyclobenzaprine is associated with a possible risk of QT prolongation and TdP, particularly in the event of acute overdose.
    Cyproheptadine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Dalfopristin; Quinupristin: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as dalfopristin; quinupristin. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Danazol: Because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as danazol. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Dapagliflozin: Patients taking dapagliflozin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Dapagliflozin; Metformin: Patients taking dapagliflozin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Darunavir: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as darunavir. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Darunavir; Cobicistat: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as darunavir. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. The plasma concentrations of aripiprazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as drowsiness and extrapyramidal symptoms, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while aripiprazole is a CYP3A4 and CYP2D6 substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Because ritonavir (including lopinavir; ritonavir) and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), these combinations should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as ritonavir. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Dasatinib: Because both dasatinib and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as dasatinib. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response.
    Daunorubicin: Aripiprazole is associated with a possible risk for QT prolongation and torsade de pointes (TdP), and should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risk for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of these agents; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Degarelix: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Delavirdine: Because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as delavirdine. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Desipramine: Combination therapy with aripiprazole and tricyclic antidepressants should be approached with caution and close monitoring. Aripiprazole has a risk for QT prolongation and torsade de pointes, and tricyclics at elevated serum concentrations may produce clinically significant prolongation of the QTc interval. In addition, there is potential for other interactions, such as augmentation of anticholinergic effects.
    Dexamethasone: Because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as dexamethasone may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Dexchlorpheniramine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Dexmethylphenidate: Concurrent use of antipsychotics and dexmethylphenidate should generally be avoided. Antipsychotics and stimulants may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Dexmethylphenidate is thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of dexmethylphenidate. Pimozide should not be used to treat motor or phonic tics in patients taking drugs that may cause tics such as dexmethylphenidate until such patients have been withdrawn from the drug to determine whether or not the drug, rather than Tourette's Disorder, is responsible for the tics. Methylphenidate is an inhibitor of dopamine reuptake. Pharmacodynamic interactions may occur between methylphenidate and dopamine antagonists such as antipsychotics. Patients receiving methylphenidate in combination with an antipsychotic should be monitored for a decrease in clinical effectiveness of either agent.
    Dextroamphetamine: Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Dextromethorphan; Diphenhydramine; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as diphenhydramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Dextromethorphan; Promethazine: Both promethazine and aripiprazole are associated with a possible risk for QT prolongation; therefore, caution is advisable during coadministration. In addition, because aripiprazole is partially metabolized by CYP2D6, patients should be monitored for aripiprazole-related adverse reactions during concurrent use of a CYP2D6 inhibitor such as promethazine. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP2D6 inhibitor. Coadministration of phenothiazines such as promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Dextromethorphan; Quinidine: According to the manufacturer of dextromethorphan; quinidine, the concurrent use of dextrometherophan; quinidine with drugs that are both 2D6 substrates and prolong the QT interval, such as aripiprazole, is contraindicated. Both quinidine and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP). During coadministration of aripiprazole and quinidine alone, there may be an increase in aripiprazole concentrations due to potent inhibition of CYP2D6 by quinidine, which can increase the risk for QT prolongation or other serious aripiprazole-related adverse effects. In one evaluation, concurrent use of quinidine and oral aripiprazole resulted in an increase in the AUC of aripiprazole of 112% and a decrease in the AUC of its active metabolite by 35%. The manufacturer of aripiprazole recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP2D6 such as quinidine. The manufacturer also recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a combination of CYP3A4 and CYP2D6 inhibitors. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if a strong CYP2D6 inhibitor is used for more than 14 days. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP2D6 inhibitor for more than 14 days. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. For patients receiving 882 mg of Aristada every 6 weeks, the next lower strength should be 441 mg administered every 4 weeks. In adults receiving Aristada 662 mg or 882 mg, combined use of a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days should be avoided; no dose adjustment is needed in patients taking 441 mg, if tolerated.
    Diazepam: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Diazoxide: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Diltiazem: Because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as diltiazem. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Due to aripiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
    Dimenhydrinate: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Diphenhydramine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as diphenhydramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Diphenhydramine; Hydrocodone; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as diphenhydramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Diphenhydramine; Ibuprofen: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as diphenhydramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Diphenhydramine; Phenylephrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as diphenhydramine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Disopyramide: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Aripiprazole should be used cautiously and with close monitoring with disopyramide.
    Dofetilide: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Because of the potential for QT prolongation or TdP, concurrent use is contraindicated.
    Dolasetron: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Aripiprazole should be used cautiously and with close monitoring with dolasetron.
    Donepezil: 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 aripiprazole.
    Donepezil; Memantine: 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 aripiprazole.
    Dorzolamide; Timolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Doxazosin: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Doxepin: Combination therapy with aripiprazole and tricyclic antidepressants should be approached with caution and close monitoring. Aripiprazole has a risk for QT prolongation and torsade de pointes, and tricyclics at elevated serum concentrations may produce clinically significant prolongation of the QTc interval. In addition, there is potential for other interactions, such as augmentation of anticholinergic effects.
    Doxorubicin: Aripiprazole is associated with a possible risk for QT prolongation and torsade de pointes (TdP), and should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risk for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of these agents; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Doxylamine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics.
    Doxylamine; Pyridoxine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics.
    Dronabinol, THC: 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: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. 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. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated.
    Droperidol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
    Dulaglutide: Patients taking incretin mimetics should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Changes in lipid profiles and weight may also aggravate diabetes or associated conditions or complications. Temporal associations of atypical antipsychotic therapy with the aggravation or new onset of diabetes mellitus have been reported.
    Duloxetine: Because aripiprazole is partially metabolized by CYP2D6, increased aripiprazole plasma concentrations may occur during concurrent use of moderate inhibitors of CYP2D6, such as duloxetine. Decreased metabolism of aripiprazole may lead to clinically important adverse reactions, such as extrapyramidal symptoms. Mild inhibitors of CYP2D6, such as venlafaxine, are less likely to interact with aripiprazole.
    Echinacea: The metabolism of aripiprazole may be inhibited or induced by echinacea. Monitor for changes in efficacy or toxicity when echinacea is coadministered with drugs that are metabolized by CYP3A4, including aripiprazole, until more data are available.
    Efavirenz: Although data are limited, coadministration of efavirenz and aripiprazole may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. QT prolongation has also occurred during therapeutic use of aripiprazole and following overdose. In addition, decreased aripiprazole blood levels are expected when aripiprazole is coadministered with inducers of CYP3A4, such as efavirenz. Monitor the patient carefully for toxicity and efficacy if these agents are used in combination. Dosage adjustments of aripiprazole may be clinically warranted in some patients.
    Efavirenz; Emtricitabine; Tenofovir: Although data are limited, coadministration of efavirenz and aripiprazole may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. QT prolongation has also occurred during therapeutic use of aripiprazole and following overdose. In addition, decreased aripiprazole blood levels are expected when aripiprazole is coadministered with inducers of CYP3A4, such as efavirenz. Monitor the patient carefully for toxicity and efficacy if these agents are used in combination. Dosage adjustments of aripiprazole may be clinically warranted in some patients.
    Elbasvir; Grazoprevir: Administering aripiprazole with elbasvir; grazoprevir may result in elevated aripiprazole plasma concentrations. Aripiprazole is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eliglustat: Coadminister aripiprazole and eliglustat cautiously and with close monitoring; there may be an increased risk of QT prolongation and/or aripiprazole-associated adverse effects. If coadministration is necessary, consider reducing the aripiprazole dosage and titrating to clinical effect. The aripiprazole product label recommends decreasing the antipsychotic dose by at least one-half of the usual dose when used with a potential CYP2D6 inhibitor, such as eliglustat, except when an indicated dose is being used as adjunct treatment for major depressive disorder. If eliglustat is discontinued while the patient is still taking aripiprazole, monitor for antipsychotic efficacy and increase the dose as necessary. Eliglustat is CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Aripiprazole is a CYP2D6 substrate associated with a potential for QT prolongation with both therapeutic use and overdose. Coadministration of aripiprazole and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of aripiprazole, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
    Empagliflozin: Patients taking empagliflozin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Empagliflozin; Linagliptin: Patients taking empagliflozin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking linagliptin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted.The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Empagliflozin; Metformin: Patients taking empagliflozin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Rilpivirine should be used cautiously and with close monitoring with aripiprazole.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Rilpivirine should be used cautiously and with close monitoring with aripiprazole.
    Enalapril; Felodipine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Entacapone: Atypical antipsychotics are central dopamine antagonists and may inhibit the clinical response to antiparkinsonian agents with dopamine agonist properties by blocking dopamine receptors in the brain. Due to the CNS depressant effects of atypical antipsychotics, additive drowsiness may occur with Parkinson's treatments like entacapone or tolcapone. In general, atypical antipsychotics are less likely to interfere with these therapies than traditional antipsychotic agents.
    Epirubicin: Aripiprazole is associated with a possible risk for QT prolongation and torsade de pointes (TdP), and should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risk for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of these agents; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Eplerenone: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Epoprostenol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Eribulin: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erythromycin: Because both erythromycin and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is partially metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as erythromycin. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP3A4 inhibitor.
    Erythromycin; Sulfisoxazole: Because both erythromycin and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is partially metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as erythromycin. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP3A4 inhibitor.
    Escitalopram: Because both escitalopram and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), this combination should be used cautiously and with close monitoring. In addition, escitalopram is a modest inhibitor of CYP2D6 and may decrease the clearance of CYP2D6 substrates including aripiprazole. Decreased metabolism of aripiprazole may lead to clinically important adverse reactions, such as extrapyramidal symptoms. Data from the manufacturer indicate no clinically significant pharmacokinetic changes to escitalopram with co-administration.
    Eslicarbazepine: In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as aripiprazole, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of aripiprazole if coadministered with eslicarbazepine. Dosage adjustments of aripirazole may be necessary.
    Esmolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Estazolam: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Eszopiclone: 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: Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use of alcohol or illicit drugs when prescribing CNS depressant medications. In many cases, the patient should receive a lower dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol.
    Ethotoin: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as ethotoin, phenytoin, or fosphenytoin, is added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Etravirine: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as etravirine, is added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Exenatide: Patients taking incretin mimetics should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Changes in lipid profiles and weight may also aggravate diabetes or associated conditions or complications. Temporal associations of atypical antipsychotic therapy with the aggravation or new onset of diabetes mellitus have been reported.
    Ezogabine: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Ezogabine has been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval. Aripiprazole should be used cautiously and with close monitoring with ezogabine.
    Famotidine: Coadministration of aripiprazole with famotidine decreases aripiprazole's solubility and rate of absorption. The Cmax of aripiprazole and the metabolite dehydroaripiprazole are decreased by 37% and 21%, respectively, and the AUC of aripiprazole and the dehydroaripiprazole metabolite are decreased by 13% and 15%, respectively. This interaction does not appear to cause clinically relevant effects and therefore no dosage adjustments are required.
    Famotidine; Ibuprofen: Coadministration of aripiprazole with famotidine decreases aripiprazole's solubility and rate of absorption. The Cmax of aripiprazole and the metabolite dehydroaripiprazole are decreased by 37% and 21%, respectively, and the AUC of aripiprazole and the dehydroaripiprazole metabolite are decreased by 13% and 15%, respectively. This interaction does not appear to cause clinically relevant effects and therefore no dosage adjustments are required.
    Felodipine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Fenoldopam: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Fingolimod: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. 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. Aripiprazole should be used cautiously and with close monitoring with fingolimod.
    Flecainide: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Aripiprazole should be used cautiously and with close monitoring with flecainide.
    Fluconazole: Concurrent use of aripiprazole and fluconazole is contraindicated due to the possible risk of QT prolongation and torsade de pointes (TdP) with each agent and the potential for fluconazole to increase plasma concentrations of aripiprazole through inhibition of CYP3A4, one of the metabolic pathways of aripiprazole.
    Fluoxetine: Because both fluoxetine and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, fluoxetine is a potent inhibitor of CYP2D6 and its metabolite is a moderate CYP3A4 inhibitor, which may result in decreased clearance of atypical antipsychotics that are CYP2D6 and CYP3A4 substrates including aripiprazole. Decreased metabolism of aripiprazole may lead to clinically important adverse reactions that are associated with antipsychotic use, such as extrapyramidal symptoms. The manufacturer recommends that the oral aripiprazole dose be reduced by one-half when co-administered with potent inhibitors of CYP3A4 or inhibitors of CYP2D6. In adult patients receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if a potent CYP2D6 inhibitor or CYP3A4 inhibitor is used for more than 14 days. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Because fluoxetine and its metabolite norfluoxetine inhibit both CYP3A4 and CYP2D6, a further reduction in aripiprazole dosage may be clinically warranted in some patients. It should be noted that aripiprazole dosage adjustments are not required when it is added as adjunctive treatment to antidepressants for major depressive disorder, provided that the manufacturer's dosing guidelines for this indication are followed. Currently available data indicate no clinically significant pharmacokinetic changes to fluoxetine with coadministration. The effects of fluoxetine on the metabolism of interacting drugs may persist for several weeks after discontinuation of fluoxetine because of its long elimination half-life.
    Fluoxetine; Olanzapine: Because both fluoxetine and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, fluoxetine is a potent inhibitor of CYP2D6 and its metabolite is a moderate CYP3A4 inhibitor, which may result in decreased clearance of atypical antipsychotics that are CYP2D6 and CYP3A4 substrates including aripiprazole. Decreased metabolism of aripiprazole may lead to clinically important adverse reactions that are associated with antipsychotic use, such as extrapyramidal symptoms. The manufacturer recommends that the oral aripiprazole dose be reduced by one-half when co-administered with potent inhibitors of CYP3A4 or inhibitors of CYP2D6. In adult patients receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if a potent CYP2D6 inhibitor or CYP3A4 inhibitor is used for more than 14 days. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Because fluoxetine and its metabolite norfluoxetine inhibit both CYP3A4 and CYP2D6, a further reduction in aripiprazole dosage may be clinically warranted in some patients. It should be noted that aripiprazole dosage adjustments are not required when it is added as adjunctive treatment to antidepressants for major depressive disorder, provided that the manufacturer's dosing guidelines for this indication are followed. Currently available data indicate no clinically significant pharmacokinetic changes to fluoxetine with coadministration. The effects of fluoxetine on the metabolism of interacting drugs may persist for several weeks after discontinuation of fluoxetine because of its long elimination half-life. Olanzapine is an atypical antipsychotics with a possible risk for QT prolongation and torsade de pointes (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.
    Fluphenazine: Fluphenazine,a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as aripiprazole. Co-administration of fluphenazine 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.
    Flurazepam: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Fluticasone; Salmeterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Fluticasone; Vilanterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Fluvoxamine: Fluvoxamine is a moderate inhibitor of CYP3A4, which may result in decreased clearance of atypical antipsychotics that are CYP3A4 substrates including aripiprazole. Decreased metabolism of aripiprazole may lead to clinically important adverse reactions that are associated with antipsychotic use, such as extrapyramidal symptoms.
    Food: Administering smoked marijuana to patients on antipsychotics may alter the plasma concentration, decrease the efficacy, or increase the adverse effects of the antipsychotic. Like tobacco smoke, components within marijuana smoke are inducers of CYP1A2, an isoenzyme responsible for the metabolism of two antipsychotics, clozapine and olanzapine. If marijuana smoking is begun or stopped in a patient on clozapine or olanzapine, the plasma concentrations of that antipsychotic may be decreased or increased, respectively. Further, marijuana has known psychoactive pharmacologic properties which may interfere with the actions of antipsychotic medications.
    Formoterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Formoterol; Mometasone: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Fosamprenavir: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as amprenavir or fosamprenavir. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Foscarnet: When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as aripiprazole. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). QT prolongation has also occurred during therapeutic use of aripiprazole and following overdose. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosphenytoin: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as ethotoin, phenytoin, or fosphenytoin, is added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Ganirelix: Antipsychotic-induced hyperprolactinemia results in down-regulatation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs.
    Gefitinib: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as gefitinib, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Gemifloxacin: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Aripiprazole should be used cautiously and with close monitoring with gemifloxacin
    Glimepiride; Pioglitazone: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. Atypical antipsychotics have been associated with causing hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. In addition, because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as pioglitazone may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in oral aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days.because aripiprazole blood concentrations decline and may become suboptimal.
    Glimepiride; Rosiglitazone: Aripiprazole has been associated with causing hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when aripiprazole is instituted.
    Glipizide; Metformin: Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Glyburide; Metformin: Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Glycopyrrolate; Formoterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Goserelin: Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with goserelin include aripiprazole. In addition, in the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia (e.g., some antipsychotics) should not be administered concomitantly with goserelin since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
    Granisetron: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Granisetron should be used cautiously and with close monitoring with aripiprazole
    Grapefruit juice: Grapefruit and grapefruit juice inhibit CYP3A4 metabolism in gut enterocytes, and therefore may decrease aripiprazole metabolism, resulting in increased blood concentrations of aripiprazole. Patients should not significantly adjust their intake of grapefruit or grapefruit juice while taking aripiprazole. As with drugs that significantly inhibit the CYP3A4 pathway, consideration should be given to altering the aripiprazole dose.
    Halofantrine: Because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as halofantrine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Halogenated Anesthetics: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Halogenated anesthetics can prolong the QT interval and should be used cautiously and with close monitoring with aripirazole.
    Haloperidol: Because both haloperidol and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, haloperidol is an inhibitor of CYP2D6. A dosage reduction of aripiprazole may be clinically warranted in patients receiving combination therapy with these agents. Although, according to the manufacturer of aripiprazole, no dosage adjustment is recommended in patients taking a CYP2D6 inhibitor who are receiving aripiprazole as adjunct treatment for major depressive disorder. Additive CNS effects can occur when aripiprazole is given in combination with other CNS depressants such as haloperidol. 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. 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.
    Histrelin: Antipsychotics may cause hyperprolactinemia and should not be administered concomitantly with GnRH analogs since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
    Hydantoins: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as ethotoin, phenytoin, or fosphenytoin, is added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Hydralazine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Hydralazine; Hydrochlorothiazide, HCTZ: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Hydralazine; Isosorbide Dinitrate, ISDN: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Hydrochlorothiazide, HCTZ; Metoprolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Hydrochlorothiazide, HCTZ; Propranolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Hydroxychloroquine: Avoid coadministration of hydroxychloroquine and aripiprazole. 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. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In addition, aripiprazole is metabolized by CYP2D6. If coadministration is unavoidable, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6 such as hydroxychloroquine, except those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended.
    Hydroxyzine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics.
    Ibutilide: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. 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. Ibutilide should be used cautiously and with close monitoring with aripiprazole.
    Idarubicin: Aripiprazole is associated with a possible risk for QT prolongation and torsade de pointes (TdP), and should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risk for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of these agents; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Idelalisib: Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with aripiprazole, a CYP3A substrate, as aripiprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. If these drugs must be used together, dose adjustments of aripiprazole are necessary. Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as idelalisib. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Iloperidone: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Iloperidone 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.
    Iloprost: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Imatinib, STI-571: Because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as imatinib, STI-571. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Imipramine: Combination therapy with aripiprazole and tricyclic antidepressants should be approached with caution and close monitoring. Aripiprazole has a risk for QT prolongation and torsade de pointes, and tricyclics at elevated serum concentrations may produce clinically significant prolongation of the QTc interval. In addition, there is potential for other interactions, such as augmentation of anticholinergic effects.
    Incretin Mimetics: Patients taking incretin mimetics should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Changes in lipid profiles and weight may also aggravate diabetes or associated conditions or complications. Temporal associations of atypical antipsychotic therapy with the aggravation or new onset of diabetes mellitus have been reported.
    Indacaterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Indacaterol; Glycopyrrolate: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Indinavir: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as indinavir. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Insulin Degludec; Liraglutide: Patients taking incretin mimetics should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Changes in lipid profiles and weight may also aggravate diabetes or associated conditions or complications. Temporal associations of atypical antipsychotic therapy with the aggravation or new onset of diabetes mellitus have been reported.
    Insulin Glargine; Lixisenatide: Patients taking incretin mimetics should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Changes in lipid profiles and weight may also aggravate diabetes or associated conditions or complications. Temporal associations of atypical antipsychotic therapy with the aggravation or new onset of diabetes mellitus have been reported.
    Insulins: Patients taking insulin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted.The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Isavuconazonium: Concomitant use of isavuconazonium with aripiprazole may result in increased serum concentrations of aripiprazole. Aripiprazole 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: 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.
    Isoniazid, INH: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as isoniazid, INH. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as rifampin, is added to aripiprazole therapy with subsequent adjustments based upon clinical response. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as isoniazid, INH. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Isoniazid, INH; Rifampin: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as rifampin, is added to aripiprazole therapy with subsequent adjustments based upon clinical response. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as isoniazid, INH. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Isradipine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Itraconazole: Caution is advised when administering itraconazole with drugs that are known to prolong that QT interval and are metabolized by CYP3A4, such as aripiprazole. Both aripiprazole and itraconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of itraconazole (a potent CYP3A4 inhibitor) with aripiprazole (a partial CYP3A4 substrate) may result in an elevated aripiprazole plasma concentrations and an increased risk for adverse events, including QT prolongation. If these drugs must be used together, the manufacturer recommends the oral dose of aripiprazole dose be reduced to one-half of the usual. If these drugs are given together, and the patient is a poor metabolizer of CYP2D6, the oral dose of aripiprazole should be decreased to a quarter of the usual dose. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. 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: Use caution when administering ivacaftor and aripiprazole concurrently. Ivacaftor is an inhibitor of CYP3A, and aripiprazole is a CYP3A substrate. Co-administration can increase aripiprazole exposure leading to increased or prolonged therapeutic effects and adverse events. If these agents are used in combination, carefully monitor patients for aripiprazole-related adverse reactions.
    Kava Kava, Piper methysticum: The German Commission E warns that any substances that act on the CNS, including psychotropic agents, may interact with kava kava. While the interactions can be pharmacodynamic in nature, 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 also possible.
    Ketoconazole: Increased aripiprazole blood levels are expected when given with potent inhibitors of CYP3A4 such as ketoconazole. Aripiprazole and ketoconazole are both associated with prolongation of the QT interval. The manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as ketoconazole; monitor for aripiprazole-related adverse reactions, including QT prolongation. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. Concurrent use of aripiprazole (15 mg single dose) and ketoconazole (200 mg/day for 14 days) resulted in an increase in the AUC of aripiprazole and its active metabolite by 63% and 77%, respectively. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injections who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Labetalol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Lamotrigine: Coadministration of aripiprazole and lamotrigine may slightly decrease lamotrigine plasma concentrations; however, this interaction is not expected to be clinically meaningful. During clinical trials, lamotrigine exposure was reduced approximately 10% in patients (n = 18) on a stable regimen of lamotrigine 100400 mg/day who received ariprazole 1030 mg/day for 7 days, followed by 30 mg/day for an additional 7 days.
    Lanreotide: Because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4. Lanreotide suppresses growth hormone secretion, which may cause a decrease in the metabolic clearance of drugs metabolized by CYP3A4. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response.
    Lapatinib: Because both lapatinib and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as lapatinib. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Lenvatinib: Aripiprazole should be used cautiously and with close monitoring with lenvatinib. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Leuprolide: Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include aripiprazole.
    Leuprolide; Norethindrone: Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include aripiprazole.
    Levalbuterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Levobetaxolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Levobunolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Levodopa: Antipsychotic agents may inhibit the clinical antiparkinsonian response to levodopa by blocking dopamine receptors in the brain. In general, however, the 'atypical antipsychotics' are less likely to interfere with these therapies than traditional antipsychotic agents (e.g., phenothiazines). Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments. In general, experts consider quetiapine the atypical antipsychotic of choice in Parkinson's patients due to a lower incidence of extrapyramidal symptoms, although the choice of antipsychotic medication must always be made on a case-by-case decision.
    Levofloxacin: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of torsade de pointes (TdP) have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
    Linagliptin: Patients taking linagliptin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted.The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Linagliptin; Metformin: Patients taking linagliptin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted.The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Liraglutide: Patients taking incretin mimetics should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Changes in lipid profiles and weight may also aggravate diabetes or associated conditions or complications. Temporal associations of atypical antipsychotic therapy with the aggravation or new onset of diabetes mellitus have been reported.
    Lisdexamfetamine: Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Lithium: Aripiprazole and lithium are associated with QT prolongation. Coadministration may increase the risk of QT prolongation; therefore, aripiprazole and lithium should be coadministered with caution and close monitoring. Some atypical antipsychotics, including aripiprazole, 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. Aripiprazole does not change the pharmacokinetic parameters of lithium.
    Lixisenatide: Patients taking incretin mimetics should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Changes in lipid profiles and weight may also aggravate diabetes or associated conditions or complications. Temporal associations of atypical antipsychotic therapy with the aggravation or new onset of diabetes mellitus have been reported.
    Long-acting beta-agonists: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Loop diuretics: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Loperamide: Loperamide should be used cautiously and with close monitoring with aripiprazole. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Coadministration my further increase the risk of QT prolongation and TdP.
    Loperamide; Simethicone: Loperamide should be used cautiously and with close monitoring with aripiprazole. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Coadministration my further increase the risk of QT prolongation and TdP.
    Lopinavir; Ritonavir: Because ritonavir (including lopinavir; ritonavir) and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), these combinations should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as ritonavir. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Loratadine: Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness when used concurrently with other CNS depressants such as antipsychotics.
    Loratadine; Pseudoephedrine: Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness when used concurrently with other CNS depressants such as antipsychotics.
    Lorazepam: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Loxapine: Caution is advisable during concurrent use of aripiprazole with other CNS depressants such as loxapine. 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. 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: Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of aripiprazole. If used together, the aripiprazole dose should be doubled over 1 to 2 weeks. Monitor the patient closely for antipsychotic efficacy; additional dosage increases should be based on clinical evaluation. If lumacaftor; ivacaftor therapy is later withdrawn, the ariprazole dosage should be reduced. Aripipirazole is a CYP3A substrate. Lumacaftor is a strong CYP3A inducer. Coadministration of aripiprazole (30 mg daily) with carbamazepine (200 mg twice daily), another strong CYP3A inducer, resulted in a 70% decrease in Cmax and AUC values of both aripiprazole and its active metabolite.
    Lumacaftor; Ivacaftor: Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of aripiprazole. If used together, the aripiprazole dose should be doubled over 1 to 2 weeks. Monitor the patient closely for antipsychotic efficacy; additional dosage increases should be based on clinical evaluation. If lumacaftor; ivacaftor therapy is later withdrawn, the ariprazole dosage should be reduced. Aripipirazole is a CYP3A substrate. Lumacaftor is a strong CYP3A inducer. Coadministration of aripiprazole (30 mg daily) with carbamazepine (200 mg twice daily), another strong CYP3A inducer, resulted in a 70% decrease in Cmax and AUC values of both aripiprazole and its active metabolite. Use caution when administering ivacaftor and aripiprazole concurrently. Ivacaftor is an inhibitor of CYP3A, and aripiprazole is a CYP3A substrate. Co-administration can increase aripiprazole exposure leading to increased or prolonged therapeutic effects and adverse events. If these agents are used in combination, carefully monitor patients for aripiprazole-related adverse reactions.
    Lurasidone: 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, such as aripiprazole. Therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary.
    Maprotiline: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Maprotiline has 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 torsade de pointes (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. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Aripiprazole should be used cautiously with maprotiline.
    Meclizine: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Mefloquine: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. There is evidence that the use of halofantrine after mefloquine causes a 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. Aripirazole should be used cautiously and with close monitoring with mefloquine.
    Meglitinides: Patients taking meglitinides should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Meperidine; Promethazine: Both promethazine and aripiprazole are associated with a possible risk for QT prolongation; therefore, caution is advisable during coadministration. In addition, because aripiprazole is partially metabolized by CYP2D6, patients should be monitored for aripiprazole-related adverse reactions during concurrent use of a CYP2D6 inhibitor such as promethazine. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP2D6 inhibitor. Coadministration of phenothiazines such as promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Mephobarbital: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Meprobamate: The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including antipsychotics.
    Mesoridazine: Due to the CNS effects of aripiprazole, caution is advisable when aripiprazole is given in combination with centrally-acting medications including other antipsychotics. The risk of drowsiness, dizziness, hypotension, or extrapyramidal symptoms may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary.
    Metaproterenol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Metformin: Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Metformin; Pioglitazone: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. Atypical antipsychotics have been associated with causing hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. In addition, because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as pioglitazone may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in oral aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days.because aripiprazole blood concentrations decline and may become suboptimal. Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Metformin; Repaglinide: Patients taking meglitinides should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Metformin; Rosiglitazone: Aripiprazole has been associated with causing hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when aripiprazole is instituted. Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Metformin; Saxagliptin: Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking saxagliptin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted.The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Metformin; Sitagliptin: Patients taking metformin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. Patients taking sitagliptin should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Methadone: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
    Methamphetamine: Concurrent use of antipsychotics and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
    Methohexital: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Methylphenidate: Methylphenidate is an inhibitor of dopamine reuptake. Pharmacodynamic interactions may occur between methylphenidate and dopamine antagonists such as antipsychotics. Patients receiving methylphenidate in combination with an antipsychotic should be monitored for a decrease in clinical effectiveness of either agent.
    Metoclopramide: 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.
    Metoprolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Metronidazole: 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 with metronidazole include aripiprazole.
    Metyrapone: Because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as metyrapone may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Midazolam: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Mifepristone, RU-486: Because both mifepristone, RU-486 and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4, concurrent use of mifepristone can theoretically lead to an increased risk of aripiprazole-related adverse reactions. In vitro, mifepristone inhibits CYP3A4. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Miglitol: Patients taking alpha-glucosidase inhibitors should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Minoxidil: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Mirabegron: Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as aripiprazole may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
    Mitotane: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when a strong CYP3A4 inducer, such as mitotane, is added to aripiprazole therapy with subsequent adjustments based upon clinical response. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When mitotane is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to the original level over 1 to 2 weeks. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Modafinil: Because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as modafinil may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal
    Molindone: 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), or anticholinergic effects (e.g., constipation, xerostomia) may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
    Monoamine oxidase inhibitors: 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.
    Moxifloxacin: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (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. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval.
    Nabilone: 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.
    Nadolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Nafarelin: Antipsychotics may cause hyperprolactinemia and should not be administered concomitantly with nafarelin since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
    Nalbuphine: 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: Patients taking meglitinides should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Nebivolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Nebivolol; Valsartan: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Nefazodone: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as nefazodone. In adults receiving 300 mg or 400 mg of Abilify Maintena extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. Adults receiving 662 mg or 882 mg of Aristada extended-release injection every 4 weeks should have their Aristada dose reduced to the next lower strength if the CYP3A4 inhibitor is used for more than 14 days. No dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. For patients receiving Aristada 882 mg every 6 weeks, reduce the dose to 441 mg every 4 weeks. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adults receiving Abilify Maintena who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Adults receiving Aristada who are PMs and receiving a strong CYP3A4 inhibitor for more than 14 days should have their Aristada dose reduced from 662 mg or 882 mg to 441 mg; no dosage adjustment is necessary in patients receiving 441 mg of Aristada, if tolerated. For patients receiving Aristada 882 mg every 6 weeks, reduce the dose to 441 mg every 4 weeks. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Avoid use of combination therapy with a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days in patients receiving 662 mg or 882 mg of Aristada; no dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated.
    Nelfinavir: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as nelfinavir. In adults receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Nevirapine: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as nevirapine, is added to aripiprazole therapy with subsequent adjustments based upon clinical response. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Nicardipine: Because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as nicardipine. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Adults receiving 662 mg or 882 mg of Aristada extended-release injection every 4 weeks should have their Aristada dose reduced to the next lower strength if a potent CYP2D6 inhibitor, such as nicardipine, is used for more than 14 days. No dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. For patients receiving Aristada 882 mg every 6 weeks, reduce the dose to 441 mg every 4 weeks. Avoid use of combination therapy with a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days in patients receiving 662 mg or 882 mg of Aristada; no dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated.
    Nifedipine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Nilotinib: Avoid the concomitant use of nilotinib with other agents that prolong the QT interval such as aripiprazole. Additionally, nilotinib is an inhibitor of CYP3A4 and CYP2D6 and aripiprazole is a CYP3A4 and CYP2D6 substrate; administering these drugs together may result in increased aripiprazole levels. If the use of aripiprazole is required, hold nilotinib therapy. If the use of nilotinib and aripiprazole cannot be avoided, dose reduce the oral aripiprazole to one-quarter (25%) of the usual dose. In patients receiving extended-release intramuscular (IM) aripiprazole and nilotinib for more than 14 days, the aripiprazole IM dose should be reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Close monitoring of the QT interval is recommended.
    Nisoldipine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Nitroprusside: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Non-Ionic Contrast Media: Aripiprazole 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: Caution is advised when administering aripiprazole with norfloxacin, as use of these drugs together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Quinolones have also been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Nortriptyline: Combination therapy with aripiprazole and tricyclic antidepressants should be approached with caution and close monitoring. Aripiprazole has a risk for QT prolongation and torsade de pointes, and tricyclics at elevated serum concentrations may produce clinically significant prolongation of the QTc interval. In addition, there is potential for other interactions, such as augmentation of anticholinergic effects.
    Octreotide: Because both octreotide and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4. Octreotide suppresses growth hormone secretion, which may decrease the metabolic clearance of drugs metabolized by CYP3A4. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively
    Ofloxacin: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsades de pointes (TdP). Aripiprazole should be used cautiously and with close monitoring with ofloxacin.
    Olanzapine: Olanzapine is an atypical antipsychotics with a possible risk for QT prolongation and torsade de pointes (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.
    Olodaterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Ombitasvir; Paritaprevir; Ritonavir: Because ritonavir (including lopinavir; ritonavir) and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), these combinations should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as ritonavir. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving the extended-release aripiprazole injection who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Ondansetron: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). Among 42 patients receiving a 4 mg bolus dose of intravenous ondansetron for the treatment of postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after antiemetic administration (p < 0.0001). Risk for QT prolongation increases with increased dosage, and a 32 mg IV dose must no longer be used for prevention of chemotherapy induced emesis. If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended.
    Oritavancin: Aripiprazole is metabolized by CYP3A4 and CYP2D6; oritavancin is a weak CYP3A4 and CYP2D6 inducer. Plasma concentrations and efficacy of aripiprazole may be reduced if these drugs are administered concurrently. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the aripiprazole extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Osimertinib: Osimertinib should be used cautiously and with close monitoring with aripiprazole due to the increased risk of QT prolongation. Aripiprazole is associated with a possible risk for QT prolongation and torsade de pointes (TdP); osimertinib has been associated with concentration-dependent QTc prolongation at the recommended dosing.
    Oxaliplatin: Use caution if coadministration of oxaliplatin with aripiprazole is necessary due to the potential for QT prolongation. Both oxaliplatin and aripiprazole have been assocaited with QT prolongation. Ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in post-marketing experience. If coadministration is necessary, closely monitor for evidence of QT prolongation.
    Oxazepam: Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular (IM) aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly. Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam.
    Oxcarbazepine: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as carbamazepine or oxcarbazepine, is added to aripiprazole therapy. Concurrent use of carbamazepine (200 mg twice daily) and aripiprazole (30 mg/day) resulted in a decrease in Cmax and AUC values of aripiprazole and its active metabolite by about 70%. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Paliperidone: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Paliperidone is an atypical antipsychotic 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.
    Panobinostat: The co-administration of panobinostat with aripiprazole is not recommended; QT prolongation has been reported with both agents. If concomitant use cannot be avoided, closely monitor patients for signs and symptoms of aripiprazole toxicity, including QT prolongation and cardiac arrhythmias. Panobinostat is a CYP2D6 inhibitor and aripiprazole is a CYP2D6 substrate. When a single-dose of a CYP2D6-sensitive substrate was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%).
    Paroxetine: Paroxetine, a potent inhibitor of CYP2D6, may decrease the metabolism of CYP2D6 substrates such as aripiprazole. Decreased metabolism of aripiprazole may lead to adverse effects such as extrapyramidal symptoms. In addition, aripiprazole has been associated with QT prolongation, and concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such an event. The manufacturer of aripiprazole recommends that the oral aripiprazole dose be reduced by one-half when coadministered with CYP2D6 inhibitors. In adult patients receiving 300 mg or 400 mg of the extended-release injection, dose reductions to 200 mg or 300 mg, respectively, are recommended if a potent CYP2D6 inhibitor is used for more than 14 days. It should be noted that aripiprazole dosage adjustments are not required when it is added as adjunctive treatment to antidepressants for major depressive disorder, if the manufacturer's dosing guidelines for this indication are followed. Currently available data indicate no clinically significant pharmacokinetic changes to paroxetine with coadministration.
    Pasireotide: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Cautious use of pasireotide and drugs that prolong the QT interval is needed, as coadministration may have additive effects on the prolongation of the QT interval.
    Pazopanib: Because both pazopanib and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and aripiprazole, a CYP3A4 substrate, may cause an increase in systemic concentrations of aripiprazole. Use caution when administering these drugs concomitantly.
    Peginterferon Alfa-2b: Monitor for adverse effects associated with increased exposure to aripiprazole if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while aripiprazole is a CYP2D6 substrate.
    Penbutolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Pentamidine: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Systemic pentamidine has been associated with QT prolongation. Aripiprazole should be used cautiously and with close monitoring with pentamidine.
    Pentazocine: Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with atypical antipsycotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
    Pentazocine; Naloxone: Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with atypical antipsycotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
    Pentobarbital: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Pergolide: Pergolide is a potent dopamine-receptor agonist. Antipsychotic agents may inhibit the clinical antiparkinsonian response to pergolide by blocking dopamine receptors in the brain. In general, the atypical antipsychotics are less likely to interfere with antiparkinsons treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to pergolide.
    Perindopril; Amlodipine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Perphenazine: Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongatio, such as aripiprazole. Additionally, increased aripiprazole blood levels are expected when it is coadministered with inhibitors of CYP2D6, such as perphenazine. A dosage adjustment of aripiprazole is necessary when these drugs are used concomitantly, and conversely, when perphenazine is discontinued in a patient taking aripiprazole. Co-administration of perphenazine with atypical agents 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.
    Perphenazine; Amitriptyline: Combination therapy with aripiprazole and tricyclic antidepressants should be approached with caution and close monitoring. Aripiprazole has a risk for QT prolongation and torsade de pointes, and tricyclics at elevated serum concentrations may produce clinically significant prolongation of the QTc interval. In addition, there is potential for other interactions, such as augmentation of anticholinergic effects. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongatio, such as aripiprazole. Additionally, increased aripiprazole blood levels are expected when it is coadministered with inhibitors of CYP2D6, such as perphenazine. A dosage adjustment of aripiprazole is necessary when these drugs are used concomitantly, and conversely, when perphenazine is discontinued in a patient taking aripiprazole. Co-administration of perphenazine with atypical agents 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.
    Phenelzine: 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: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Phenoxybenzamine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Phentermine; Topiramate: Because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as topiramate may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Phentolamine: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Phenylephrine; Promethazine: Both promethazine and aripiprazole are associated with a possible risk for QT prolongation; therefore, caution is advisable during coadministration. In addition, because aripiprazole is partially metabolized by CYP2D6, patients should be monitored for aripiprazole-related adverse reactions during concurrent use of a CYP2D6 inhibitor such as promethazine. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP2D6 inhibitor. Coadministration of phenothiazines such as promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Phenytoin: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled when a potential CYP3A4 inducer, such as ethotoin, phenytoin, or fosphenytoin, is added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced to 10 mg to 15 mg. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal.
    Pimavanserin: Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as aripiprazole. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Coadministration may increase the risk for QT prolongation.
    Pimozide: QT prolongation occurred during therapeutic use of aripiprazole and following overdose. Because pimozide has an established risk of QT prolongation and torsade de pointes (TdP), pimozide is contraindicated for use with aripiprazole.
    Pindolol: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Pioglitazone: Patients taking antidiabetic agents should be closely monitored for worsening glycemic control when any of these antipsychotics is instituted. Atypical antipsychotics have been associated with causing hyperglycemia, even diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported. In addition, because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as pioglitazone may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in oral aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of the extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days.because aripiprazole blood concentrations decline and may become suboptimal.
    Pirbuterol: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Caution advised if administering with other drugs that may cause QT prolongation and torsade de pointes (TdP), including beta-agonists.
    Posaconazole: Concurrent use of aripiprazole and posaconazole is contraindicated due to the possible risk of QT prolongation and torsade de pointes (TdP) with each agent and the potential for posaconazole to increase plasma concentrations of aripiprazole through inhibition of CYP3A4, one of the metabolic pathways of aripiprazole.
    Potassium-sparing diuretics: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Pramipexole: Pramipexole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of pramipexole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Pramlintide: Patients taking pramlintide should be closely monitored for worsening glycemic control when atypical antipsychotics are instituted. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. While a causal relationship has not been established, temporal associations of atypical antipsychotic therapy with the aggravation of diabetes mellitus have been reported.
    Prazosin: Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Primaquine: 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 aripiprazole.
    Primidone: Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as primidone or other barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of the Abilify Maintena extended-release intramuscular injection with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg or 882 mg of Aristada extended-release injection and receiving a strong CYP3A4 inducer for more than 14 days, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg.
    Procainamide: QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes. Aripiprazole should be used cautiously and with close monitoring with procainamide.
    Prochlorperazine: Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Prochlorperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as aripiprazole. Co-administration of prochlorperazine 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.
    Promethazine: Both promethazine and aripiprazole are associated with a possible risk for QT prolongation; therefore, caution is advisable during coadministration. In addition, because aripiprazole is partially metabolized by CYP2D6, patients should be monitored for aripiprazole-related adverse reactions during concurrent use of a CYP2D6 inhibitor such as promethazine. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP2D6 inhibitor. Coadministration of phenothiazines such as promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
    Propafenone: Because both propafenone and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to at least one-half of the usual dose in patients receiving potential inhibitors of CYP2D6, such as propafenone; exceptions include those patients receiving adjunct aripiprazole for major depressive disorder for whom no dosage adjustment is recommended. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their extended-release intramuscular dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively.
    Propranolol: Aripiprazole may