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  • CLASSES

    Antidepressant Augmentation Agents
    Partial Dopamine Receptor Agonist Antipsychotics

    BOXED WARNING

    Children, suicidal ideation

    Safety and efficacy of oral aripiprazole has been demonstrated in pediatric patients 6 years of age or older for selected indications. Injectable formulations of aripiprazole are not approved for those less than 18 years of age for any indication. Because oral aripiprazole is approved for the adjunct treatment of major depression in adults, a boxed warning in the product label describes the risk of suicidality and suicidal ideation in children, adolescent, and young adult patients receiving antidepressants. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in adults and pediatric individuals 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. Weigh the need for an antidepressant in children, adolescents, or young adults  against the risk of suicidality; it is unknown if this risk extends to adjunctive treatment or long-term use. Monitor all patients for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of aripiprazole may be necessary in patients with emerging suicidality or worsening depression.

    Dementia, geriatric, stroke

    Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients; avoid use of aripiprazole if possible due to an increase in morbidity and mortality in elderly patients with dementia receiving antipsychotics. Deaths have typically resulted from heart failure, sudden death, or infections (primarily pneumonia). An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. A low starting dose is recommended for the older adult patient if aripiprazole is used. The Beers Criteria consider antipsychotics to be potentially inappropriate medications (PIMs) in elderly patients except for treating schizophrenia, bipolar disorder, and nausea/vomiting during chemotherapy. The Beers panel recommends avoiding antipsychotics in geriatric patients with delirium, dementia, or Parkinson's disease. Non-pharmacological strategies are first-line options for treating delirium- or dementia-related behavioral problems unless they have failed or are not possible and the patient is a substantial threat to self or others. If antipsychotic use is necessary in geriatrics with a history of falls or fractures, consider reducing the use of other CNS depressants and implement other fall risk strategies. Due to the potential for antipsychotic-induced hyponatremia and SIADH, sodium levels should be closely monitored when aripiprazole is initiated and after dose changes. According to the federal Omnibus Budget Reconciliation Act (OBRA) regulations in residents of long-term care facilities, antipsychotic therapy should only be initiated in a patient with behavioral or psychological symptoms of dementia (BPSD) when the patient is a danger to self or others or has symptoms due to mania or psychosis. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Antipsychotics are subject to periodic review for effectiveness, medical necessity, gradual dose reduction (GDR), or rationale for continued use. Refer to the OBRA guidelines for complete information.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral atypical antipsychotic of the dopamine system stabilizers class
    Used orally in adults for schizophrenia, bipolar I disorder, and as an adjunct for major depression; short-acting injection used for agitation; distinct extended-release IM injections are used for maintenance of selected indications; used orally in pediatric patients for schizophrenia, bipolar I disorder, Tourette's syndrome, or irritability due to autism
    Boxed warning related to an increased risk of suicidality in children, adolescents, and young adults, as well as regarding increased mortality risk in elderly patients treated for dementia-related psychosis

    COMMON BRAND NAMES

    Abilify, Abilify Asimtufii, Abilify Discmelt, Abilify Maintena, Abilify Mycite, Aristada

    HOW SUPPLIED

    Abilify Asimtufii/Aristada Intramuscular Inj Susp ER: 1.6mL, 2.4mL, 3.2mL, 3.9mL, 441mg, 662mg, 675mg, 720mg, 882mg, 960mg, 1064mg
    Abilify Discmelt/Aripiprazole Oral Tab Orally Dis: 10mg, 15mg
    Abilify Maintena Intramuscular Inj Pwd F/Susp ER: 300mg, 400mg
    Abilify/Abilify Mycite/Aripiprazole Oral Tab: 2mg, 5mg, 10mg, 15mg, 20mg, 30mg
    Abilify/Aripiprazole Oral Sol: 1mg, 1mL

    DOSAGE & INDICATIONS

    For the treatment of schizophrenia.
    Oral dosage (immediate-release oral dosage forms, tablets, orally disentegrating tablets, oral solution)
    Adults

    10 to 15 mg PO once daily is the starting and suggested target dosage. Titrate no more frequently than every 2 weeks. Max: 30 mg/day, but doses greater than 15 mg/day have not shown meaningful increased benefit. ORAL SOLUTION DOSING: Substitute 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 CYP2D6 poor metabolizers (CYP2D6 PMs), reduce to one-half of the usual dose, then titrate to clinical response. In CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase back to the original 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.

    Adolescents

    2 mg PO once daily, initially. Increase to 5 mg PO once daily after 2 day, then after 2 more days increase to the target dose of 10 mg PO once daily. May titrate in 5 mg increments, usually every 2 weeks to assess effectiveness and tolerability. Max: 30 mg/day PO, but increased benefit beyond 10 mg/day has not been demonstrated. ORAL SOLUTION DOSING: Substitute 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 CYP2D6 poor metabolizers (CYP2D6 PMs), reduce to one-half of the usual dose, then adjust to clinical response. In CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase back to the original dose.

    Oral dosage (aripiprazole tablet with sensor, Abilify Mycite)
    Adults

    10 to 15 mg PO once daily is the starting and suggested target dosage. Titrate no more frequently than every 2 weeks. Max: 30 mg/day, but doses greater than 15 mg/day have not shown meaningful increased benefit. The use of Abilify Mycite to track drug ingestion in "real-time" or during an emergent event is not recommended because detection may be delayed or not occur. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In CYP2D6 poor metabolizers (CYP2D6 PMs), reduce to one-half of the usual dose, then titrate to clinical response. In CYP2D6 PMs receiving a strong CYP3A4 inhibitor, reduce to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase back to the original 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.

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

    Establish tolerability with oral aripiprazole prior to initiating Abilify Maintena. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.

    Adults

    Abilify Maintena 400 mg IM once monthly, give maintenance doses no sooner than 26 days after the previous injection. At initiation, oral aripiprazole (10 to 20 mg per day) or other oral antipsychotic should be continued for 14 consecutive days to maintain therapeutic concentrations. 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 CYP2D6 poor metabolizers (CYP2D6 PMs), the recommended starting and maintenance dose is Abilify Maintena 300 mg IM once monthly. In CYP2D6 PMs receiving a CYP3A4 inhibitor for more than 14 days, reduce to 200 mg IM once monthly. 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 (every 2-month extended-release injectable suspension; i.e., Abilify Asimtufii)

    NOTE: Establish tolerability with oral aripiprazole prior to initiating Abilify Asimtufii. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability. 

    Adults

    Abilify Asimtufii 960 mg IM once every 2 months (56 days after previous injection). If needed, maintenance doses may be given up to 2 weeks before or 2 weeks after the 2-month scheduled time point. If there are adverse reactions to the 960 mg dosage, may decrease to 720 mg IM once every 2 months. INITIATION: When initiating in patients receiving oral aripiprazole or other oral antipsychotic, administer the first dose of Abilify Asimtufii and continue oral aripiprazole (10 to 20 mg per day) or the other oral antipsychotic for 14 consecutive days to maintain therapeutic concentrations. CONVERSION FROM ABILIFY MAINTENA EXTENDED RELEASE INJECTION: For patients receiving Abilify Maintena, administer Abilify Asimtufii in place of the next scheduled injection of Abilify Maintena. The first Abilify Asimtufii injection may be administered in place of the second or later injection of Abilify Maintena. ADJUSTMENTS: Coadministration of certain medications may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients who are taking 960 mg of Abilify Asimtufii and require a strong CYP2D6 or strong CYP3A4 inhibitor for more than 14 days should receive a reduced dose of 720 mg IM once every 2 months. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), the recommended dose is Abilify Asimtufii 720 mg IM once every 2 months. CYP2D6 PMs who are receiving a CYP3A4 inhibitor for more than 14 days should not use Abilify Asimtufii. MISSED DOSES: If more than 8 weeks and less than 14 weeks have elapsed since the last injection, administer the next dose of Abilify Asimtufii as soon as possible and resume the once every 2 month schedule. If more than 14 weeks have elapsed since the last injection, restart concomitant oral aripiprazole for 14 days with the next administered injection of Abilify Asimtufii.

    Intramuscular dosage (extended-release aripiprazole lauroxil injectable suspension; i.e., Aristada)

    NOTE: In aripiprazole-naive patients, establish tolerability with oral aripiprazole prior to initiating treatment with Aristada. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.

    Adults 18 to 65 years of age

    May initiate Aristada 441 mg, 662 mg, or 882 mg IM monthly, 882 mg IM every 6 weeks, or 1,064 mg IM every 2 months, according to individual needs of the patient. May adjust dosage and interval as needed, taking into account the pharmacokinetics and prolonged-release characteristics of Aristada. If early dosing is needed to accommodate the patient's schedule, do not give earlier than 14 days after the previous injection. THERE ARE TWO OPTIONS FOR INITIATING TREATMENT WITH ARISTADA. INITIATION OPTION ONE: Administer Aristada Initio 675 mg IM single dose and aripiprazole 30 mg PO single-dose in conjunction with the first Aristada injection. May give Aristada and Aristada Initio on the same day or up to 10 days thereafter; avoid injecting concurrently into the same muscle. INITIATION OPTION TWO: Continue oral aripiprazole for 21 consecutive days in conjunction with the first Aristada injection. SUGGESTED ARISTADA DOSAGE SELECTION FOR PATIENTS STABILIZED ON ORAL ARIPIPRAZOLE: 10 mg/day PO (Aristada 441 mg/month IM); 15 mg/day PO (Aristada 662 mg/month IM, 882 mg IM every 6 weeks, or 1,064 mg IM every 2 months); and 20 mg/day or higher PO (Aristada 882 mg/month IM). CONVERSION FROM ABILIFY MAINTENA EXTENDED-RELEASE IM INJECTION: Abilify Maintena doses of 300 mg, 450 mg, 600 mg, and 724 mg correspond to 441 mg, 662 mg, 882 mg, and 1,064 mg respectively, of Aristada. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In CYP2D6 poor metabolizers who are receiving a strong CYP3A4 inhibitor for more than 2 weeks, reduce the Aristada dose to 441 mg/month from 662 mg/month, 882 mg every month to 6 weeks, or 1,064 mg every 2 months. No dosage adjustment is needed for the 441 mg/month dose of Aristada, if tolerated. 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 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 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. 3) For patients who miss a dose while receiving 1,064 mg IM every 2 months: If it has been 10 weeks or less since the missed dose, no oral supplementation is required. If it has been more than 10 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 as when the patient began Aristada.

    Intramuscular dosage (extended-release aripiprazole lauroxil injection for single dose use; e.g., Aristada Initio ONLY)

    NOTE: Aristada Initio is used as a single dose as part of an initiation regimen for Aristada, and is not interchangeable with Aristada due to differing pharmacokinetics.

    Adults 18 to 65 years of age

    Aristada Initio 675 mg IM as a single dose given with aripiprazole 30 mg PO single dose - these are given in conjunction with the first Aristada IM injection (at a different site) or up to 10 days thereafter. (Aristada Initio may also be used as a single dose to re-initiate Aristada following a missed dose of Aristada). Avoid use in CYP2D6 poor metabolizers. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the acute treatment of mania and mixed episodes and maintenance treatment of bipolar disorder (Bipolar I Disorder).
    Oral dosage (immediate-release oral dosage forms, tablets, orally disentegrating tablets, oral solution)
    Adults

    INITIAL MONOTHERAPY DOSING FOR ACUTE OR MAINTENANCE TREATMENT: 15 mg/day PO. INITIAL DOSING FOR ACUTE OR MAINTENANCE TREATMENT AS ADJUNCT THERAPY TO LITHIUM OR VALPROATE: 10 to 15 mg/day PO. The recommended target dose as monotherapy or adjunct therapy to lithium or valproate is 15 mg/day. May titrate if needed/tolerated. Use the lowest effective dose. Max: 30 mg/day PO. Maintenance studies with aripiprazole as monotherapy or adjunct therapy showed a significant delay in relapse to manic episodes, but not depressive episodes, compared to placebo. ORAL SOLUTION DOSING: Substitute 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 CYP2D6 poor metabolizers (CYP2D6 PMs), reduce to one-half of the usual dose, then adjust to clinical response. In CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase back to the original dose.

    Children and Adolescents 10 years and older

    ACUTE OR MAINTENANCE THERAPY: 2 mg PO once daily, initially. After 2 days, titrate to 5 mg once daily, and then titrate to a target dose of 10 mg/day after an additional 2 days. Subsequent increases should occur in increments of 5 mg/day. Use lowest effective dose. Max: 30 mg/day PO. ORAL SOLUTION DOSING: Substitute 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 CYP2D6 poor metabolizers (CYP2D6 PMs), reduce to one-half of the usual dose, then adjust to clinical response. In CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase back to the original dose.

    Oral dosage (oral tablet with sensor; e.g., Abilify Mycite)
    Adults

    INITIAL MONOTHERAPY DOSE FOR ACUTE OR MAINTENANCE THERAPY: 15 mg/day PO. INITIAL DOSE FOR ACUTE OR MAINTENANCE TREATMENT AS ADJUNCT TREATMENT TO LITHIUM OR VALPROATE: 10 to 15 mg/day PO. The recommended target dose as monotherapy or adjunct therapy to lithium or valproate is 15 mg/day. May titrate if needed/tolerated. Use lowest effective dose. Max: 30 mg/day PO. Maintenance studies with aripiprazole as monotherapy or adjunct therapy showed a significant delay in relapse to manic episodes, but not depressive episodes, compared to placebo. The use of Abilify Mycite to track drug ingestion in "real-time" or during an emergent event is not recommended because detection may be delayed or not occur. ORAL SOLUTION DOSING: Substitute 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 CYP2D6 poor metabolizers (CYP2D6 PMs), reduce to one-half of the usual dose, then adjust to clinical response. In CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase back to the original dose.

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

    FOR MAINTENANCE TREATMENT: The initial and maintenance dose is 400 mg IM once monthly; give maintenance doses no sooner than 26 days after the previous injection. At initiation, oral aripiprazole (10 to 20 mg per day) or other oral antipsychotic should be continued for 14 consecutive days to maintain therapeutic concentrations. Once stabilized, may reduce to 300 mg IM once monthly if needed. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In CYP2D6 poor metabolizers (CYP2D6 PMs), the recommended starting and maintenance dose is Abilify Maintena is 300 mg IM once monthly. In CYP2D6 PMs receiving a CYP3A4 inhibitor for more than 14 days, reduce to 200 mg IM once monthly. 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 (once every 2-month extended-release intramuscular suspension; i.e., Abilify Asimtufii)
    Adults

    FOR MAINTENANCE TREATMENT: Abilify Asimtufii 960 mg IM once every 2 months (56 days after previous injection). If needed, maintenance doses may be given up to 2 weeks before or 2 weeks after the 2-month scheduled time point. If there are adverse reactions to the 960 mg dosage, may decrease to 720 mg IM once every 2 months. INITIATION: When initiating in patients receiving oral aripiprazole or other oral antipsychotic, administer the first dose of Abilify Asimtufii and continue oral aripiprazole (10 to 20 mg per day) or the other oral antipsychotic for 14 consecutive days to maintain therapeutic concentrations. CONVERSION FROM ABILIFY MAINTENA EXTENDED RELEASE INJECTION: For patients receiving Abilify Maintena, administer Abilify Asimtufii in place of the next scheduled injection of Abilify Maintena. The first Abilify Asimtufii injection may be administered in place of the second or later injection of Abilify Maintena. ADJUSTMENTS: Coadministration of certain medications may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients who are taking 960 mg of Abilify Asimtufii and require a strong CYP2D6 or strong CYP3A4 inhibitor for more than 14 days should receive a reduced dose of 720 mg IM once every 2 months. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), the recommended dose is Abilify Asimtufii 720 mg IM once every 2 months. CYP2D6 PMs who are receiving a CYP3A4 inhibitor for more than 14 days should not use Abilify Asimtufii. MISSED DOSES: If more than 8 weeks and less than 14 weeks have elapsed since the last injection, administer the next dose of Abilify Asimtufii as soon as possible and resume the once every 2 month schedule. If more than 14 weeks have elapsed since the last injection, restart concomitant oral aripiprazole for 14 days with the next administered injection of Abilify Asimtufii.

    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 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. It should be noted that the use of Abilify Mycite (aripiprazole tablets with sensor) to track drug ingestion in "real-time" or during an emergent event is not recommended because detection may be delayed or not occur. 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 or chronic tic disorders†.
    NOTE: The FDA has designated aripiprazole as an orphan drug for this indication.
    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. 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. Max: 20 mg/day PO. 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. Max: 10 mg/day PO. In all patients, 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 CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust to favorable clinical response. In 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). The American Academy of Neurology states that aripiprazole is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; however, there is insufficient evidence to determine the efficacy of aripiprazole relative to other antipsychotics used to treat tics.

    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); 960 mg every 2 months extended-release IM (Abilify Asimtufii); 882 mg/month extended-release IM (Aristada); 675 mg IM single-dose administration (Aristada Initio).

    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); 960 mg every 2 months extended-release IM (Abilify Asimtufii); 882 mg/month extended-release IM (Aristada); 675 mg IM single-dose administration (Aristada Initio), but safety and efficacy of Aristada and Aristada Initio have not established in geriatric adults older than 65 years of age.

    Adolescents

    Weighing 50 kg or more: 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, Abilify Asimtufii, Aristada, Aristada Initio) have not been established.
    Weighing 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, Abilify Asimtufii, Aristada, Aristada Initio) have not been established.

    Children

    10 to 12 years and weighing 50 kg or more: 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.
    10 to 12 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 to 9 years and weighing 50 kg or more: 15 mg/day PO for autism; 20 mg/day PO for Tourette's syndrome; not indicated for bipolar disorder or schizophrenia.
    6 to 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.
    Less than 6 years: Safety and efficacy have not been established.

    Infants

    Not indicated.

    Neonates

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment for oral or parenteral aripiprazole is required on the basis of a patient's hepatic function (mild to severe hepatic impairment, Child-Pugh score between 5 and 15).

    Renal Impairment

    No dosage adjustment for oral or parenteral aripiprazole is required on the basis of a patient's renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 mL/minute).
     
    Intermittent hemodialysis
    Hemodialysis is unlikely to be effective in removing aripiprazole since the drug is highly bound to plasma proteins.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Oral immediate release tablets (e.g., Abilify):
    May be administered without regard to meals.
     
    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.
    Place the tablet on the tongue and allow to dissolve. Tablet disintegration occurs rapidly in saliva.
    Do not take with liquid unless it is necessary to do so. Do not divide the tablets in half.
    May be administered without regard to meals.
     
    Oral tablets with sensor (e.g., Abilify Mycite):
    General instructions:
    Prior to patient use, the healthcare provider should facilitate the use of the product and its components (patch, application, portal) and ensure the patient is capable and willing to use smartphones and apps.
    Before using any component of the system, instruct patients to download the Mycite app and follow all of the instructions for use and ensure that the app is compatible with the specific smartphone of the patient.
    The system includes a web-based portal for healthcare providers and caregivers.
    Advise patients that if their smartphone is lost, impaired, or disabled, some information collected by the system may be lost. If the patient's device is lost or disabled, the Mycite patch should be changed immediately and connected to a new mobile device using their current account information. Information previously synced to the patient's account will be available.
    Mycite tablets:
    May administer without regard to meals.
    Swallow tablets whole; do not divide, crush, or chew.
    The tablets are embedded with an Ingestible Event Marker (IEM) intended to track drug ingestion in conjunction with a wearable sensor (Mycite patch) and smartphone app.
    Although most ingestion will be detected within 30 minutes, it may take up to two hours for the smartphone app and web portal to detect ingestion of the tablet. If the tablet is not detected after ingestion, do not repeat the dose.
    It is not recommended to use the tablets to track drug ingestion in "real-time" or during an emergency because detection may be delayed or not occur.
    Mycite patch:
    The patch detects the signal from the IEM sensor embedded in the tablet after ingestion and transmits data to a smartphone.
    Apply only when instructed by the Mycite smartphone application (Mycite app) to the left side of the body just above the lower edge of the rib cage.
    Ensure that the app is paired with the patch prior to use. The status of the patch is indicated by a status icon in the app to inform the user that the patch is properly adhered and fully functioning.
    Do not place the patch where the skin is scraped, cracked, inflamed, or irritated, or in an area that overlaps the most recently removed patch.
    Do not remove the patch when showering, swimming, or exercising.
    Change the patch weekly or sooner if needed. The app will prompt you to change the patch and will direct you to apply and remove the patch correctly.
    Remove the patch when having an MRI and replace it with a new one as soon as possible. If there is skin irritation, remove the patch.

    Oral Liquid Formulations

    Oral solution:
    Administer using a calibrated oral measuring device.
    May be administered without regard to meals.
    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 (IM) use only. Do not administer intravenously or subcutaneously.
    Available as a ready-to-use injectable solution.
    Inject slowly and deeply into muscle mass.
    Wait at least 2 hours between doses.
    Discard any unused portion.
     
    Extended-release intramuscular injection (i.e., Abilify Maintena) Single-Use Vial Preparation, Reconstitution, and Administration:
    -Preparation of adapter-syringe assembly:
    For intramuscular (IM) use only. Do not administer intravenously or subcutaneously.
    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 and Dose preparation 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.
    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. 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 once prepared from Vial:
    For once-monthly deep intramuscular gluteal or deltoid injection by a health care 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.
    Refer to the Administration Instructions section of the official product labeling for detailed visual aids which accompany the written instructions.
     
    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 health care 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. Immediately discard the used syringe and unused needle in an approved sharps container. The unused needle should not be saved for future use.
    For subsequent injections, rotate sites of injection between the two gluteal or deltoid muscles.
    Refer to the Administration Instructions section of the official product labeling for detailed visual aids which accompany the written instructions.
     
    Extended-release aripiprazole lauroxil intramuscular injection (i.e., Aristada)
    -General Administration Guidelines:
    For administration as a long-acting intramuscular injection by a health care professional. Do not administer by any other route.
    Prior to administering Aristada, establish tolerability with oral aripiprazole in patients who have never taken aripiprazole. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
    The 441 mg dose may be administered in the deltoid or gluteal muscle, whereas all other doses (662 mg, 882 mg, and 1,064 mg) should be administered in the gluteal muscle.
    When initiating Aristada in conjunction with a single dose of Aristada Initio 675 mg, avoid injecting both Aristada Initio and Aristada concurrently into the same deltoid or gluteal muscle.
    The dose and dosing interval may be adjusted, taking into account the pharmacokinetics and prolonged-release characteristics of Aristada.
    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 scheduled dose, refer to the dosing and administration recommendations for patients which are determined by the length of time since the last injection.
    -Extended-release aripiprazole lauroxil injection (i.e., Aristada) 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, 1.5-inch), or Gluteal (20 gauge, 1.5-inch or 20 gauge, 2-inch).
    662 mg dose: Gluteal (20 gauge, 1.5-inch or 20 gauge, 2-inch).
    882 mg dose: Gluteal (20 gauge, 1.5-inch or 20 gauge, 2-inch).
    1,064 mg dose: Gluteal (20 gauge, 1.5-inch or 20 gauge, 2-inch).
    Attach the injection needle to the syringe securely with a clockwise twisting motion. Do not over-tighten, 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 contents of the syringe IM. 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. Immediately discard the used syringe and unused needle in an approved sharps container. The unused needles should not be saved for future use.
    Refer to the Administration Instructions section of the official product labeling for detailed visual aids which accompany the written instructions.
     
    Single-dose extended-release aripiprazole lauroxil intramuscular injection (i.e., Aristada Initio) Pre-filled Syringe Preparation, Administration, and Disposal:
    Aristada Initio is not interchangeable with Aristada due to differing pharmacokinetics.
    For use as a single intramuscular dose in the deltoid or gluteal muscle in patients initiating Aristada or after a missed dose of Aristada. Do not inject by any other route.
    The kit contains a syringe with a sterile suspension of 675 mg/2.4 mL of Aristada Initio and 3 safety needles (a 2-inch 20 gauge needle with yellow needle hub, a 1.5-inch 20 gauge needle with yellow needle hub, and a 1-inch 21 gauge needle with a green needle hub).
    This product should only be administered by a health care professional.
    Avoid injecting Aristada Initio and Aristada concurrently into the same deltoid or gluteal muscle.
    Tap the syringe at least 10 times to dislodge any settled material and vigorously shake the syringe for at least 30 seconds to ensure a uniform suspension.
    If the syringe is not used within 15 minutes, shake again for 30 seconds.
    Select needle size based on injection site. For patients with a larger amount of subcutaneous tissue overlaying the injection site muscle, use the longer of the needles provided.
    Deltoid: 21 gauge, 1-inch or 20 gauge, 1.5-inch.
    Gluteal: 20 gauge 1.5-inch or 20 gauge, 2-inch.
    Attach the injection needle to the syringe securely with a clockwise twisting motion. Do not overtighten, since this could lead to needle hub cracking.
    Prime the syringe to remove air by bringing syringe into upright position and tapping, then depress the plunger rod to remove air until a few drops are released. Small air bubbles in the syringe are normal.
    Inject IM in a rapid and continuous manner. Product requires a rapid injection; do not hesitate.
    Cover the needle by pressing the safety device. Immediately discard the used syringe and unused needle in an approved sharps container. The unused needle should not be saved for future use.
    Refer to the Administration Instructions section of the official product labeling for detailed visual aids which accompany the written instructions.
     
    Extended-release intramuscular injection (i.e., Abilify Asimtufii) Pre-Filled Syringe Preparation, Administration, and Disposal:
    To be prepared and administered by a health care professional only.
    For use as a single intramuscular dose every 2-months by gluteal IM injection only. Do not administer by any other route.
    Prior to administration, ensure suspension is a uniform, homogenous suspension that is opaque and milky-white in color. Do not use if suspension is discolored or particulate matter is present
    Remove Abilify Asimtufii pre-filled syringe from the package.
    Tap the syringe on your hand at least 10 times, then shake the syringe vigorously for at least 10 seconds until the medication is uniform.
    Select needle size based on patient body type.
    For non-obese patients: 22-gauge, 1.5-inch safety needle with needle protection device (needle in black packaging)
    For obese patients: 21-gauge, 2-inch safety needle with needle protection device (needle in green packaging)
    Twist and pull off the pre-filled syringe tip-cap. While holding the base of the needle, ensure the needle is firmly seated on the safety device with a push. Gently twist clockwise until securely fitted.
    When ready to administer the injection, hold the pre-filled syringe upright and remove the needle-cap straight up. Do not twist the needle-cap, as this may loosen the needle from the syringe.
    Slowly advance the plunger rod upward to expel the air and until the suspension fills the needle base.
    Slowly inject the entire contents of the pre-filled syringe IM into the gluteal muscle. Do not administer by any other route. Do not massage the injection site.
    After the injection, press the safety shield on a hard surface to cover and lock the shield over the needle.
    Immediately discard the used syringe and unused needle in an approved sharps container. The unused needle should not be saved for future use.

    STORAGE

    Abilify:
    - Discard unused product 6 months after opening the bottle
    - Protect from moisture
    - Store at 20 to 25 degrees C (68 to 77 degrees F); excursions permitted between 15 to 30 degrees C (59 to 86 degrees F) USP Controlled Room Temperature
    Abilify Asimtufii:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Abilify Discmelt:
    - Protect from heat
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a dry, well ventilated place
    Abilify Maintena:
    - Discard unused portion. Do not store for later use.
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Abilify Mycite:
    - Do not store in conditions where tablets are exposed to humid conditions
    - Store between 5 to 27 degrees C (41 to 81 degrees F), 15% to 93% relative humidity
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Aristada:
    - Do not freeze
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Cerebrovascular disease, seizure disorder, seizures

    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. In clinical trials with oral aripiprazole, seizures occurred in a few adult (0.1%) and pediatric (0.3%) patients. In addition, seizures occurred in 0.2% of patients receiving intramuscular aripiprazole during clinical trials.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypotension, hypothermia, hypothyroidism, hypovolemia, long QT syndrome, myocardial infarction, orthostatic hypotension, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, syncope, systemic lupus erythematosus (SLE)

    Aripiprazole can cause orthostatic hypotension associated with dizziness and, in rare cases, syncope; use caution 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 and reassessed as needed in patients with conditions, diseases, or concurrent medication use that could exacerbate orthostasis. In rare instances, QT prolongation has been reported during therapeutic use of aripiprazole and following overdose, which may present a possible risk for torsade de pointes (TdP). Use aripiprazole with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, cerebrovascular accident, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, those 65 years of age and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    Agranulocytosis, hematological disease, leukopenia, neutropenia

    Use aripiprazole with caution in those 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. Consider discontinuation of the antipsychotic if a clinically significant decline in WBC occurs in the absence of an identifiable cause. Monitor patients with clinically significant neutropenia closely for fever and infection; institute appropriate medical intervention if necessary. Aripiprazole should be discontinued in patients with severe neutropenia (absolute neutrophil count less than 1,000/mm3), with ongoing medical care until the symptoms resolve.

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

    Somnolence/drowsiness is a commonly reported adverse effect of aripiprazole. Somnolence from antipsychotic use could lead to falls with the potential for fractures and other injuries. Complete a fall risk assessment when initiating an antipsychotic in those with conditions, diseases, or use of concurrent medication that may exacerbate CNS effects and reassess as needed with continued treatment. Aripiprazole may have the potential to impair judgment, thinking, or motor skills, so advise patients about driving or operating machinery or other hazardous tasks until they are reasonably certain that aripiprazole does not affect them adversely. Given the primary CNS effects of aripiprazole, use caution 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 use has been associated with esophageal dysmotility and aspiration of gastric contents, which may increase the incidence of aspiration pneumonia in certain populations, such as those with advanced Alzheimer's disease.

    Children, suicidal ideation

    Safety and efficacy of oral aripiprazole has been demonstrated in pediatric patients 6 years of age or older for selected indications. Injectable formulations of aripiprazole are not approved for those less than 18 years of age for any indication. Because oral aripiprazole is approved for the adjunct treatment of major depression in adults, a boxed warning in the product label describes the risk of suicidality and suicidal ideation in children, adolescent, and young adult patients receiving antidepressants. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in adults and pediatric individuals 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. Weigh the need for an antidepressant in children, adolescents, or young adults  against the risk of suicidality; it is unknown if this risk extends to adjunctive treatment or long-term use. Monitor all patients for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of aripiprazole may be necessary in patients with emerging suicidality or worsening depression.

    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 medication is discontinued or the dose is reduced. Inform patients and caregivers of the risk of impulse control symptoms. Because patients may not recognize these behavioral changes as abnormal, health care providers should specifically ask patients about any new or increasing urges or compulsions during aripiprazole treatment. 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). Impulse control symptoms can also be associated with the underlying disorder. Consider a reduction in dose or discontinuation of the medication 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 medications 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. Monitor for symptoms of hyperglycemia (e.g., polydipsia, polyuria, polyphagia, weakness). Regularly monitor patients with established diabetes mellitus for worsening of glucose control during atypical antipsychotic treatment. In those with risk factors for diabetes mellitus (e.g., obese patients, family history of diabetes), perform fasting blood glucose testing at the beginning of treatment. In patients who develop symptoms of hyperglycemia during treatment, order 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. Consider dosage formulation specific factors; each mL of aripiprazole oral solution contains 400 mg of sucrose and 200 mg of fructose that may need to be considered in patients with known hyperglycemia.

    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 medications 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 in those with pre-existing risk factors, such as diabetes, obesity, or hyperlipidemia (e.g., hypercholesterolemia or hypertriglyceridemia). Inform all patients of the importance of maintaining a nutritionally balanced diet during treatment. 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

    Tardive dyskinesia (TD) is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotics. Regular evaluation for movement disorders is recommended (e.g., AIMS, DISCUS). Factors associated with a greater susceptibility to TD include an age above 55 years, female gender, white or African ethnicity, presence of a mood disorder, intellectual disability, CNS injury, prior or current akathisia, significant parkinsonism, or acute dystonic reaction. The rate of TD in adults treated with a first generation antipsychotic appears to be at least 3 times that observed with second generation antipsychotics like aripiprazole. The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotics increases. However, TD can develop, although much less commonly, after relatively brief periods at low doses or may arise after drug discontinuation. Antipsychotics may suppress the signs and symptoms of TD and thereby mask the underlying process; however, TD may also remit partially or completely if the antipsychotic is withdrawn. The effect that symptomatic suppression has upon the long-term course of TD is unknown. If signs and symptoms of TD appear, consider aripiprazole discontinuation. However, some patients may require treatment despite the presence of the syndrome.

    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. Complete a fall risk assessment when initiating an antipsychotic in those with diseases (e.g., neurological disease), conditions, or concurrent medication use that could exacerbate motor and sensory instability and reassess as needed with continued treatment. Pseudoparkinsonism was reported infrequently during trials of aripiprazole; use 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, 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).

    Poor metabolizers

    Aristada Initio (single dose extended-release intramuscular injection) should be avoided in known CYP2D6 poor metabolizers (CYP2D6 PMs). Dosage adjustments are recommended in known CYP2D6 PMs for all other formulations of aripiprazole (e.g., Abilify, Abilify Mycite, Abilify Maintena, Abilify Asimtufii, Aristada) due to the expected increases in aripiprazole exposure. Approximately 8% of Caucasians and 3% to 8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as CYP2D6 PMs.

    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 may be acceptable for some patients, a 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

    Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients; avoid use of aripiprazole if possible due to an increase in morbidity and mortality in elderly patients with dementia receiving antipsychotics. Deaths have typically resulted from heart failure, sudden death, or infections (primarily pneumonia). An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. A low starting dose is recommended for the older adult patient if aripiprazole is used. The Beers Criteria consider antipsychotics to be potentially inappropriate medications (PIMs) in elderly patients except for treating schizophrenia, bipolar disorder, and nausea/vomiting during chemotherapy. The Beers panel recommends avoiding antipsychotics in geriatric patients with delirium, dementia, or Parkinson's disease. Non-pharmacological strategies are first-line options for treating delirium- or dementia-related behavioral problems unless they have failed or are not possible and the patient is a substantial threat to self or others. If antipsychotic use is necessary in geriatrics with a history of falls or fractures, consider reducing the use of other CNS depressants and implement other fall risk strategies. Due to the potential for antipsychotic-induced hyponatremia and SIADH, sodium levels should be closely monitored when aripiprazole is initiated and after dose changes. According to the federal Omnibus Budget Reconciliation Act (OBRA) regulations in residents of long-term care facilities, antipsychotic therapy should only be initiated in a patient with behavioral or psychological symptoms of dementia (BPSD) when the patient is a danger to self or others or has symptoms due to mania or psychosis. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Antipsychotics are subject to periodic review for effectiveness, medical necessity, gradual dose reduction (GDR), or rationale for continued use. Refer to the OBRA guidelines for complete information.

    Neonates, pregnancy, pregnancy testing

    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 of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in exposed neonates. The complications have varied in severity and have ranged from self-limited to those requiring intensive care unit support and prolonged hospitalization. Carefully monitor neonates exhibiting signs or symptoms of extrapyramidal effects or withdrawal. The knowledge about long-term neurobehavioral effects in offspring is limited for all antipsychotic agents and requires further investigation. According to the American Psychiatric Association treatment guidelines for schizophrenia, consider pregnancy testing in women of childbearing potential prior to initiation of an antipsychotic. Data in human pregnancy with aripiprazole suggest that the risk of major malformations after first trimester exposure to aripiprazole is not significant compared to controls; the data are limited by relatively small numbers of exposed pregnancies studied. There is a pregnancy exposure registry that continues to monitor outcomes in pregnant patients exposed to aripiprazole and other atypical antipsychotics; information about the registry can be obtained at womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ or by calling 1-866-961-2388. It is not known if antipsychotics, through their effect on prolactin, would affect labor or obstetric delivery.

    Breast-feeding

    Aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, the effects on the breastfed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant exposure, and the risk of an untreated or inadequately treated condition. Milk to plasma ratios of approximately 0.18 to 0.2 have been estimated. However, there is a variation of about 11-fold in the relative infant dose (0.7% to 8.3%). Aripiprazole can accumulate in an infant due to the long elimination half-life of the drug (approximately 75 hours) and the immature hepatic and renal functions of the developing infant, particular if preterm or newborn. Data related to the safety of antipsychotics during breast-feeding are limited. It may be prudent to continue an existing antipsychotic regimen if ongoing treatment is deemed necessary during breast-feeding, since there is considerable individual variation in antipsychotic response. Alternate medications for consideration include olanzapine or quetiapine. Regardless of the antipsychotic used, closely monitor the breastfed infant for excessive drowsiness, lethargy, developmental delays, and other side effects. Combination treatment with antipsychotics may increase the risk of these adverse events. 

    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.

    Magnetic resonance imaging (MRI)

    Patients should be instructed to remove the Mycite topical patch, which is used with the aripiprazole tablet with sensor (Abilify Mycite tablet), before undergoing magnetic resonance imaging (MRI) and replace with a new patch as directed as soon as possible after the MRI. Metal components contained in the backing of some patch systems can overheat during an MRI scan and cause skin burns in the area where the patch is adhered. If there is skin irritation that occurs with the patch at anytime, instruct patients to remove the patch and notify their healthcare prescriber.

    Ensure correct formulation selection

    Medication errors, including substitution and dispensing errors, may occur when selecting between the distinct extended-release aripiprazole lauroxil intramuscular injections, Aristada and Aristada Initio. Dosing and medication errors may also possibly occur with Abilify Maintena injections (aripiprazole extended-release injections). Prescribers and health care professionals administering the drug should ensure correct formulation selection during prescribing and before administration. The various injections have distinct properties. For example, Aristada Initio is for single administration in contrast to Aristada which is a maintenance injection administered monthly, every 6 weeks, or every 8 weeks. Do not substitute Aristada Initio for Aristada since these products have different pharmacokinetic profiles.[60196]

    Laboratory test interference

    A laboratory test interference may occur with aripiprazole use. 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 consider confirmation by alternative tests such as gas chromatography/mass spectrometry.

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 0.1-0.9
    seizures / Delayed / 0-0.2
    rhabdomyolysis / Delayed / 0-0.1
    AV block / Early / 0-0.1
    myocardial infarction / Delayed / 0-0.1
    atrial fibrillation / Early / 0-0.1
    cardiac arrest / Early / 0-0.1
    atrial flutter / Early / 0-0.1
    suicidal ideation / Delayed / Incidence not known
    stroke / Early / Incidence not known
    diabetic ketoacidosis / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    laryngospasm / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    tardive dyskinesia / Delayed / Incidence not known
    neuroleptic malignant syndrome / Delayed / Incidence not known
    water intoxication / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known

    Moderate

    hyperglycemia / Delayed / 0-17.6
    constipation / Delayed / 2.0-11.0
    blurred vision / Early / 3.0-8.0
    urinary incontinence / Early / 1.0-5.0
    sinus tachycardia / Rapid / 2.0-2.0
    myoclonia / Delayed / 0.1-1.0
    peripheral edema / Delayed / 0-1.0
    orthostatic hypotension / Delayed / 0.2-1.0
    hyponatremia / Delayed / 0-1.0
    memory impairment / Delayed / 0.1-0.9
    delirium / Early / 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
    photophobia / Early / 0.1-0.9
    dyspnea / Early / 0.1-0.9
    elevated hepatic enzymes / Delayed / 0.1-0.9
    palpitations / Early / 0.1-0.9
    chest pain (unspecified) / Early / 0.1-0.9
    hypertension / Early / 0.1-0.9
    hypokalemia / Delayed / 0.1-0.9
    impotence (erectile dysfunction) / Delayed / 0.1-0.9
    complex sleep-related behaviors / Early / 0-0.1
    thrombocytopenia / Delayed / 0-0.1
    jaundice / Delayed / 0-0.1
    hyperbilirubinemia / Delayed / 0-0.1
    hepatitis / Delayed / 0-0.1
    QT prolongation / Rapid / 0-0.1
    angina / Early / 0-0.1
    hyperprolactinemia / Delayed / 0-0.1
    priapism / Early / 0-0.1
    confusion / Early / Incidence not known
    impaired cognition / Early / Incidence not known
    depression / Delayed / Incidence not known
    impulse control symptoms / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    fecal incontinence / Early / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    hypertriglyceridemia / Delayed / Incidence not known
    hyperlipidemia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    hyperthermia / Delayed / Incidence not known
    heat intolerance / Early / 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
    skin irritation / Early / 12.4-12.4
    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 / 4.0-5.0
    diarrhea / Early / 3.0-4.0
    weight loss / Delayed / 1.0-4.0
    dental pain / Delayed / 4.0-4.0
    musculoskeletal pain / Early / 1.0-4.0
    arthralgia / Delayed / 1.0-4.0
    myalgia / Early / 2.0-4.0
    abdominal pain / Early / 3.0-3.0
    cough / Delayed / 3.0-3.0
    irritability / Delayed / 2.0-2.0
    epistaxis / Delayed / 2.0-2.0
    rash / Early / 0.1-2.0
    pruritus / Rapid / 0.1-1.0
    libido decrease / Delayed / 0.1-0.9
    gastroesophageal reflux / Delayed / 0.1-0.9
    nocturia / Early / 0.1-0.9
    nasal congestion / Early / 0.1-0.9
    alopecia / Delayed / 0.1-0.9
    photosensitivity / Delayed / 0.1-0.9
    hirsutism / Delayed / 0.1-0.9
    hyperhidrosis / Delayed / 0.1-0.9
    syncope / Early / 0.2-0.5
    somnambulism / Early / 0-0.1
    libido increase / Delayed / 0-0.1
    diplopia / Early / 0-0.1
    urticaria / Rapid / 0-0.1
    amenorrhea / Delayed / 0-0.1
    orgasm dysfunction / Delayed / 0-0.1
    mastalgia / Delayed / 0-0.1
    gynecomastia / Delayed / 0-0.1
    menstrual irregularity / Delayed / 0-0.1
    asthenia / Delayed / 1.0
    anorexia / Delayed / 1.0
    injection site reaction / Rapid / 1.0
    psychomotor impairment / Early / Incidence not known
    hiccups / Early / Incidence not known
    polydipsia / Early / Incidence not known
    hypothermia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) Abarelix carries an established risk for QT prolongation. Prescribers need to weigh the potential benefits and risks of abarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Abiraterone: (Moderate) Because aripiprazole is partially metabolized by CYP2D6, patients should be carefully monitored for aripiprazole-related adverse reactions during concurrent use of a moderate CYP2D6 inhibitor such as abiraterone. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 inhibitor and abiraterone 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 inhibitor and abiraterone 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 or Aristada Initio during use of a moderate CYP2D6 inhibitor alone.
    Acarbose: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Acebutolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Caffeine; Pyrilamine: (Moderate) 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.
    Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and aripiprazole due to the risk for additive CNS depression.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Drugs that can cause CNS depression, including dichloralphenazone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness if used concomitantly with atypical antipsychotics.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Oxycodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) 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.
    Acetaminophen; Pentazocine: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
    Acrivastine; Pseudoephedrine: (Moderate) 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.
    Adagrasib: (Major) Avoid concomitant use of aripiprazole and adagrasib; concomitant use increases aripiprazole concentrations, which may increase the risk for aripiprazole-related adverse effects, and increases the risk for QT/QTc prolongation and torsade de pointes (TdP). If concomitant use is necessary, an aripiprazole dosage reduction may be required and recommendations for dosage adjustments vary by aripiprazole dosage form. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose. Avoid the use of Aristada Initio because the dose of Aristada Initio cannot be modified. Adults receiving Abilify Maintena should have their dosage reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Reduce the dose of Aristada to the next lower strength. Additional dosage modifications may be required for patients that are poor CYP2D6 metabolizers; see product labeling for details. Both medications increase the risk for QT/QTc prolongation. In addition to adjusting the aripiprazole dosage, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Aripiprazole is a substrate for CYP2D6 and CYP3A; adagrasib is a strong CYP3A inhibitor and a moderate CYP2D6 inhibitor. Based on simulation studies, a 3-fold increase in aripiprazole exposure is expected when CYP2D6 poor metabolizers are administered a strong CYP3A inhibitor. A 4.5-fold increase in aripiprazole exposure is expected when CYP2D6 extensive metabolizers receive both a strong CYP3A and CYP2D6 inhibitor.
    Albiglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Aldesleukin, IL-2: (Moderate) 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 (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 or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor.
    Alfentanil: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Alfuzosin: (Moderate) Concomitant use of aripiprazole and alfuzosin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Alogliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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; Pioglitazone: (Moderate) Monitor blood glucose during concomitant aripiprazole and pioglitazone use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Alpha-glucosidase Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alprazolam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
    Amifampridine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
    Amiloride: (Moderate) Monitor blood pressure and adjust amiloride dose accordingly as aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust amiloride dose accordingly as aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amiodarone: (Major) Concomitant use of amiodarone and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase aripiprazole exposure and the risk for other aripiprazole-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concomitant use is necessary, reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Adults receiving a combination amiodarone 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 or Aristada Initio during use of a dual moderate CYP2D6/CYP3A4 inhibitor. Aripiprazole is a substrate for CYP2D6 and CYP3A4; amiodarone is a moderate CYP2D6 and CYP3A4 inhibitor.
    Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with aripiprazole. Amisulpride causes dose- and concentration- dependent QT prolongation. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Amitriptyline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
    Amlodipine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Atorvastatin: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Benazepril: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Celecoxib: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of celecoxib. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A inhibitor. Adults receiving a combination of a CYP3A inhibitor and celecoxib 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; celecoxib is a weak CYP2D6 inhibitor. (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Olmesartan: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Valsartan: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Amobarbital: (Major) 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 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 Abilify Maintena 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, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
    Amoxapine: (Moderate) 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; Omeprazole: (Major) 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 partially 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving Abilify Maintena 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 Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Anagrelide: (Moderate) Concomitant use of aripiprazole and anagrelide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Angiotensin II receptor antagonists: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Angiotensin-converting enzyme inhibitors: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Apalutamide: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when a potent CYP3A4 inducer, such as apalutamide, 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 apalutamide is discontinued, the aripiprazole dose in adults should be reduced to the original dose over 1 to 2 weeks. Avoid concurrent use of Abilify Maintena with apalutamide when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving Aristada with apalutamide, no dosage adjustment is necessary for the 662 mg, 882 mg, or 1,064 mg dose; increase the 441 mg dose to 662 mg if apalutamide is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers.
    Apomorphine: (Moderate) Use apomorphine and aripiprazole with caution due to a risk for QT prolongation and sedation. Apomorphine and aripiprazole may decrease the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent during coadministration.
    Aprepitant, Fosaprepitant: (Moderate) Caution is recommended during coadministration of aripiprazole, a partial CYP3A4 substrate, and aprepitant. A 3-day course of oral aprepitant with another CYP3A4 substrate resulted in an increased AUC of the substrate during the initial days following treatment (e.g., 4 days), then the substrate AUC declined between Days 8 and 15. Single doses of oral aprepitant or IV fosaprepitant have demonstrated weak CYP3A4 inhibition that is not considered clinically relevant. If these agents are coadministered, the patient should be carefully monitored for aripiprazole-related adverse reactions such as QT prolongation or torsade de pointes (TdP). 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 (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 or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor.
    Armodafinil: (Moderate) 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. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Arsenic Trioxide: (Major) 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: (Major) 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 one-half of the usual dose in patients receiving potent inhibitors of CYP2D6 such as lumefantrine. Adults receiving 300 mg or 400 mg of Abilify Maintena should have a dose reduction to 200 mg or 300 mg, respectively, during coadministration of a potent CYP2D6 inhibitor if used for more than 14 days. 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. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. 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. 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. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP2D6 inhibitors because the dose of Aristada Initio cannot be modified.
    Asciminib: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of asciminib. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and asciminib 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 or Aristada Initio during use of a weak or moderate CYP3A inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; asciminib is a weak CYP3A inhibitor.
    Asenapine: (Major) 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: (Major) 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 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 Abilify Maintena 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, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) 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 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 Abilify Maintena 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, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination. (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Atazanavir: (Major) Because aripiprazole is partially 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Atazanavir; Cobicistat: (Major) Because aripiprazole is partially 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified. (Major) The plasma concentrations of aripiprazole, a CYP3A4 and CYP2D6 substrate, may be elevated when administered concurrently with cobicistat, a CYP2D6 inhibitor and strong CYP3A4 inhibitor. The manufacturer of aripiprazole recommends that 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. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor, such as cobicistat, for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Atenolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Atenolol; Chlorthalidone: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Atomoxetine: (Moderate) Concomitant use of aripiprazole and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with aripiprazole can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Avacopan: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of avacopan. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and avacopan 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 or Aristada Initio during use of a weak or moderate CYP3A inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; avacopan is a weak CYP3A inhibitor.
    Azithromycin: (Major) Concomitant use of azithromycin and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Barbiturates: (Major) 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 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 Abilify Maintena 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, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
    Bedaquiline: (Major) 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; Opium: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Belumosudil: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of belumosudil. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and belumosudil 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 or Aristada Initio during use of a mild to moderate CYP3A inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; belumosudil is a weak CYP3A inhibitor.
    Bendroflumethiazide; Nadolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Benzodiazepines: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
    Berotralstat: (Major) Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients receiving berotralstat. Monitor for aripiprazole-related adverse reactions during concurrent use of berotralstat. Adults receiving berotralstat 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 or Aristada Initio during use of moderate CYP2D6/CYP3A4 inhibitors. Aripiprazole is a substrate for CYP2D6 and CYP3A4; berotralstat is a moderate CYP2D6 and moderate CYP3A4 inhibitor.
    Beta-adrenergic blockers: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Betaxolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Bexarotene: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as bexarotene 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 Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Bicalutamide: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of bicalutamide. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and bicalutamide 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 or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A4; bicalutamide is a weak CYP3A4 inhibitor.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Bisoprolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Brexpiprazole: (Contraindicated) 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: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Bromocriptine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
    Brompheniramine: (Moderate) 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: (Moderate) 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; Phenylephrine: (Moderate) 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; Phenylephrine: (Moderate) 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: (Moderate) 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; Dextromethorphan: (Moderate) 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.
    Buprenorphine: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of 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: (Major) 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: (Major) Reduce the oral aripiprazole dosage by one-half of the usual dose during coadministration of bupropion. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A4 inhibitor. Avoid concurrent use of Aristada Initio and bupropion because the dose of Aristada Initio cannot be modified. For other long-acting aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with strong CYP2D6 inhibitors and combined strong CYP2D6/CYP3A4 inhibitors; the recommendations are dependent on the aripiprazole IM depot dosage, the product given, and the duration of the concomitant inhibitors as specified in the product labels. Aripiprazole is a substrate for CYP2D6 and CYP3A4; bupropion is a strong CYP2D6 inhibitor. Based on simulation studies, a 4.5-fold increase in aripiprazole exposure is expected when CYP2D6 extensive metabolizers are administered both a strong CYP2D6 and CYP3A4 inhibitor.
    Bupropion; Naltrexone: (Major) Reduce the oral aripiprazole dosage by one-half of the usual dose during coadministration of bupropion. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A4 inhibitor. Avoid concurrent use of Aristada Initio and bupropion because the dose of Aristada Initio cannot be modified. For other long-acting aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with strong CYP2D6 inhibitors and combined strong CYP2D6/CYP3A4 inhibitors; the recommendations are dependent on the aripiprazole IM depot dosage, the product given, and the duration of the concomitant inhibitors as specified in the product labels. Aripiprazole is a substrate for CYP2D6 and CYP3A4; bupropion is a strong CYP2D6 inhibitor. Based on simulation studies, a 4.5-fold increase in aripiprazole exposure is expected when CYP2D6 extensive metabolizers are administered both a strong CYP2D6 and CYP3A4 inhibitor.
    Buspirone: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant atypical antipsychotic and buspirone use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
    Butabarbital: (Major) 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 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 Abilify Maintena 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, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
    Butalbital; Acetaminophen: (Major) 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 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 Abilify Maintena 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, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
    Butalbital; Acetaminophen; Caffeine: (Major) 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 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 Abilify Maintena 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, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) 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 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 Abilify Maintena 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, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination. (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as aripiprazole, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
    Cabergoline: (Moderate) Cabergoline should not be coadministered with aripiprazole due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of aripiprazole may diminish the prolactin-lowering ability of cabergoline while the dopamine agonist effects of cabergoline may exacerbate a psychotic disorder, reducing the effectiveness of antipsychotics such as aripiprazole.
    Cabotegravir; Rilpivirine: (Moderate) Concomitant use of aripiprazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Minor) 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.
    Canagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and aripiprazole. Concurrent use may result in additive CNS depression.
    Carbamazepine: (Major) Because aripiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when a potent 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 discontinued, the oral aripiprazole dose should be reduced to the original level over 1 to 2 weeks. Avoid concurrent use of Abilify Maintena with a strong CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving Aristada with a strong CYP3A4 inducer, no dose adjustment is necessary for the 662 mg, 882 mg, or 1,064 mg dose; increase the 441 mg dose to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers.
    Carbidopa; Levodopa: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
    Carbidopa; Levodopa; Entacapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease. (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
    Carbinoxamine: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) The risk of adverse effects may be increased during concurrent use of cariprazine with other antipsychotics, such as aripiprazole. Similar to other antipsychotics, cariprazine administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. The incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, but the risk appears to be increased.
    Carteolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Carvedilol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Celecoxib: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of celecoxib. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A inhibitor. Adults receiving a combination of a CYP3A inhibitor and celecoxib 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; celecoxib is a weak CYP2D6 inhibitor.
    Celecoxib; Tramadol: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of celecoxib. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A inhibitor. Adults receiving a combination of a CYP3A inhibitor and celecoxib 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; celecoxib is a weak CYP2D6 inhibitor. (Major) Reserve concomitant use of tramadol and aripiprazole for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation as well as seizures. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, seizures, and death.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and aripiprazole. Concurrent use may result in additive CNS depression.
    Central-acting adrenergic agents: (Minor) 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: (Major) Avoid use of aripiprazole with ceritinib if possible due to the risk of QT prolongation. Ceritinib causes concentration-dependent QT prolongation. Prolongation of the QT interval has also occurred during therapeutic use of aripiprazole and following overdose. If concurrent use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. In addition, because aripiprazole is partially 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 ceritinib. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if ceritinib is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of ceritinib for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Because aripiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving ceritinib or patients receiving a combination of ceritinib 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 Abilify Maintena who are PMs and receiving ceritinib should have a dose reduction to 200 mg/month IM. Patients receiving a combination of ceritinib and a 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. Adults receiving Aristada who are PMs of CYP2D6 and receiving ceritinib for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 mg, combined use of a strong CYP2D6 inhibitor and ceritinib for more than 14 days should be avoided; no dose adjustment is needed in patients taking 441 mg, if tolerated. Avoid concurrent use of Aristada Initio and ceritinib because the dose of Aristada Initio cannot be modified.
    Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
    Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
    Cetrorelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs including cetrorelix.
    Charcoal: (Major) 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: (Moderate) 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: (Major) 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) 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. 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. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Chlorcyclizine: (Moderate) Additive CNS effects like drowsiness may be seen when combining sedating H1-blockers with atypical antipsychotics.
    Chlordiazepoxide: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
    Chlordiazepoxide; Amitriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
    Chlordiazepoxide; Clidinium: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
    Chloroquine: (Major) Avoid coadministration of chloroquine with aripiprazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorpromazine: (Major) 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: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of cimetidine. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving cimetidine 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. Aripiprazole is a substrate for CYP2D6 and CYP3A; cimetidine is a weak CYP2D6 inhibitor and weak CYP3A inhibitor.
    Cinacalcet: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of cinacalcet. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A inhibitor. Adults receiving a combination of a CYP3A inhibitor and cinacalcet 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; cinacalcet is a moderate CYP2D6 inhibitor.
    Ciprofloxacin: (Major) Concomitant use of aripiprazole and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use also increases aripiprazole exposure. Aripiprazole is a substrate for CYP2D6 and CYP3A; ciprofloxacin is a moderate CYP3A inhibitor.
    Cisapride: (Contraindicated) Avoid concomitant use of cisapride and aripiprazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Citalopram: (Major) Concomitant use of aripiprazole and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase aripiprazole exposure and other aripiprazole-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Also monitor for aripiprazole-related adverse reactions during concurrent use. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A4 inhibitor. Adults receiving a combination of a CYP3A4 inhibitor and citalopram 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A4; citalopram is a weak CYP2D6 inhibitor.
    Clarithromycin: (Major) 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 partially 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving Abilify Maintena 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 Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Clemastine: (Moderate) 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: (Moderate) Clobazam, a benzodiazepine, should be combined cautiously with atypical antipsychotics because of the potential for additive CNS depressant effects. Antipsychotics may also lower the seizure threshold, which might effect the efficacy of clobazam to treat seizures. Clobazam is a weak inducer of CYP3A4 and may reduce the efficacy of atypical antipsychotics that are significantly metabolized by CYP3A4; consult the atypical antipsychotic product labeling for clinical relevance.
    Clofazimine: (Moderate) Concomitant use of clofazimine and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Clomipramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
    Clonazepam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
    Clorazepate: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
    Clozapine: (Major) 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: (Major) The plasma concentrations of aripiprazole, a CYP3A4 and CYP2D6 substrate, may be elevated when administered concurrently with cobicistat, a CYP2D6 inhibitor and strong CYP3A4 inhibitor. The manufacturer of aripiprazole recommends that 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. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor, such as cobicistat, for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Codeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of aripiprazole and promethazine may increase the risk of CNS depression and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for unusual drowsiness and excess sedation and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Promethazine: (Moderate) Concomitant use of aripiprazole and promethazine may increase the risk of CNS depression and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for unusual drowsiness and excess sedation and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    COMT inhibitors: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Conivaptan: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of conivaptan. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and conivaptan 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 or Aristada Initio during use of a weak or moderate CYP3A inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; conivaptan is a moderate CYP3A inhibitor.
    Crizotinib: (Major) Avoid coadministration of crizotinib with aripiprazole due to the risk of QT prolongation. Because aripiprazole is partially metabolized by CYP3A4, increased aripiprazole blood levels may also occur if the drug is coadministered with moderate inhibitors of CYP3A such as crizotinib. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. The patient should also 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 or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor. Crizotinib has been associated with concentration-dependent QT prolongation. Prolongation of the QT interval has occurred during therapeutic use of aripiprazole as well as following overdose.
    Cyclizine: (Moderate) 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.
    Cyproheptadine: (Moderate) 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.
    Dacomitinib: (Major) Dacomitinib, a strong 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, QT prolongation, and torsade de pointes (TdP). The manufacturer of aripiprazole recommends that the oral aripiprazole dose be reduced to one-half of the usual dose when coadministered with strong CYP2D6 inhibitors. Adults receiving 300 mg or 400 mg of Abilify Maintena should have a dose reduction to 200 mg or 300 mg, respectively, during coadministration of a strong CYP2D6 inhibitor if used for more than 14 days. 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. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. 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. 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. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP2D6 inhibitors because the dose of Aristada Initio cannot be modified. Aripiprazole dosage adjustments are not required when aripiprazole is added as adjunctive treatment to antidepressants for major depressive disorder provided that the manufacturer's dosing guidelines for this indication are followed.
    Danazol: (Moderate) Because aripiprazole is partially 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. 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. 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 or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor.
    Dapagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Darifenacin: (Moderate) Carefully monitor for aripiprazole-related adverse reactions if coadministered with darifenacin. Darifenacin is a moderate CYP2D6 inhibitor and may increase exposure to aripiprazole, a CYP2D6 substrate. 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 (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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor.
    Darunavir: (Major) Because aripiprazole is partially 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) 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. 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. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Darunavir; Cobicistat: (Major) Because aripiprazole is partially 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) 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. 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. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified. (Major) The plasma concentrations of aripiprazole, a CYP3A4 and CYP2D6 substrate, may be elevated when administered concurrently with cobicistat, a CYP2D6 inhibitor and strong CYP3A4 inhibitor. The manufacturer of aripiprazole recommends that 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. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor, such as cobicistat, for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Because aripiprazole is partially 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) 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. 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. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified. (Major) The plasma concentrations of aripiprazole, a CYP3A4 and CYP2D6 substrate, may be elevated when administered concurrently with cobicistat, a CYP2D6 inhibitor and strong CYP3A4 inhibitor. The manufacturer of aripiprazole recommends that 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. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor, such as cobicistat, for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) 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. Patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 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. Adults receiving Abilify Maintena who are PMs and receiving a strong CYP3A4 inhibitor, such as ritonavir, should have a dose reduction to 200 mg/month IM. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Dasatinib: (Moderate) Concomitant use of aripiprazole and dasatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Degarelix: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., degarelix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Delavirdine: (Major) 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. 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 CYP3A4 inhibitor, such as delavirdine, for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 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 Abilify Maintena 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 Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Desipramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
    Deutetrabenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and aripiprazole. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and aripiprazole is a partial dopamine agonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of aripiprazole and deutetrabenazine. Concurrent use may result in additive CNS depression.
    Dexamethasone: (Moderate) 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 Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during concurrent use of a mild or moderate CYP3A4 inducer.
    Dexchlorpheniramine: (Moderate) 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: (Moderate) 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.
    Dextromethorphan; Bupropion: (Major) Reduce the oral aripiprazole dosage by one-half of the usual dose during coadministration of bupropion. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A4 inhibitor. Avoid concurrent use of Aristada Initio and bupropion because the dose of Aristada Initio cannot be modified. For other long-acting aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with strong CYP2D6 inhibitors and combined strong CYP2D6/CYP3A4 inhibitors; the recommendations are dependent on the aripiprazole IM depot dosage, the product given, and the duration of the concomitant inhibitors as specified in the product labels. Aripiprazole is a substrate for CYP2D6 and CYP3A4; bupropion is a strong CYP2D6 inhibitor. Based on simulation studies, a 4.5-fold increase in aripiprazole exposure is expected when CYP2D6 extensive metabolizers are administered both a strong CYP2D6 and CYP3A4 inhibitor.
    Dextromethorphan; Quinidine: (Contraindicated) Avoid use of aripiprazole with quinidine unless the benefit outweighs the risk. Quinidine is generally contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as aripiprazole, as the effects on the QT interval may be increased. Manufacturer recommendations for this combination have varied. Do not use the combination product of dextromethorphan; quinidine with aripiprazole. The manufacturers of aripiprazole products do not contraindicate use of quinidine, but recommend dosage adjustments of aripiprazole when used with potent CYP2D6 inhibitors, such as quinidine. For example, the oral aripiprazole dose should be reduced by 50%. Injectable forms of aripiprazole require dose adjustment when the potent CYP2D6 inhibitor will be used for more than 14 days. See the manufacturer prescribing information for detailed recommendations. Both aripiprazole and quinidine are associated with QT prolongation. Increased aripiprazole exposure is likely when a potent CYP2D6 inhibitor like quinidine is used concurrently. 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%.
    Diazepam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
    Diazoxide: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
    Diltiazem: (Major) Monitor blood pressure and for aripiprazole-related adverse reactions during concurrent use of diltiazem. Due to its alpha-adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents; a diltiazem dose adjustment may be needed. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and diltiazem 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 or Aristada Initio during use of a weak or moderate CYP3A inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; diltiazem is a moderate CYP3A inhibitor.
    Dimenhydrinate: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of dimenhydrinate and aripiprazole due to the risk for additive CNS depression.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with aripiprazole can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Disopyramide: (Major) Concomitant use of disopyramide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Dofetilide: (Major) Concomitant use of dofetilide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Dolasetron: (Moderate) Concomitant use of aripiprazole and dolasetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Dolutegravir; Rilpivirine: (Moderate) Concomitant use of aripiprazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Donepezil: (Moderate) Concomitant use of aripiprazole and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Donepezil; Memantine: (Moderate) Concomitant use of aripiprazole and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Dorzolamide; Timolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Doxazosin: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Doxepin: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
    Doxylamine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and aripiprazole due to the risk for additive CNS depression.
    Doxylamine; Pyridoxine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and aripiprazole due to the risk for additive CNS depression.
    Dronabinol: (Moderate) Drugs that can cause CNS depression such as dronabinol, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Dronedarone: (Contraindicated) Avoid concomitant use of dronedarone and aripiprazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Droperidol: (Major) According to the manufacturer of droperidol, any drug known to have the potential to prolong the QT interval should not be used together with droperidol. The product labeling contains a boxed warning regarding the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. If concurrent use is unavoidable, extreme caution is recommended.
    Dulaglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Duloxetine: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of duloxetine. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A inhibitor. Adults receiving a combination of a CYP3A inhibitor and duloxetine 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; duloxetine is a moderate CYP2D6 inhibitor.
    Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with aripiprazole as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. QT prolongation has 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. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with aripiprazole as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. QT prolongation has 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. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with aripiprazole as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. QT prolongation has 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. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Elagolix: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during coadministration of a CYP3A4 inducer, such as elagolix. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. A dose adjustment of aripiprazole may be needed. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during coadministration of a CYP3A4 inducer, such as elagolix. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. A dose adjustment of aripiprazole may be needed. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Elbasvir; Grazoprevir: (Moderate) Administering aripiprazole with grazoprevir may result in elevated aripiprazole plasma concentrations. Aripiprazole is a substrate of CYP3A4 and grazoprevir is a weak CYP3A inhibitor. 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 (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.
    Eliglustat: (Major) Coadminister aripiprazole and eliglustat cautiously and with close monitoring. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations and aripiprazole has the potential for QT prolongation with both therapeutic use and overdose. In addition, because aripiprazole is partially metabolized by CYP2D6, increased aripiprazole plasma concentrations may occur during concurrent use of CYP2D6 inhibitors such as eliglustat. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) The plasma concentrations of aripiprazole, a CYP3A4 and CYP2D6 substrate, may be elevated when administered concurrently with cobicistat, a CYP2D6 inhibitor and strong CYP3A4 inhibitor. The manufacturer of aripiprazole recommends that 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. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor, such as cobicistat, for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The plasma concentrations of aripiprazole, a CYP3A4 and CYP2D6 substrate, may be elevated when administered concurrently with cobicistat, a CYP2D6 inhibitor and strong CYP3A4 inhibitor. The manufacturer of aripiprazole recommends that 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. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor, such as cobicistat, for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Empagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concomitant use of aripiprazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of aripiprazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
    Encorafenib: (Major) Concomitant use of encorafenib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Entacapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Entrectinib: (Major) Concomitant use of entrectinib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Enzalutamide: (Major) Because aripiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when a potent CYP3A4 inducer, such as enzalutamide, 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 discontinued, the aripiprazole dose should be reduced to the original level over 1 to 2 weeks. Avoid concurrent use of Abilify Maintena with a strong CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving Aristada with a strong CYP3A4 inducer for more than 14 days, no dose adjustment is necessary for the 662 mg or the 882 mg dose; increase the 441 mg dose to 662 mg. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers.
    Eplerenone: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Epoprostenol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Eribulin: (Major) Concomitant use of aripiprazole and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ertugliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Erythromycin: (Major) 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 or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor.
    Escitalopram: (Major) Concomitant use of aripiprazole and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Monitor for aripiprazole-related adverse reactions during concurrent use. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A inhibitor. Adults receiving a combination of a CYP3A inhibitor and escitalopram 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; escitalopram is a moderate CYP2D6 inhibitor.
    Esketamine: (Moderate) Closely monitor patients receiving esketamine and aripiprazole for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Eslicarbazepine: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. 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. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Esmolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Estazolam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
    Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as antipsychotics, to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Antipsychotics with a higher incidence of sedation, such as olanzapine, clozapine, quetiapine, lurasidone, chlorpromazine, and thioridazine, are more likely to interact with eszopiclone. In one evaluation, concurrent use of eszopiclone and olanzapine reduced psychomotor function as measured by the Digit Symbol Substitution Test (DSST).
    Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
    Etravirine: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during use of a CYP3A4 inducer, such as etravirine. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
    Everolimus: (Major) Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response if coadministration with everolimus is necessary; monitor for aripiprazole-related adverse reactions. Adults receiving everolimus 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. Aripiprazole is a substrate for CYP2D6 and CYP3A4; everolimus is a weak CYP3A4 inhibitor as well as a competitive inhibitor of CYP2D6.
    Exenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Famotidine: (Minor) 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.
    Fedratinib: (Major) Reduce the oral aripiprazole dose to one-quarter (25%) of the usual dose in patients receiving fedratinib as aripiprazole exposure and adverse effects may be increased. Adults receiving this combination 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 or Aristada Initio during concurrent use. Aripiprazole is a CYP3A4 and CYP2D6 substrate; fedratinib is a moderate inhibitor of both CYP3A4 and CYP2D6.
    Felodipine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and aripiprazole. Concurrent use may result in additive CNS depression.
    Fenoldopam: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Fentanyl: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Fingolimod: (Moderate) Concomitant use of aripiprazole and fingolimod may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Flecainide: (Major) Concomitant use of aripiprazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Fluconazole: (Contraindicated) Avoid use of aripiprazole with fluconazole unless the benefit outweighs the risk of QT prolongation or other side effects. Conflicting recommendations are available from the manufacturers of the drugs. According to the manufacturer of fluconazole, coadministration of drugs known to prolong the QT interval and which are CYP3A4 substrates, such as aripiprazole, is contraindicated in patients receiving fluconazole. Metabolism of aripiprazole occurs mainly through CYP3A4 and CYP2D6. Both fluconazole and aripiprazole have been associated with QT prolongation. The manufacturers of aripiprazole products do not contraindicate use of fluconazole, but do recommend dosage adjustments of oral aripiprazole when used with CYP3A4 inhibitors such as fluconazole. Manufacturers of aripiprazole injections recommend adjustments when a potent CYP3A4 inhibitor will be used for more than 14 days. See the manufacturer prescribing information for detailed recommendations.
    Fluoxetine: (Major) Reduce the oral aripiprazole dosage by one-half of the usual dose in patients receiving strong CYP2D6 inhibitors such as fluoxetine. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A4 inhibitor, as aripiprazole is also metabolized by CYP3A4. Addtionally, aripiprazole and fluoxetine are both associated with prolongation of the QT interval; caution and close monitoring are recommended. Avoid concurrent use of Aristada Initio and fluoxetine because the dose of Aristada Initio cannot be modified. For other long-active aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with strong CYP2D6 inhibitors and combined strong CYP2D6/CYP3A4 inhibitors; the recommendations are dependent on the aripiprazole IM depot dosage, the product given, and the duration of the concomitant inhibitors as specified in the product labels.
    Fluphenazine: (Major) 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: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
    Fluvoxamine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and aripiprazole. Coadminister with caution. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Fluvoxamine is an inhibitor of CYP3A4 and CYP2D6, which may result in decreased clearance of substrates of these isoenzymes including aripiprazole. Decreased metabolism of aripiprazole may lead to clinically important adverse reactions that are associated with antipsychotic use, such as extrapyramidal symptoms. 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 or Aristada Initio during use of a mild to moderate CYP2D6 or CYP3A4 inhibitor. Aripiprazole dosage adjustments are not required when aripiprazole is added as adjunctive treatment to antidepressants for major depressive disorder provided that the manufacturer's dosing guidelines for this indication are followed.
    Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
    Fosamprenavir: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of fosamprenavir. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and fosamprenavir 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 or Aristada Initio during use of a weak or moderate CYP3A inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; fosamprenavir is a moderate CYP3A inhibitor.
    Foscarnet: (Major) Concomitant use of aripiprazole and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Fosphenytoin: (Major) Double the usual oral aripiprazole dosage over 1 to 2 weeks during coadministration of fosphenytoin. Carefully monitor the patient for evidence of a decrease in aripiprazole efficacy and make subsequent dose adjustments based upon clinical response. When fosphenytoin is discontinued, the oral aripiprazole dose in adults should be reduced to the previous dose over 1 to 2 weeks. Avoid concurrent use of Aristada Initio and fosphenytoin because the dose of Aristada Initio cannot be modified. Avoid concurrent use of Abilify Maintena with fosphenytoin when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving Aristada with a strong CYP3A4 inducer, no dosage adjustment is necessary for the 662 mg, 882 mg, or 1,064 mg dose; increase the 441 mg dose to 662 mg if the CYP3A4 inducer is added for more than 2 weeks. Aripiprazole is metabolized by CYP3A4; fosphenytoin is a strong CYP3A4 inducer.
    Fostemsavir: (Moderate) Concomitant use of aripiprazole and fostemsavir may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
    Gabapentin: (Moderate) Monitor for respiratory depression and sedation during concomitant aripiprazole and gabapentin use; consider starting gabapentin at a low dose. Concomitant use increases the risk for additive CNS depression.
    Ganirelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to ganirelix, a gonadotropin-releasing hormone (GnRH) analog.
    Gefitinib: (Moderate) Because aripiprazole is partially metabolized by CYP2D6, patients should be carefully monitored for aripiprazole-related adverse reactions during concurrent use of a CYP2D6 inhibitor such as gefitinib. 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. 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor.
    Gemifloxacin: (Moderate) Concomitant use of aripiprazole and gemifloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Gemtuzumab Ozogamicin: (Moderate) Concomitant use of aripiprazole and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Gilteritinib: (Moderate) Concomitant use of aripiprazole and gilteritinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Glasdegib: (Major) Avoid coadministration of glasdegib with aripiprazole due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Glimepiride; Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Goserelin: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., goserelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Granisetron: (Moderate) Concomitant use of aripiprazole and granisetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Grapefruit juice: (Moderate) 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.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Halogenated Anesthetics: (Major) Concomitant use of aripiprazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Haloperidol: (Moderate) Caution is advisable when combining haloperidol concurrently with aripiprazole as concurrent use may increase the risk of QT prolongation and antipsychotic-related adverse effects. It may be advisable to initiate treatment with lower dosages if combination therapy is necessary as the risk of adverse effects(e.g., drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, cardiac conduction abnormalities, seizures) may be increased. A dosage reduction of aripiprazole may be necessary in patients receiving concomitant haloperidol and a CYP3A4 inhibitor. Haloperidol is a CYP2D6 inhibitor that has been associated with QT prolongation and torsade de pointes (TdP). Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Aripiprazole is partially metabolized through CYP2D6; QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In patients receiving aripiprazole with haloperidol and a CYP3A4 inhibitor, the oral aripiprazole dose should be reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 haloperidol 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 or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor.
    Histrelin: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydralazine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydromorphone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Hydroxyzine: (Moderate) Concomitant use of aripiprazole and hydroxyzine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Also, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression.
    Ibuprofen; Famotidine: (Minor) 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.
    Ibuprofen; Oxycodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Ibutilide: (Major) Concomitant use of ibutilide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Idelalisib: (Major) If possible, avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with aripiprazole, a CYP3A substrate, as aripiprazole toxicities may be significantly increased. If these drugs must be used together, 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 CYP3A4. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) 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. 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. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Iloperidone: (Major) 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: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Imatinib: (Major) 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 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 or Aristada Initio during use of a mild to moderate CYP3A4 and CYP2D6 inhibitor.
    Imipramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
    Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Indinavir: (Major) Because aripiprazole is partially 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) 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. 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. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with aripiprazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Insulins: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with aripiprazole may result in increased serum concentrations of aripiprazole. Aripiprazole is a substrate of CYP3A4 and isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. 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 (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 or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor.
    Isoniazid, INH: (Moderate) Administering aripiprazole with isoniazid may result in elevated aripiprazole plasma concentrations. Aripiprazole is a substrate of CYP3A4 and isoniazid is a weak CYP3A inhibitor. 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 (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.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when a potent 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 discontinued, the aripiprazole dose in adults should be reduced to the original dose over 1 to 2 weeks. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving Aristada with a strong CYP3A4 inducer, no dosage adjustment is necessary for the 662 mg, 882 mg, or 1,064 mg dose; increase the 441 mg dose to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. (Moderate) Administering aripiprazole with isoniazid may result in elevated aripiprazole plasma concentrations. Aripiprazole is a substrate of CYP3A4 and isoniazid is a weak CYP3A inhibitor. 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 (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.
    Isoniazid, INH; Rifampin: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when a potent 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 discontinued, the aripiprazole dose in adults should be reduced to the original dose over 1 to 2 weeks. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving Aristada with a strong CYP3A4 inducer, no dosage adjustment is necessary for the 662 mg, 882 mg, or 1,064 mg dose; increase the 441 mg dose to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. (Moderate) Administering aripiprazole with isoniazid may result in elevated aripiprazole plasma concentrations. Aripiprazole is a substrate of CYP3A4 and isoniazid is a weak CYP3A inhibitor. 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 (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.
    Isradipine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Istradefylline: (Moderate) Administering aripiprazole with istradefylline 40 mg daily may result in elevated aripiprazole plasma concentrations. Aripiprazole is a substrate of CYP3A4 and istradefylline administered as 40 mg daily is a weak CYP3A inhibitor. 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 (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. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
    Itraconazole: (Major) 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 dose. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) 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. 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. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with aripiprazole due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Ketoconazole: (Contraindicated) Avoid concomitant use of aripiprazole and ketoconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase aripiprazole exposure and other aripiprazole-related adverse effects. Ketoconazole is a strong CYP3A4 inhibitor. If concomitant use is medically necessary, reduce the oral aripiprazole dosage by one-half (50%) of the usual dose and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose in patients also receiving a CYP2D6 inhibitor or who are CYP2D6 poor metabolizers. Avoid concurrent use of Aristada Initio and ketoconazole because the dose of Aristada Initio cannot be modified. For other long-active aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with combined strong CYP2D6/CYP3A inhibitors; consult the product label as the recommendations are dependent on the IM dosage, the product given, and the duration of treatment with the concomitant inhibitors.
    Labetalol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Lamotrigine: (Minor) 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 100 mg/day to 400 mg/day who received ariprazole 10 mg/day to 30 mg/day for 7 days, followed by 30 mg/day for an additional 7 days.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) 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 partially 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 Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. 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 (25%) of the usual dose with subsequent adjustments based upon clinical response. Adult patients receiving Abilify Maintena 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 Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 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. Avoid concurrent use of Aristada Initio and strong CYP3A4 inhibitors because the dose of Aristada Initio cannot be modified.
    Lapatinib: (Moderate) Concomitant use of aripiprazole and lapatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Larotrectinib: (Moderate) Administering aripiprazole with larotrectinib may result in elevated aripiprazole plasma concentrations. Aripiprazole is a substrate of CYP3A4 and larotrectinib is a weak CYP3A inhibitor. 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 (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.
    Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and aripiprazole. Concurrent use may result in additive CNS depression.
    Lefamulin: (Major) Avoid coadministration of lefamulin with aripiprazole as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Lenacapavir: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of lenacapavir. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and lenacapavir 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 or Aristada Initio during use of a weak or moderate CYP3A inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A; lenacapavir is a moderate CYP3A inhibitor.
    Lenvatinib: (Major) Concomitant use of lenvatinib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Letermovir: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, patients should be carefully monitored for aripiprazole-related adverse reactions during concurrent use of a moderate CYP3A4 inhibitor such as letermovir. 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 (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 or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor. During coadministration of letermovir and cyclosporine, letermovir may exhibit more potent CYP3A4 inhibitory properties. When letermovir and cyclosporine are used concurrently with aripiprazole, consult the aripiprazole product information for dosage adjustments of aripiprazole necessary during use of a potent CYP3A4 inhibitor.
    Leuprolide: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Leuprolide; Norethindrone: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Levamlodipine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Levobetaxolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Levobunolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
    Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
    Levodopa: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
    Levofloxacin: (Moderate) Levofloxacin should be used cautiously with other agents that may prolong the QT interval or increase the risk of torsade de pointes (TdP). Levofloxacin has been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Levoketoconazole: (Contraindicated) Avoid concomitant use of aripiprazole and ketoconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase aripiprazole exposure and other aripiprazole-related adverse effects. Ketoconazole is a strong CYP3A4 inhibitor. If concomitant use is medically necessary, reduce the oral aripiprazole dosage by one-half (50%) of the usual dose and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose in patients also receiving a CYP2D6 inhibitor or who are CYP2D6 poor metabolizers. Avoid concurrent use of Aristada Initio and ketoconazole because the dose of Aristada Initio cannot be modified. For other long-active aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with combined strong CYP2D6/CYP3A inhibitors; consult the product label as the recommendations are dependent on the IM dosage, the product given, and the duration of treatment with the concomitant inhibitors.
    Levorphanol: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Linagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Liraglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Lithium: (Moderate) Concomitant use of aripiprazole and lithium may increase the risk of neuroleptic malignant syndrome (NMS) and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for neurotoxicity during concomitant use and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. NMS has been observed during concurrent use of lithium and antipsychotics.
    Lixisenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
    Lofexidine: (Moderate) Monitor ECG and for hypotension if lofexidine is coadministered with aripiprazole due to the potential for additive QT prolongation and effects on blood pressure. Due to its alpha adrenergic antagonism, aripiprazole has the potential to enhance the effect of lofexidine on blood pressure. Lofexidine may also cause additive sedation with CNS depressants, such as the atypical antipsychotics. Lofexidine prolongs the QT interval, and torsade de pointes (TdP) has been reported during postmarketing use. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
    Lonafarnib: (Major) Reduce the oral aripiprazole dosage by one-half of the usual dose during coadministration of lonafarnib. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor or who are CYP2D6 poor metabolizers. Avoid concurrent use of Aristada Initio and lonafarnib because the dose of Aristada Initio cannot be modified. For other long-active aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with combined strong CYP2D6/CYP3A4 inhibitors; the recommendations are dependent on the aripiprazole IM depot dosage, the product given, and the duration of the concomitant inhibitors as specified in the product labels. Aripiprazole is a substrate for CYP2D6 and CYP3A4; lonafarnib is a strong CYP3A4 inhibitor. Based on simulation studies, a 3-fold increase in aripiprazole exposure is expected when CYP2D6 poor metabolizers are administered a strong CYP3A4 inhibitor. A 4.5-fold increase in aripiprazole exposure is expected when CYP2D6 extensive metabolizers are administered both a strong CYP3A4 and CYP2D6 inhibitor.
    Loop diuretics: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Loperamide: (Moderate) Concomitant use of loperamide and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Lopinavir; Ritonavir: (Major) 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. Patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 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. Adults receiving Abilify Maintena who are PMs and receiving a strong CYP3A4 inhibitor, such as ritonavir, should have a dose reduction to 200 mg/month IM. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1064 mg to 441 mg IM; no dose adjustm