cariprazine (Rx)

Brand and Other Names:Vraylar

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 1.5mg
  • 3mg
  • 4.5mg
  • 6mg

Schizophrenia

Treatment of schizophrenia in adults

1.5 mg PO qDay initially; may increase to 3 mg/day on Day 2

Depending upon clinical response and tolerability, further dose adjustments can be made in 1.5 to 3-mg increments; dosing range is 1.5-6 mg PO qDay

Dosages >6 mg/day do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions

Bipolar I Disorder

Manic or mixed episodes

  • Indicated for acute treatment of manic or mixed episodes associated with bipolar I disorder
  • Day 1: 1.5 mg PO
  • Day 2: Increase to 3 mg PO
  • Day 3 and thereafter: Depending on clinical response and tolerability, further dose adjustments can be made in 1.5 to 3-mg increments; dosing range is 3-6 mg PO qDay; not to exceed 6 mg/day

Depressive episodes

  • Indicated for treatment of depressive episodes associated with bipolar I disorder
  • 1.5 mg PO qDay initially
  • Depending upon clinical response and tolerability, dosage can be increased to 3 mg qDay on Day 15; not to exceed 3 mg qDay

Major Depression Disorder

Indicated as adjunctive therapy to antidepressants for treatment of major depressive disorder (MDD)

1.5 mg PO qDay initially

Depending upon clinical response and tolerability, dosage can be increased to 3 mg qDay on Day 15; not to exceed 3 mg qDay

In clinical trials, dosage titration at intervals <14 days resulted in a higher incidence of adverse reactions

Dosage Modifications

Initiating a strong CYP3A4 inhibitor while on stable dose of cariprazine

  • Reduce current cariprazine dose by 50%
  • For patients taking cariprazine 4.5 mg/day, reduce dose to 1.5 mg or 3 mg daily
  • For patients taking 1.5 mg daily, adjust dosing regimen to every other day
  • When the CYP3A4 inhibitor is discontinued, cariprazine dosage may need to be increased

Initiating cariprazine while already on a strong CYP3A4 inhibitor

  • Cariprazine 1.5 mg PO on Days 1 and 3 (no dose on Day 2)
  • From Day 4 onward, administer 1.5 mg PO qDay, then increased to a maximum of 3 mg/day
  • When CYP3A4 inhibitor is discontinued, cariprazine dosage may need to be increased

Coadministration with CYP3A4 inducers

  • Coadministration has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear

Hepatic impairment

  • Mild-to-moderate (Child-Pugh score 5-9): No dosage adjustment required
  • Severe (Child-Pugh score 10-15): Not recommended

Renal impairment

  • Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment required
  • Severe (CrCl <30 mL/min): Not recommended; safety and efficacy has not been established

Dosing Considerations

Following discontinuation of cariprazine, decline in plasma concentrations of active drug and metabolites may not be immediately reflected in patients’ clinical symptoms; plasma concentration of cariprazine and its active metabolites will decline by 50% in ~1 week

Monitor for adverse effects and treatment response for several weeks after initiating the drug and after each dosage change

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and cariprazine

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            Contraindicated (23)

            • amisulpride

              amisulpride, cariprazine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndrome.

            • bosentan

              bosentan will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • carbamazepine

              carbamazepine will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • dabrafenib

              dabrafenib will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • dexamethasone

              dexamethasone will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • efavirenz

              efavirenz will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • enzalutamide

              enzalutamide will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • etravirine

              etravirine will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • mitotane

              mitotane will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • nafcillin

              nafcillin will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • nevirapine

              nevirapine will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • pentobarbital

              pentobarbital will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • phenobarbital

              phenobarbital will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • phenytoin

              phenytoin will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • primidone

              primidone will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • rifabutin

              rifabutin will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • rifampin

              rifampin will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • rifapentine

              rifapentine will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            • St John's Wort

              St John's Wort will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

            Serious - Use Alternative (21)

            • abametapir

              abametapir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • amobarbital

              amobarbital will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, cariprazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ceritinib

              ceritinib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • chloramphenicol

              chloramphenicol will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • hydrocodone

              hydrocodone, cariprazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ivosidenib

              ivosidenib will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • levodopa inhaled

              cariprazine decreases effects of levodopa inhaled by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Atypical (2nd generation) antipsychotics inhibit dopamine D2 receptors in varying degrees (clozapine and quetiapine are lower risk). .

            • lonafarnib

              lonafarnib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • lorlatinib

              lorlatinib will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • metoclopramide intranasal

              cariprazine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

              cariprazine increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.

            • mifepristone

              mifepristone will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong mifepristone initiated, reduce current dosage of cariprazine by half; if patient is already taking the CYP3A4 inhibitor and initiating cariprazine, follow manufacturer?s recommendation

            • olopatadine intranasal

              cariprazine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • safinamide

              cariprazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

            • secobarbital

              secobarbital will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selinexor

              selinexor, cariprazine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

            • sufentanil SL

              sufentanil SL, cariprazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tucatinib

              tucatinib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • voxelotor

              voxelotor will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (101)

            • acrivastine

              acrivastine and cariprazine both increase sedation. Use Caution/Monitor.

            • almotriptan

              almotriptan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • amifostine

              amifostine, cariprazine. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Due to its alpha adrenergic antagonism, atypical antipsychotic agents has the potential to enhance the effect of certain antihypertensive agents. Monitor blood pressure and adjust dose accordingly.

            • amisulpride

              amisulpride and cariprazine both increase sedation. Use Caution/Monitor.

            • asenapine

              asenapine and cariprazine both increase sedation. Use Caution/Monitor.

            • asenapine transdermal

              asenapine transdermal and cariprazine both increase sedation. Use Caution/Monitor.

            • atazanavir

              atazanavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • avapritinib

              avapritinib and cariprazine both increase sedation. Use Caution/Monitor.

            • belzutifan

              belzutifan will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • benazepril

              cariprazine increases toxicity of benazepril by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.

              benazepril increases toxicity of cariprazine by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen and cariprazine both increase sedation. Use Caution/Monitor.

            • brexanolone

              brexanolone, cariprazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • brexpiprazole

              brexpiprazole and cariprazine both increase sedation. Use Caution/Monitor.

            • brimonidine

              brimonidine and cariprazine both increase sedation. Use Caution/Monitor.

            • brivaracetam

              brivaracetam and cariprazine both increase sedation. Use Caution/Monitor.

            • buprenorphine subdermal implant

              buprenorphine subdermal implant and cariprazine both increase sedation. Use Caution/Monitor.

            • buprenorphine transdermal

              buprenorphine transdermal and cariprazine both increase sedation. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              cariprazine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

            • captopril

              cariprazine, captopril. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

            • cenobamate

              cenobamate, cariprazine. Either increases effects of the other by sedation. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • cobicistat

              cobicistat will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • conivaptan

              conivaptan will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • daridorexant

              cariprazine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • darunavir

              darunavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • deutetrabenazine

              cariprazine and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics.

              cariprazine and deutetrabenazine both increase sedation. Use Caution/Monitor.

            • dextromethorphan

              dextromethorphan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • difelikefalin

              difelikefalin and cariprazine both increase sedation. Use Caution/Monitor.

            • dihydroergotamine

              dihydroergotamine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • duvelisib

              duvelisib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. will increase the level or effect of

            • elagolix

              elagolix will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eletriptan

              eletriptan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • encorafenib

              encorafenib, cariprazine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • ergoloid mesylates

              ergoloid mesylates, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • ergotamine

              ergotamine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • esketamine intranasal

              esketamine intranasal, cariprazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • fedratinib

              fedratinib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenfluramine

              cariprazine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.

            • fentanyl

              fentanyl, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • flibanserin

              flibanserin, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • fosamprenavir

              fosamprenavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • frovatriptan

              frovatriptan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • ganaxolone

              cariprazine and ganaxolone both increase sedation. Use Caution/Monitor.

            • grapefruit

              grapefruit will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • idelalisib

              idelalisib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • imatinib

              imatinib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • indinavir

              indinavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • insulin degludec

              cariprazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

            • insulin degludec/insulin aspart

              cariprazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

            • insulin inhaled

              cariprazine decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

            • isoniazid

              isoniazid will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • istradefylline

              istradefylline will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              itraconazole will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • ketoconazole

              ketoconazole will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • lasmiditan

              lasmiditan, cariprazine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant, cariprazine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • lenacapavir

              lenacapavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • levoketoconazole

              levoketoconazole will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • levomilnacipran

              levomilnacipran, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • linezolid

              linezolid, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • lithium

              lithium, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • lopinavir

              lopinavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • lorcaserin

              lorcaserin, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • meperidine

              meperidine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • metformin

              cariprazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

            • methadone

              methadone, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • methylergonovine

              methylergonovine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • methylphenidate

              cariprazine increases toxicity of methylphenidate by pharmacodynamic antagonism. Use Caution/Monitor. Closely monitor for signs of altered clinical response to either methylphenidate or an antipsychotic when using these drugs in combination.

            • midazolam intranasal

              midazolam intranasal, cariprazine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • milnacipran

              milnacipran, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • naratriptan

              naratriptan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • nefazodone

              nefazodone will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • nelfinavir

              nelfinavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • nicardipine

              nicardipine will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • oliceridine

              oliceridine, cariprazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • paroxetine

              paroxetine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • phenelzine

              phenelzine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • posaconazole

              posaconazole will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • procarbazine

              procarbazine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • promethazine

              promethazine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • quinidine

              quinidine will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • remimazolam

              remimazolam, cariprazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • ribociclib

              ribociclib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • rucaparib

              rucaparib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • saquinavir

              saquinavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • selegiline

              selegiline, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases effects of cariprazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases effects of cariprazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

            • stiripentol

              stiripentol, cariprazine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol, cariprazine. Either increases effects of the other by sedation. Use Caution/Monitor. Concurrent use of medications with CNS depressant effects together with thalidomide should be avoided due to the risk for additive sedative effects.

            • sumatriptan

              sumatriptan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • sumatriptan intranasal

              sumatriptan intranasal, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • tazemetostat

              tazemetostat will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • tipranavir

              tipranavir will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • tranylcypromine

              tranylcypromine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • venlafaxine

              venlafaxine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • vilazodone

              vilazodone, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • voriconazole

              voriconazole will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

            • zolmitriptan

              zolmitriptan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            Minor (4)

            • acetazolamide

              acetazolamide will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • anastrozole

              anastrozole will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • larotrectinib

              larotrectinib will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Schizophrenia

            • Extrapyramidal symptoms, all (24-33%)
            • Extrapyramidal symptoms, excluding akathisia/restlessness (15-20%)
            • Parkinsonism (13-18%)
            • Headache (9-18%)
            • Akathisia (9-14%)
            • Insomnia (11-13%)

            Bipolar mania

            • Extrapyramidal symptoms, all (41-45%)
            • Extrapyramidal symptoms, excluding akathisia/restlessness (26-29%)
            • Parkinsonism (21-26%)
            • Akathisia (20-21%)
            • Headache (13-14%)
            • Nausea (11-13%)
            • Constipation (6-11%)

            Bipolar depression

            • Extrapyramidal symptoms, all (10-19%)

            MDD (cariprazine and antidepressant therapy)

            • Akathisia (7-23%)
            • Extrapyramidal symptoms (5-18%)
            • Insomnia (14-16%)
            • Nausea (7-13%)
            • Somnolence (5-11%)

            1-10%

            Decreased appetite (>1%)

            Schizophrenia

            • Constipation (6-10%)
            • Somnolence (5-10%)
            • Nausea (5-8%)
            • Abdominal pain (3-7%)
            • Restlessness (4-6%)
            • Anxiety (3-6%)
            • Toothache (3-6%)
            • Hypertension (2-7%)
            • Dyspepsia (4-5%)
            • Vomiting (4-5%)
            • Dizziness (3-5%)
            • Agitation (3-5%)
            • Diarrhea (1-5%)
            • Pain in extremity (2-4%)
            • Cough (1-4%)
            • Tachycardia (2-3%)
            • Increased weight (2-3%)
            • Decreased appetite (1-3%)
            • Dry mouth (1-3%)
            • Fatigue (1-3%)
            • Increased CPK (1-3%)
            • Musculoskeletal stiffness (<3%)
            • Back pain (1-3%)
            • Dystonia (2%)
            • Tachycardia (1-2%)
            • Arthralgia (1-2%)
            • Hepatic enzyme increased (1-2%)
            • Nasopharyngitis (1-2%)
            • Urinary tract infections (1-2%)
            • Rash (1-2%)

            Bipolar mania

            • Vomiting (8-10%)
            • Insomnia (8-9%)
            • Dyspepsia (7-9%)
            • Somnolence (7-8%)
            • Abdominal pain (6-8%)
            • Restlessness (7%)
            • Dizziness (6-7%)
            • Diarrhea (5-6%)
            • Hypertension (4-5%)
            • Fatigue (4-5%)
            • Dystonia (3-5%)
            • Blurred vision (4%)
            • Decreased appetite (3-4%)
            • Toothache (3-4%)
            • Pain in extremity (2-4%)
            • Pyrexia (1-4%)
            • Weight increased (2-3%)
            • Increased CPK (2-3%)
            • Dry mouth (2-3%)
            • Oropharyngeal pain (1-3%)
            • Back pain (1-3%)
            • Hepatic enzymes increased (1-3%)
            • Musculoskeletal stiffness (2%)
            • Tachycardia (1-2%)

            Bipolar depression

            • Insomnia (7-10%)
            • Akathisia (6-10%)
            • Nausea (7%)
            • Somnolence (6-7%)
            • Restlessness (2-7%)
            • Extrapyramidal symptoms, excluding akathisia/restlessness (4-6%)
            • Dizziness (3-4%)
            • Fatigue (3-4%)
            • Parkinsonism (3-4%)
            • Increased appetite (3%)
            • Increased weight (2%)
            • Musculoskeletal stiffness (≤1%)

            MDD (cariprazine and antidepressant therapy)

            • Fatigue (3-10%)
            • Insomnia (9-10%)
            • Restlessness (4-8%)
            • Nausea (6-7%)
            • Dizziness (4-5%)
            • Dry mouth (3-5%)
            • Constipation (2-5%)
            • Increased appetite (2-5%)
            • Blurred vision (1-4%)
            • Nasopharyngitis (1-4%)
            • Agitation (<3%)
            • Weight increased (2-3%)
            • Back pain (2-3%)
            • Vomiting (1-3%)
            • Anxiety (1-3%)
            • Blurred vision (<2%)
            • Palpitations (<2%)
            • Hyperhidrosis (1-2%)
            • Edema (1-2%)
            • Myalgia (1-2%)

            <1%

            Gastroesophageal reflux disease (0.1-1%)

            Gastritis (0.1-1%)

            Suicide attempts (0.1-1%)

            Suicide ideation (0.1-1%)

            Hyponatremia (0.1-1%)

            Pollakiuria (0.1-1%)

            Hyperhidrosis (0.1-1%)

            Rhabdomyolysis (0.1%)

            Ischemic stroke (0.1%)

            Completed suicide (0.1%)

            Hepatitis (0.1%)

            Bipolar disorder

            • Tardive dyskinesia (<1%)
            • Dystonia (<1%)

            Postmarketing Reports

            Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome

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            Warnings

            Black Box Warnings

            Increased mortality in elderly patients with dementia-related psychosis

            • Elderly patients with dementia-related psychosis treatment with antipsychotic drugs are at an increased risk of death
            • Not approved for treatment of patients with dementia-related psychosis

            Suicidal thoughts and behaviors

            • Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies
            • Closely monitor all antidepressant-treated patients for clinical worsening, and for the emergence of suicidal thoughts and behaviors
            • Safety and effectiveness of cariprazine has not been established in pediatric patients

            Contraindications

            Hypersensitivity to cariprazine

            Cautions

            Antipsychotic drugs increase the all-cause risk of death in elderly patients with dementia-related psychosis; a higher incidence of stroke and TIA, including fatal stroke, was also observed (see Black Box Warnings)

            Hypersensitivity reactions reported ranging fom rash, pruritus, urticaria, and events suggestive of angioedema (eg, swollen, tongue, lip swelling, face edema, pharyngeal edema, facial swelling)

            Neuroleptic malignant syndrome reported; monitor for hyperpyrexia, muscle rigidity, delirium, and autonomic instability; other signs include increased CPK, myoglobinuria (rhabdomyolysis), and acute renal failure; if NMS is suspected, immediately discontinue treatment

            Tardive dyskinesia, a potentially irreversible, involuntary, dyskinetic movement syndrome, may develop in patients treated with antipsychotics

            Adverse effects may first appear several weeks after initiating treatment, as drug and metabolite levels accumulate; monitor for extrapyramidal symptoms or akathisia

            Leukopenia and neutropenia reported; agranulocytosis (including fatal cases) reported with other atypical antipsychotics; discontinue cariprazine in patients with absolute neutrophil count <1000/mm³ and follow WBC until recovery

            May cause orthostatic hypotension and syncope; caution in patients vulnerable to hypotension (eg, elderly, dehydration, hypovolemia, concomitant antihypertensive drugs, cardiovascular or cerebrovascular disease)

            May cause seizures; risk is greatest with history of seizures or conditions that lower seizure threshold

            Body temperature dysregulation reported; may disrupt ability to reduce core body temperature; caution with strenuous exercise, exposure to extreme heat, dehydration, and coadministration with anticholinergic medications

            Esophageal dysmotility and aspiration reported with antipsychotic drug use

            May cause somnolence with potential to impair judgment or thinking; may cause postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; for patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy

            Drug interactions overview

            • Coadministration with a strong CYP3A4 inhibitor increases the exposures of cariprazine and its major active metabolite, didesmethylcariprazine (DDCAR), compared to use of cariprazine alone (see Dosage Modifications)
            • Effect of CYP3A4 inducers on the exposure of cariprazine has not been evaluated, and net effect is unclear

            Metabolic changes

            • Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, reported; assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically
            • Lipids alteration has occurred; obtain a fasting lipid profile at baseline and monitor periodically during treatment before or soon after initiation of antipsychotic medication
            • Weight gain observed; monitor weight at baseline and frequently thereafter

            Suicidal thoughts or behaviors

            • Pooled analyses of placebo-controlled trials of antidepressive drugs showed an increased risk of suicidal thoughts or behavior in patients aged ≤24 yr taking these drugs for any indication; monitor for emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
            • Inform patients, their caregivers, and families of the increase the risk of suicidal thoughts and behavior; advise to be alert for the emergence or worsening of signs and symptoms
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            Pregnancy

            Pregnancy

            Neonates exposed to antipsychotic drugs during third trimester of pregnancy are at risk for extrapyramidal symptoms or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU support and prolonged hospitalization

            Pregnancy exposure registry

            • Report exposure during pregnancy to the National Pregnancy Registry for Atypical Antipsychotics 1-866-961-2388 OR, http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/

            Animal data

            • Administration in pregnant rats during organogenesis at doses 0.2 to 3.5 times maximum recommended human dose caused fetal developmental toxicity at all doses, including reduced body weight, decreased male anogenital distance, and skeletal malformations of bent limb bones, scapula, and humerus
            • Decreased postnatal survival, birth weight, and post-weaning body weight was also observed

            Lactation

            Unknown if distributed in human breast milk

            Present in rat milk

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Precise mechanism by which cariprazine works for schizophrenia or bipolar disorder is unknown

            Efficacy could be mediated through a combination of partial agonist activity at central dopamine (D2) and serotonin 5-HT1A receptors

            Forms 2 major metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), that have in vitro receptor binding profiles similar to the parent drug

            Absorption

            Peak plasma time: 3-6 hr (cariprazine)

            Mean concentrations of DCAR and DDCAR are ~30% and 400%, respectively, of cariprazine concentrations by the end of 12-week treatment

            Distribution

            Protein bound: 91-97% (parent drug and metabolites)

            Metabolism

            Active metabolites: Desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR) are pharmacologically equipotent to cariprazine

            Extensively metabolized by CYP3A4 to DCAR and DDCAR

            Metabolized to a lesser extent by CYP2D6 to DCAR and DDCAR

            DDCAR is metabolized by CYP3A4 to a hydroxylated metabolite

            Elimination

            Half-life: 2-4 days (cariprazine); 1-3 weeks (DDCAR)

            Excretion, cariprazine 12.5 mg/day: Urine (21%); [1.2% unchanged]

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            Administration

            Instructions

            Take orally with or without food

            Discontinuation

            • Decline in plasma concentrations of active drug and metabolites may not be immediately reflected in patients’ clinical symptoms
            • Plasma concentration declines by 50% in ~1 week
            • There are no systematically collected data to address switching patients from cariprazine to other antipsychotics or concomitant administration with other antipsychotics

            Storage

            Store at controlled room temperature (20-25ºC [68-77ºF]); excursions permitted between 15-30ºC (59-86ºF)

            Protect 3- and 4.5-mg capsules from light to prevent potential color fading

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.