Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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 (90)
- 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.
- 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.
- 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. - brexanolone
brexanolone, cariprazine. Either increases toxicity of the other by 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.
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
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
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.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]
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
Images
Formulary
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.
