brexpiprazole (Rx)

Schizophrenia

Indicated for treatment of schizophrenia

Days 1-4: 1 mg PO qDay

Day 5-7: Titrate to 2 mg qDay

Day 8: Titrate to 4 mg/day based on the patient’s clinical response and tolerability

Target dose: 2-4 mg PO qDay; not to exceed 4 mg/day

Periodically reassess to determine the continued need and appropriate dose

Depression

Indicated an adjunctive therapy to antidepressants for major depressive disorder (MDD)

0.5 mg or 1 mg PO qDay initially

Titrate according to clinical response and tolerability in weekly intervals to 1 mg/day and then up to 2 mg/day; not to exceed 3 mg/day

Periodically reassess to determine the continued need and appropriate dose

Agitation Associated With Alzheimer Dementia

Indicated for agitation associated with dementia due to Alzheimer disease

Days 1-7: 0.5 mg PO qDay

Days 8-14: Increase to 1 mg PO qDay

Days 15: Increase to 2 mg PO qDay

Target dose: 2 mg PO qDay

May increase to maximum recommended dosage of 3 mg qDay after at least 14 days, based on clinical response and tolerability

Dosage Modifications

Renal impairment

• Moderate, severe, or end-stage renal disease (ESRD) (CrCl <60 mL/min)

  • MDD or agitation associated with Alzheimer dementia: Not to exceed 2 mg/day
  • Schizophrenia: Not to exceed 3 mg/day

Hepatic impairment

• Moderate-to-severe hepatic impairment (Child-Pugh ≥7)

  • MDD or agitation associated with Alzheimer dementia: Not to exceed 2 mg/day
  • Schizophrenia: Not to exceed 3 mg/day

CYP2D6 poor metabolizers

• CYP2D6 poor metabolizers: Administer half of the usual brexpiprazole dose
• Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors: Administer a quarter of the usual brexpiprazole dose

CYP2D6 or CYP3A4 inhibitors

• Strong CYP2D6 inhibitors: Administer half of the usual brexpiprazole dose (see note below for MDD)
• Strong CYP3A4 inhibitors: Administer half of the usual brexpiprazole dose
• Strong/moderate CYP2D6 inhibitors plus strong/moderate CYP3A4 inhibitors: Administer a quarter of the usual brexpiprazole dose
• If the coadministered drug is discontinued, adjust the brexpiprazole dosage to its original level
• NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD

CYP3A4 inducers

• Strong CYP3A4 inducers: Double usual dose over 1 to 2 weeks
• If the coadministered CYP3A4 inducer is discontinued, reduce the brexpiprazole dosage to the original level over 1-2 weeks

Geriatric Dosage & Uses

Antipsychotic drugs increase the risk of death in elderly patients with dementia-related psychosis

Brexpiprazole is not approved for the treatment of patients with dementia-related psychosis (see Black Box Warnings)

Limitations of use: Not indicated as an as needed (PRN) treatment for agitation associated with dementia due to Alzheimer disease

Schizophrenia

Indicated for treatment of schizophrenia in adults and pediatric patients aged ≥13 years

<13 years: Safety and efficacy not established

13-17 years

• Days 1-4: 0.5 mg PO qDay
• Days 5-7: Titrate to 1 mg PO qDay
• Day 8: 2 mg PO qDay based on clinical response and tolerability
• Target dose: 2-4 mg PO qDay; weekly 1-mg dose increments can be made, not to exceed 4 mg/day
• Periodically reassess to determine continued need and appropriate dose

Dosage Modifications

Renal impairment

• Moderate, severe, or end-stage renal disease (ESRD) (CrCl <60 mL/min)
• MDD: Not to exceed 2 mg/day
• Schizophrenia: Not to exceed 3 mg/day

Hepatic impairment

• Moderate-to-severe hepatic impairment (Child-Pugh ≥7) H5
• MDD: Not to exceed 2 mg/day
• Schizophrenia: Not to exceed 3 mg/day

CYP2D6 poor metabolizers

• CYP2D6 poor metabolizers: Administer half of the usual brexpiprazole dose
• CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors: Administer a quarter of the usual brexpiprazole dose

CYP2D6 or CYP3A4 inhibitors

• Strong CYP2D6 inhibitors: Administer half of the usual brexpiprazole dose
• Strong CYP3A4 inhibitors: Administer half of the usual brexpiprazole dose
• Strong/moderate CYP2D6 inhibitors plus strong/moderate CYP3A4 inhibitors: Administer a quarter of the usual brexpiprazole dose
• If the coadministered drug is discontinued, adjust the brexpiprazole dosage to its original level
• NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD

CYP3A4 inducers

• Strong CYP3A4 inducers: Double usual dose over 1-2 weeks
• If coadministered CYP3A4 inducer is discontinued, reduce brexpiprazole dosage to the original level over 1-2 weeks

Antipsychotic drugs increase the risk of death in elderly patients with dementia-related psychosis

Brexpiprazole is not approved for the treatment of patients with dementia-related psychosis

Contraindicated (2)

• amisulpride

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

• thalidomide

  brexpiprazole and thalidomide both increase sedation. Contraindicated.

Serious - Use Alternative (34)

• alfentanil

  brexpiprazole and alfentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• apalutamide

  apalutamide will decrease the level or effect of brexpiprazole 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 and brexpiprazole both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine

  brexpiprazole and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine buccal

  brexpiprazole and buprenorphine buccal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine subdermal implant

  brexpiprazole and buprenorphine subdermal implant both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine subdermal implant and brexpiprazole both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  brexpiprazole and buprenorphine transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  brexpiprazole and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• butalbital

  brexpiprazole and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• chloramphenicol

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

• dacomitinib

  dacomitinib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• fentanyl

  brexpiprazole and fentanyl both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl intranasal

  brexpiprazole and fentanyl intranasal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl intranasal and brexpiprazole both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl iontophoretic transdermal system

  brexpiprazole and fentanyl iontophoretic transdermal system both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transdermal

  brexpiprazole and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transmucosal

  brexpiprazole and fentanyl transmucosal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fexinidazole

  fexinidazole will increase the level or effect of brexpiprazole 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.

• givosiran

  givosiran will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• hydrocodone

  brexpiprazole and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• hydromorphone

  brexpiprazole and hydromorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• ivosidenib

  ivosidenib will decrease the level or effect of brexpiprazole 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.

• lonafarnib

  lonafarnib will increase the level or effect of brexpiprazole 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.

• methadone

  brexpiprazole and methadone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• metoclopramide intranasal

  brexpiprazole, 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.

• morphine

  brexpiprazole and morphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• nelfinavir

  nelfinavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• olopatadine intranasal

  brexpiprazole 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.

• oxycodone

  brexpiprazole and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• oxymorphone

  brexpiprazole and oxymorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• remifentanil

  brexpiprazole and remifentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• secobarbital

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

• selinexor

  selinexor, brexpiprazole. 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.

• tucatinib

  tucatinib will increase the level or effect of brexpiprazole 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 brexpiprazole 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 (271)

• acetaminophen/phenyltoloxamine

  brexpiprazole and acetaminophen/phenyltoloxamine both increase sedation. Use Caution/Monitor.

• acrivastine

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

• alprazolam

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

• amifostine

  amifostine, brexpiprazole. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Monitor blood pressure and adjust dose accordingly.

• amiodarone

  amiodarone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  amiodarone will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• amisulpride

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

• amitriptyline

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

• amobarbital

  amobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  brexpiprazole and amobarbital both increase sedation. Use Caution/Monitor.

• amoxapine

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

• aprepitant

  aprepitant will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• aripiprazole

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

• asenapine

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

• asenapine transdermal

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

• atazanavir

  atazanavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• avapritinib

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

• baclofen

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

• belzutifan

  belzutifan will decrease the level or effect of brexpiprazole 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

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

• bicalutamide

  bicalutamide will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• bortezomib

  bortezomib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• bosentan

  bosentan will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• brexanolone

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

• brimonidine

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

• brivaracetam

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

• brompheniramine

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

• bupropion

  bupropion will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• butabarbital

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

• butorphanol

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

• captopril

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

• carbamazepine

  carbamazepine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• carbinoxamine

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

• cariprazine

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

• carisoprodol

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

• cenobamate

  cenobamate will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
  
  cenobamate, brexpiprazole. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  ceritinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• cetirizine

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

• chlordiazepoxide

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

• chloroquine

  chloroquine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• chlorpheniramine

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

• chlorpromazine

  chlorpromazine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.
  
  brexpiprazole and chlorpromazine both increase sedation. Use Caution/Monitor.

• chlorzoxazone

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

• cimetidine

  cimetidine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  cimetidine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• cinacalcet

  cinacalcet will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• clarithromycin

  clarithromycin will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• clemastine

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

• clobazam

  clobazam will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and clobazam both increase sedation. Use Caution/Monitor.

• clomipramine

  clomipramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and clomipramine both increase sedation. Use Caution/Monitor.

• clonazepam

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

• clonidine

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

• clorazepate

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

• clozapine

  clozapine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and clozapine both increase sedation. Use Caution/Monitor.

• cobicistat

  cobicistat will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  cobicistat will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• cocaine topical

  cocaine topical will decrease the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• codeine

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

• conivaptan

  conivaptan will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• crizotinib

  crizotinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• cyclobenzaprine

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

• cyclosporine

  cyclosporine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• cyproheptadine

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

• dabrafenib

  dabrafenib will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• dantrolene

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

• daridorexant

  brexpiprazole 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.

• darifenacin

  darifenacin will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• darunavir

  darunavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• desflurane

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

• desipramine

  desipramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and desipramine both increase sedation. Use Caution/Monitor.

• deutetrabenazine

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

• dexamethasone

  dexamethasone will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• dexbrompheniramine

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

• dexchlorpheniramine

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

• dexmedetomidine

  dexmedetomidine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• diazepam

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

• diazepam intranasal

  diazepam intranasal, brexpiprazole. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• difelikefalin

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

• difenoxin hcl

  brexpiprazole and difenoxin hcl both increase sedation. Use Caution/Monitor.

• diltiazem

  diltiazem will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• dimenhydrinate

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

• diphenhydramine

  diphenhydramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and diphenhydramine both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  brexpiprazole and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• disulfiram

  disulfiram will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• doxepin

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

• doxycycline

  doxycycline will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• doxylamine

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

• dronedarone

  dronedarone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  dronedarone will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• droperidol

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

• duloxetine

  duloxetine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• duvelisib

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

• efavirenz

  efavirenz will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.
  
  brexpiprazole and efavirenz both increase sedation. Use Caution/Monitor.

• elagolix

  elagolix will decrease the level or effect of brexpiprazole 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.

• eliglustat

  eliglustat will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• encorafenib

  encorafenib, brexpiprazole. 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.

• entacapone

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

• enzalutamide

  enzalutamide will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• erythromycin base

  erythromycin base will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• esketamine intranasal

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

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• estazolam

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

• eszopiclone

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

• ethanol

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

• ethosuximide

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

• ethotoin

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

• etravirine

  etravirine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• fedratinib

  fedratinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
  
  fedratinib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• felbamate

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

• fenfluramine

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

• fexofenadine

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

• flibanserin

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

• fluconazole

  fluconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• fluoxetine

  fluoxetine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• fluphenazine

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

• flurazepam

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

• fosamprenavir

  fosamprenavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• fosaprepitant

  fosaprepitant will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• fosphenytoin

  fosphenytoin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• gabapentin

  gabapentin, brexpiprazole. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
  
  brexpiprazole and gabapentin both increase sedation. Use Caution/Monitor.

• gabapentin enacarbil

  gabapentin enacarbil, brexpiprazole. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• ganaxolone

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

• grapefruit

  grapefruit will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• guanfacine

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

• haloperidol

  haloperidol will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  haloperidol will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.
  
  brexpiprazole and haloperidol both increase sedation. Use Caution/Monitor.

• hydroxyzine

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

• idelalisib

  idelalisib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• iloperidone

  iloperidone will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.
  
  brexpiprazole and iloperidone both increase sedation. Use Caution/Monitor.

• imatinib

  imatinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  imatinib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• imipramine

  imipramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and imipramine both increase sedation. Use Caution/Monitor.

• indinavir

  indinavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• isoflurane

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

• isoniazid

  isoniazid will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  isoniazid will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• istradefylline

  istradefylline will increase the level or effect of brexpiprazole 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 brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• ketamine

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

• ketoconazole

  ketoconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  ketoconazole will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• ketotifen, drug-eluting contact lens

  brexpiprazole and ketotifen, drug-eluting contact lens both increase sedation. Use Caution/Monitor.

• lamotrigine

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

• lapatinib

  lapatinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• lasmiditan

  lasmiditan, brexpiprazole. 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, brexpiprazole. 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 brexpiprazole 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.

• levetiracetam

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

• levocetirizine

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

• levoketoconazole

  levoketoconazole will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  levoketoconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• levorphanol

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

• lidocaine

  lidocaine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  lidocaine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• lopinavir

  lopinavir will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.
  
  lopinavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• loratadine

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

• lorazepam

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

• lorcaserin

  lorcaserin will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• lorlatinib

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

• loxapine

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

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• lumateperone

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

• lurasidone

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

• maprotiline

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

• meclizine

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

• meperidine

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

• meprobamate

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

• metaxalone

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

• metformin

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

• methadone

  methadone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• methimazole

  methimazole will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• methocarbamol

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

• methohexital

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

• methsuximide

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

• metronidazole

  metronidazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• midazolam

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

• midazolam intranasal

  midazolam intranasal, brexpiprazole. 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.

• mifepristone

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

• mirtazapine

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

• mitotane

  mitotane will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• molindone

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

• nafcillin

  nafcillin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• nalbuphine

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

• nefazodone

  nefazodone will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  nefazodone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• netupitant/palonosetron

  netupitant/palonosetron will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• nevirapine

  nevirapine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• nicardipine

  nicardipine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  nicardipine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• nitrous oxide

  brexpiprazole and nitrous oxide both increase sedation. Use Caution/Monitor.

• nortriptyline

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

• olanzapine

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

• oliceridine

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

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.
  
  ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• opicapone

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

• opium tincture

  brexpiprazole and opium tincture both increase sedation. Use Caution/Monitor.

• orphenadrine

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

• oxazepam

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

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• paliperidone

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

• panobinostat

  panobinostat will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• paroxetine

  paroxetine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• pentazocine

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

• pentobarbital

  pentobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.
  
  brexpiprazole and pentobarbital both increase sedation. Use Caution/Monitor.

• perampanel

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

• perphenazine

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

• pheniramine

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

• phenobarbital

  phenobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.
  
  brexpiprazole and phenobarbital both increase sedation. Use Caution/Monitor.

• phenytoin

  phenytoin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• pimozide

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

• pomalidomide

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

• posaconazole

  posaconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• pregabalin

  pregabalin, brexpiprazole. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
  
  brexpiprazole and pregabalin both increase sedation. Use Caution/Monitor.

• primidone

  primidone will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.
  
  brexpiprazole and primidone both increase sedation. Use Caution/Monitor.

• prochlorperazine

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

• promethazine

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

• propofol

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

• protriptyline

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

• pyrilamine

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

• pyrimethamine

  pyrimethamine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• quazepam

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

• quetiapine

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

• quinidine

  quinidine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.
  
  quinidine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• quinine

  quinine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• ramelteon

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

• ranolazine

  ranolazine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• remimazolam

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

• reserpine

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

• ribociclib

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

• rifabutin

  rifabutin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• rifampin

  rifampin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• rifapentine

  rifapentine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• risperidone

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

• ritonavir

  ritonavir will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.
  
  ritonavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• rolapitant

  rolapitant will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• rucaparib

  rucaparib will increase the level or effect of brexpiprazole 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 brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• schisandra

  schisandra will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• scopolamine

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

• sertraline

  sertraline will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  sertraline will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• sevoflurane

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

• sodium oxybate

  brexpiprazole and sodium oxybate both increase sedation. Use Caution/Monitor.

• St John's Wort

  St John's Wort will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• stiripentol

  stiripentol, brexpiprazole. 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.

• sufentanil

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

• sufentanil SL

  brexpiprazole and sufentanil SL both increase sedation. Use Caution/Monitor.

• suvorexant

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

• tapentadol

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

• tasimelteon

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

• tazemetostat

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

• tecovirimat

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

• temazepam

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

• terbinafine

  terbinafine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• tetrabenazine

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

• tetracycline

  tetracycline will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• thioridazine

  thioridazine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and thioridazine both increase sedation. Use Caution/Monitor.

• thiothixene

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

• tiagabine

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

• ticagrelor

  ticagrelor will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• ticlopidine

  ticlopidine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• tipranavir

  tipranavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• tizanidine

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

• tolcapone

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

• topiramate

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

• tramadol

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

• tranylcypromine

  tranylcypromine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• trazodone

  trazodone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and trazodone both increase sedation. Use Caution/Monitor.

• triazolam

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

• trifluoperazine

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

• triprolidine

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

• valproic acid

  brexpiprazole and valproic acid both increase sedation. Use Caution/Monitor.

• verapamil

  verapamil will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• vigabatrin

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

• voriconazole

  voriconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• zaleplon

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

• ziconotide

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

• zileuton

  zileuton will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• ziprasidone

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

• zolpidem

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

• zonisamide

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

Minor (4)

• acetazolamide

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

• anastrozole

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

• cyclophosphamide

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

• larotrectinib

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

• acetaminophen/phenyltoloxamine

  Monitor Closely (1)brexpiprazole and acetaminophen/phenyltoloxamine both increase sedation. Use Caution/Monitor.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acrivastine

  Monitor Closely (1)acrivastine and brexpiprazole both increase sedation. Use Caution/Monitor.

• alfentanil

  Serious - Use Alternative (1)brexpiprazole and alfentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• alprazolam

  Monitor Closely (1)brexpiprazole and alprazolam both increase sedation. Use Caution/Monitor.

• amifostine

  Monitor Closely (1)amifostine, brexpiprazole. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Monitor blood pressure and adjust dose accordingly.

• amiodarone

  Monitor Closely (2)amiodarone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  amiodarone will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• amisulpride

  Contraindicated (1)amisulpride, brexpiprazole. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndrome.Monitor Closely (1)amisulpride and brexpiprazole both increase sedation. Use Caution/Monitor.

• amitriptyline

  Monitor Closely (1)brexpiprazole and amitriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

  Monitor Closely (2)amobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  brexpiprazole and amobarbital both increase sedation. Use Caution/Monitor.

• amoxapine

  Monitor Closely (1)brexpiprazole and amoxapine both increase sedation. Use Caution/Monitor.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of brexpiprazole 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.

• aprepitant

  Monitor Closely (1)aprepitant will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• aripiprazole

  Monitor Closely (1)brexpiprazole and aripiprazole both increase sedation. Use Caution/Monitor.

• asenapine

  Monitor Closely (1)asenapine and brexpiprazole both increase sedation. Use Caution/Monitor.

• asenapine transdermal

  Monitor Closely (1)asenapine transdermal and brexpiprazole both increase sedation. Use Caution/Monitor.

• atazanavir

  Monitor Closely (1)atazanavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• avapritinib

  Monitor Closely (1)avapritinib and brexpiprazole both increase sedation. Use Caution/Monitor.

• baclofen

  Monitor Closely (1)brexpiprazole and baclofen both increase sedation. Use Caution/Monitor.

• belzutifan

  Monitor Closely (1)belzutifan will decrease the level or effect of brexpiprazole 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

  Monitor Closely (1)brexpiprazole increases toxicity of benazepril by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (1)benzhydrocodone/acetaminophen and brexpiprazole both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bicalutamide

  Monitor Closely (1)bicalutamide will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• bortezomib

  Monitor Closely (1)bortezomib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• bosentan

  Monitor Closely (1)bosentan will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• brexanolone

  Monitor Closely (1)brexanolone, brexpiprazole. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brimonidine

  Monitor Closely (2)brimonidine and brexpiprazole both increase sedation. Use Caution/Monitor.
  
  brexpiprazole and brimonidine both increase sedation. Use Caution/Monitor.

• brivaracetam

  Monitor Closely (1)brexpiprazole and brivaracetam both increase sedation. Use Caution/Monitor.

• brompheniramine

  Monitor Closely (1)brexpiprazole and brompheniramine both increase sedation. Use Caution/Monitor.

• buprenorphine

  Serious - Use Alternative (1)brexpiprazole and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine buccal

  Serious - Use Alternative (1)brexpiprazole and buprenorphine buccal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine subdermal implant

  Serious - Use Alternative (2)brexpiprazole and buprenorphine subdermal implant both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine subdermal implant and brexpiprazole both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  Serious - Use Alternative (1)brexpiprazole and buprenorphine transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Serious - Use Alternative (1)brexpiprazole and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bupropion

  Monitor Closely (1)bupropion will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• butabarbital

  Monitor Closely (1)brexpiprazole and butabarbital both increase sedation. Use Caution/Monitor.

• butalbital

  Serious - Use Alternative (1)brexpiprazole and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• butorphanol

  Monitor Closely (1)brexpiprazole and butorphanol both increase sedation. Use Caution/Monitor.

• captopril

  Monitor Closely (1)brexpiprazole, captopril. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

• carbamazepine

  Monitor Closely (1)carbamazepine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• carbinoxamine

  Monitor Closely (1)brexpiprazole and carbinoxamine both increase sedation. Use Caution/Monitor.

• cariprazine

  Monitor Closely (1)brexpiprazole and cariprazine both increase sedation. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (1)brexpiprazole and carisoprodol both increase sedation. Use Caution/Monitor.

• cenobamate

  Monitor Closely (2)cenobamate, brexpiprazole. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  Monitor Closely (1)ceritinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• cetirizine

  Monitor Closely (1)brexpiprazole and cetirizine both increase sedation. Use Caution/Monitor.

• chloramphenicol

  Serious - Use Alternative (1)chloramphenicol will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• chlordiazepoxide

  Monitor Closely (1)brexpiprazole and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• chloroquine

  Monitor Closely (1)chloroquine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• chlorpheniramine

  Monitor Closely (1)brexpiprazole and chlorpheniramine both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (2)brexpiprazole and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• chlorzoxazone

  Monitor Closely (1)brexpiprazole and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cimetidine

  Monitor Closely (2)cimetidine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  cimetidine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• cinacalcet

  Monitor Closely (1)cinacalcet will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• clarithromycin

  Monitor Closely (1)clarithromycin will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• clemastine

  Monitor Closely (1)brexpiprazole and clemastine both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (2)brexpiprazole and clobazam both increase sedation. Use Caution/Monitor.
  
  clobazam will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• clomipramine

  Monitor Closely (2)brexpiprazole and clomipramine both increase sedation. Use Caution/Monitor.
  
  clomipramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• clonazepam

  Monitor Closely (1)brexpiprazole and clonazepam both increase sedation. Use Caution/Monitor.

• clonidine

  Monitor Closely (1)brexpiprazole and clonidine both increase sedation. Use Caution/Monitor.

• clorazepate

  Monitor Closely (1)brexpiprazole and clorazepate both increase sedation. Use Caution/Monitor.

• clozapine

  Monitor Closely (2)clozapine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and clozapine both increase sedation. Use Caution/Monitor.

• cobicistat

  Monitor Closely (2)cobicistat will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  cobicistat will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• cocaine topical

  Monitor Closely (1)cocaine topical will decrease the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• codeine

  Monitor Closely (1)brexpiprazole and codeine both increase sedation. Use Caution/Monitor.

• conivaptan

  Monitor Closely (1)conivaptan will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• crizotinib

  Monitor Closely (1)crizotinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• cyclobenzaprine

  Monitor Closely (1)brexpiprazole and cyclobenzaprine both increase sedation. Use Caution/Monitor.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (1)cyclosporine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• cyproheptadine

  Monitor Closely (1)brexpiprazole and cyproheptadine both increase sedation. Use Caution/Monitor.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• dacomitinib

  Serious - Use Alternative (1)dacomitinib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• dantrolene

  Monitor Closely (1)brexpiprazole and dantrolene both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (1)brexpiprazole 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.

• darifenacin

  Monitor Closely (1)darifenacin will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• darunavir

  Monitor Closely (1)darunavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• desflurane

  Monitor Closely (1)brexpiprazole and desflurane both increase sedation. Use Caution/Monitor.

• desipramine

  Monitor Closely (2)desipramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and desipramine both increase sedation. Use Caution/Monitor.

• deutetrabenazine

  Monitor Closely (1)brexpiprazole and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexamethasone

  Monitor Closely (1)dexamethasone will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• dexbrompheniramine

  Monitor Closely (1)brexpiprazole and dexbrompheniramine both increase sedation. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (1)brexpiprazole and dexchlorpheniramine both increase sedation. Use Caution/Monitor.

• dexmedetomidine

  Monitor Closely (1)dexmedetomidine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• diazepam

  Monitor Closely (1)brexpiprazole and diazepam both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (1)diazepam intranasal, brexpiprazole. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• difelikefalin

  Monitor Closely (1)difelikefalin and brexpiprazole both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (1)brexpiprazole and difenoxin hcl both increase sedation. Use Caution/Monitor.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• dimenhydrinate

  Monitor Closely (1)brexpiprazole and dimenhydrinate both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (2)diphenhydramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and diphenhydramine both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (1)brexpiprazole and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• disulfiram

  Monitor Closely (1)disulfiram will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• doxepin

  Monitor Closely (1)brexpiprazole and doxepin both increase sedation. Use Caution/Monitor.

• doxycycline

  Monitor Closely (1)doxycycline will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• doxylamine

  Monitor Closely (1)brexpiprazole and doxylamine both increase sedation. Use Caution/Monitor.

• dronedarone

  Monitor Closely (2)dronedarone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  dronedarone will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• droperidol

  Monitor Closely (1)brexpiprazole and droperidol both increase sedation. Use Caution/Monitor.

• duloxetine

  Monitor Closely (1)duloxetine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• duvelisib

  Monitor Closely (1)duvelisib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. will increase the level or effect of

• efavirenz

  Monitor Closely (2)efavirenz will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.
  
  brexpiprazole and efavirenz both increase sedation. Use Caution/Monitor.

• elagolix

  Monitor Closely (1)elagolix will decrease the level or effect of brexpiprazole 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.

• eliglustat

  Monitor Closely (1)eliglustat will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• encorafenib

  Monitor Closely (1)encorafenib, brexpiprazole. 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.

• entacapone

  Monitor Closely (1)brexpiprazole and entacapone both increase sedation. Use Caution/Monitor.

• enzalutamide

  Monitor Closely (1)enzalutamide will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• erythromycin base

  Monitor Closely (1)erythromycin base will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• erythromycin ethylsuccinate

  Monitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• erythromycin stearate

  Monitor Closely (1)erythromycin stearate will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, brexpiprazole. Either increases levels of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• estazolam

  Monitor Closely (1)brexpiprazole and estazolam both increase sedation. Use Caution/Monitor.

• eszopiclone

  Monitor Closely (1)brexpiprazole and eszopiclone both increase sedation. Use Caution/Monitor.

• ethanol

  Monitor Closely (1)brexpiprazole and ethanol both increase sedation. Use Caution/Monitor.

• ethosuximide

  Monitor Closely (1)brexpiprazole and ethosuximide both increase sedation. Use Caution/Monitor.

• ethotoin

  Monitor Closely (1)brexpiprazole and ethotoin both increase sedation. Use Caution/Monitor.

• etravirine

  Monitor Closely (1)etravirine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• fedratinib

  Monitor Closely (2)fedratinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
  
  fedratinib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• felbamate

  Monitor Closely (1)brexpiprazole and felbamate both increase sedation. Use Caution/Monitor.

• fenfluramine

  Monitor Closely (1)brexpiprazole and fenfluramine both increase sedation. Use Caution/Monitor.

• fentanyl

  Serious - Use Alternative (1)brexpiprazole and fentanyl both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl intranasal

  Serious - Use Alternative (2)brexpiprazole and fentanyl intranasal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl intranasal and brexpiprazole both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl iontophoretic transdermal system

  Serious - Use Alternative (1)brexpiprazole and fentanyl iontophoretic transdermal system both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transdermal

  Serious - Use Alternative (1)brexpiprazole and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transmucosal

  Serious - Use Alternative (1)brexpiprazole and fentanyl transmucosal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of brexpiprazole 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.

• fexofenadine

  Monitor Closely (1)brexpiprazole and fexofenadine both increase sedation. Use Caution/Monitor.

• flibanserin

  Monitor Closely (1)brexpiprazole and flibanserin both increase sedation. Use Caution/Monitor.

• fluconazole

  Monitor Closely (1)fluconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• fluoxetine

  Monitor Closely (1)fluoxetine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• fluphenazine

  Monitor Closely (1)brexpiprazole and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  Monitor Closely (1)brexpiprazole and flurazepam both increase sedation. Use Caution/Monitor.

• fosamprenavir

  Monitor Closely (1)fosamprenavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• fosaprepitant

  Monitor Closely (1)fosaprepitant will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• fosphenytoin

  Monitor Closely (1)fosphenytoin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• gabapentin

  Monitor Closely (2)brexpiprazole and gabapentin both increase sedation. Use Caution/Monitor.
  
  gabapentin, brexpiprazole. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  Monitor Closely (1)gabapentin enacarbil, brexpiprazole. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• ganaxolone

  Monitor Closely (1)brexpiprazole and ganaxolone both increase sedation. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (1)givosiran will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• grapefruit

  Monitor Closely (1)grapefruit will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• guanfacine

  Monitor Closely (1)brexpiprazole and guanfacine both increase sedation. Use Caution/Monitor.

• haloperidol

  Monitor Closely (3)brexpiprazole and haloperidol both increase sedation. Use Caution/Monitor.
  
  haloperidol will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  haloperidol will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• hydrocodone

  Serious - Use Alternative (1)brexpiprazole and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• hydromorphone

  Serious - Use Alternative (1)brexpiprazole and hydromorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• hydroxyzine

  Monitor Closely (1)brexpiprazole and hydroxyzine both increase sedation. Use Caution/Monitor.

• idelalisib

  Monitor Closely (1)idelalisib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• iloperidone

  Monitor Closely (2)iloperidone will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.
  
  brexpiprazole and iloperidone both increase sedation. Use Caution/Monitor.

• imatinib

  Monitor Closely (2)imatinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  imatinib will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• imipramine

  Monitor Closely (2)brexpiprazole and imipramine both increase sedation. Use Caution/Monitor.
  
  imipramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• indinavir

  Monitor Closely (1)indinavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• isoflurane

  Monitor Closely (1)brexpiprazole and isoflurane both increase sedation. Use Caution/Monitor.

• isoniazid

  Monitor Closely (2)isoniazid will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  isoniazid will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of brexpiprazole 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

  Monitor Closely (1)itraconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• ivosidenib

  Serious - Use Alternative (1)ivosidenib will decrease the level or effect of brexpiprazole 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.

• ketamine

  Monitor Closely (1)brexpiprazole and ketamine both increase sedation. Use Caution/Monitor.

• ketoconazole

  Monitor Closely (2)ketoconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  ketoconazole will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• ketotifen, drug-eluting contact lens

  Monitor Closely (1)brexpiprazole and ketotifen, drug-eluting contact lens both increase sedation. Use Caution/Monitor.

• lamotrigine

  Monitor Closely (1)brexpiprazole and lamotrigine both increase sedation. Use Caution/Monitor.

• lapatinib

  Monitor Closely (1)lapatinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• larotrectinib

  Minor (1)larotrectinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lasmiditan

  Monitor Closely (1)lasmiditan, brexpiprazole. 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

  Monitor Closely (1)lemborexant, brexpiprazole. 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

  Monitor Closely (1)lenacapavir will increase the level or effect of brexpiprazole 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.

• levetiracetam

  Monitor Closely (1)brexpiprazole and levetiracetam both increase sedation. Use Caution/Monitor.

• levocetirizine

  Monitor Closely (1)brexpiprazole and levocetirizine both increase sedation. Use Caution/Monitor.

• levoketoconazole

  Monitor Closely (2)levoketoconazole will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  levoketoconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• levorphanol

  Monitor Closely (1)brexpiprazole and levorphanol both increase sedation. Use Caution/Monitor.

• lidocaine

  Monitor Closely (2)lidocaine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  lidocaine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• lonafarnib

  Serious - Use Alternative (1)lonafarnib will increase the level or effect of brexpiprazole 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.

• lopinavir

  Monitor Closely (2)lopinavir will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.
  
  lopinavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• loratadine

  Monitor Closely (1)brexpiprazole and loratadine both increase sedation. Use Caution/Monitor.

• lorazepam

  Monitor Closely (1)brexpiprazole and lorazepam both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (1)lorcaserin will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• lorlatinib

  Monitor Closely (1)lorlatinib will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• loxapine

  Monitor Closely (1)brexpiprazole and loxapine both increase sedation. Use Caution/Monitor.

• lumacaftor/ivacaftor

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• lumateperone

  Monitor Closely (1)brexpiprazole and lumateperone both increase sedation. Use Caution/Monitor.

• lurasidone

  Monitor Closely (1)brexpiprazole and lurasidone both increase sedation. Use Caution/Monitor.

• maprotiline

  Monitor Closely (1)brexpiprazole and maprotiline both increase sedation. Use Caution/Monitor.

• meclizine

  Monitor Closely (1)brexpiprazole and meclizine both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (1)brexpiprazole and meperidine both increase sedation. Use Caution/Monitor.

• meprobamate

  Monitor Closely (1)brexpiprazole and meprobamate both increase sedation. Use Caution/Monitor.

• metaxalone

  Monitor Closely (1)brexpiprazole and metaxalone both increase sedation. Use Caution/Monitor.

• metformin

  Monitor Closely (1)brexpiprazole decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

• methadone

  Monitor Closely (1)methadone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.Serious - Use Alternative (1)brexpiprazole and methadone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methimazole

  Monitor Closely (1)methimazole will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• methocarbamol

  Monitor Closely (1)brexpiprazole and methocarbamol both increase sedation. Use Caution/Monitor.

• methohexital

  Monitor Closely (1)brexpiprazole and methohexital both increase sedation. Use Caution/Monitor.

• methsuximide

  Monitor Closely (1)brexpiprazole and methsuximide both increase sedation. Use Caution/Monitor.

• metoclopramide intranasal

  Serious - Use Alternative (1)brexpiprazole, 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.

• metronidazole

  Monitor Closely (1)metronidazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• midazolam

  Monitor Closely (1)brexpiprazole and midazolam both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (1)midazolam intranasal, brexpiprazole. 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.

• mifepristone

  Monitor Closely (1)mifepristone will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mirtazapine

  Monitor Closely (1)brexpiprazole and mirtazapine both increase sedation. Use Caution/Monitor.

• mitotane

  Monitor Closely (1)mitotane will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• molindone

  Monitor Closely (1)brexpiprazole and molindone both increase sedation. Use Caution/Monitor.

• morphine

  Serious - Use Alternative (1)brexpiprazole and morphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• nafcillin

  Monitor Closely (1)nafcillin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• nalbuphine

  Monitor Closely (1)brexpiprazole and nalbuphine both increase sedation. Use Caution/Monitor.

• nefazodone

  Monitor Closely (2)nefazodone will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  nefazodone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• nelfinavir

  Serious - Use Alternative (1)nelfinavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• netupitant/palonosetron

  Monitor Closely (1)netupitant/palonosetron will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• nevirapine

  Monitor Closely (1)nevirapine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• nicardipine

  Monitor Closely (2)nicardipine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  nicardipine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• nitrous oxide

  Monitor Closely (1)brexpiprazole and nitrous oxide both increase sedation. Use Caution/Monitor.

• nortriptyline

  Monitor Closely (1)brexpiprazole and nortriptyline both increase sedation. Use Caution/Monitor.

• olanzapine

  Monitor Closely (1)brexpiprazole and olanzapine both increase sedation. Use Caution/Monitor.

• oliceridine

  Monitor Closely (1)brexpiprazole and oliceridine both increase sedation. Use Caution/Monitor.

• olopatadine intranasal

  Serious - Use Alternative (1)brexpiprazole 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.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Monitor Closely (2)ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.
  
  ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• opicapone

  Monitor Closely (1)brexpiprazole and opicapone both increase sedation. Use Caution/Monitor.

• opium tincture

  Monitor Closely (1)brexpiprazole and opium tincture both increase sedation. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (1)brexpiprazole and orphenadrine both increase sedation. Use Caution/Monitor.

• oxazepam

  Monitor Closely (1)brexpiprazole and oxazepam both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  Monitor Closely (1)oxcarbazepine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• oxycodone

  Serious - Use Alternative (1)brexpiprazole and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• oxymorphone

  Serious - Use Alternative (1)brexpiprazole and oxymorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• paliperidone

  Monitor Closely (1)brexpiprazole and paliperidone both increase sedation. Use Caution/Monitor.

• panobinostat

  Monitor Closely (1)panobinostat will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• paroxetine

  Monitor Closely (1)paroxetine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

• pentazocine

  Monitor Closely (1)brexpiprazole and pentazocine both increase sedation. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (2)pentobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.
  
  brexpiprazole and pentobarbital both increase sedation. Use Caution/Monitor.

• perampanel

  Monitor Closely (1)brexpiprazole and perampanel both increase sedation. Use Caution/Monitor.

• perphenazine

  Monitor Closely (1)brexpiprazole and perphenazine both increase sedation. Use Caution/Monitor.

• pheniramine

  Monitor Closely (1)brexpiprazole and pheniramine both increase sedation. Use Caution/Monitor.

• phenobarbital

  Monitor Closely (2)brexpiprazole and phenobarbital both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• phenytoin

  Monitor Closely (1)phenytoin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• pimozide

  Monitor Closely (1)brexpiprazole and pimozide both increase sedation. Use Caution/Monitor.

• pomalidomide

  Monitor Closely (1)brexpiprazole and pomalidomide both increase sedation. Use Caution/Monitor.

• posaconazole

  Monitor Closely (1)posaconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• pregabalin

  Monitor Closely (2)pregabalin, brexpiprazole. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
  
  brexpiprazole and pregabalin both increase sedation. Use Caution/Monitor.

• primidone

  Monitor Closely (2)primidone will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.
  
  brexpiprazole and primidone both increase sedation. Use Caution/Monitor.

• prochlorperazine

  Monitor Closely (1)brexpiprazole and prochlorperazine both increase sedation. Use Caution/Monitor.

• promethazine

  Monitor Closely (1)brexpiprazole and promethazine both increase sedation. Use Caution/Monitor.

• propofol

  Monitor Closely (1)brexpiprazole and propofol both increase sedation. Use Caution/Monitor.

• protriptyline

  Monitor Closely (1)brexpiprazole and protriptyline both increase sedation. Use Caution/Monitor.

• pyrilamine

  Monitor Closely (1)brexpiprazole and pyrilamine both increase sedation. Use Caution/Monitor.

• pyrimethamine

  Monitor Closely (1)pyrimethamine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• quazepam

  Monitor Closely (1)brexpiprazole and quazepam both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (1)brexpiprazole and quetiapine both increase sedation. Use Caution/Monitor.

• quinidine

  Monitor Closely (2)quinidine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.
  
  quinidine will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• quinine

  Monitor Closely (1)quinine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• ramelteon

  Monitor Closely (1)brexpiprazole and ramelteon both increase sedation. Use Caution/Monitor.

• ranolazine

  Monitor Closely (1)ranolazine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• remifentanil

  Serious - Use Alternative (1)brexpiprazole and remifentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• remimazolam

  Monitor Closely (1)brexpiprazole and remimazolam both increase sedation. Use Caution/Monitor.

• reserpine

  Monitor Closely (1)brexpiprazole and reserpine both increase sedation. Use Caution/Monitor.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  Monitor Closely (1)rifabutin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• rifapentine

  Monitor Closely (1)rifapentine will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• risperidone

  Monitor Closely (1)brexpiprazole and risperidone both increase sedation. Use Caution/Monitor.

• ritonavir

  Monitor Closely (2)ritonavir will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.
  
  ritonavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• rolapitant

  Monitor Closely (1)rolapitant will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• saquinavir

  Monitor Closely (1)saquinavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• schisandra

  Monitor Closely (1)schisandra will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• scopolamine

  Monitor Closely (1)brexpiprazole and scopolamine both increase sedation. Use Caution/Monitor.

• secobarbital

  Serious - Use Alternative (1)secobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selinexor

  Serious - Use Alternative (1)selinexor, brexpiprazole. 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.

• sertraline

  Monitor Closely (2)sertraline will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  sertraline will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• sevoflurane

  Monitor Closely (1)brexpiprazole and sevoflurane both increase sedation. Use Caution/Monitor.

• sodium oxybate

  Monitor Closely (1)brexpiprazole and sodium oxybate both increase sedation. Use Caution/Monitor.

• St John's Wort

  Monitor Closely (1)St John's Wort will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• stiripentol

  Monitor Closely (1)stiripentol, brexpiprazole. 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.

• sufentanil

  Monitor Closely (1)brexpiprazole and sufentanil both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Monitor Closely (1)brexpiprazole and sufentanil SL both increase sedation. Use Caution/Monitor.

• suvorexant

  Monitor Closely (1)brexpiprazole and suvorexant both increase sedation. Use Caution/Monitor.

• tapentadol

  Monitor Closely (1)brexpiprazole and tapentadol both increase sedation. Use Caution/Monitor.

• tasimelteon

  Monitor Closely (1)brexpiprazole and tasimelteon both increase sedation. Use Caution/Monitor.

• tazemetostat

  Monitor Closely (1)tazemetostat will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• temazepam

  Monitor Closely (1)brexpiprazole and temazepam both increase sedation. Use Caution/Monitor.

• terbinafine

  Monitor Closely (1)terbinafine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• tetrabenazine

  Monitor Closely (1)brexpiprazole and tetrabenazine both increase sedation. Use Caution/Monitor.

• tetracycline

  Monitor Closely (1)tetracycline will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• thalidomide

  Contraindicated (1)brexpiprazole and thalidomide both increase sedation. Contraindicated.

• thioridazine

  Monitor Closely (2)thioridazine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and thioridazine both increase sedation. Use Caution/Monitor.

• thiothixene

  Monitor Closely (1)brexpiprazole and thiothixene both increase sedation. Use Caution/Monitor.

• tiagabine

  Monitor Closely (1)brexpiprazole and tiagabine both increase sedation. Use Caution/Monitor.

• ticagrelor

  Monitor Closely (1)ticagrelor will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• ticlopidine

  Monitor Closely (1)ticlopidine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• tipranavir

  Monitor Closely (1)tipranavir will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• tizanidine

  Monitor Closely (1)brexpiprazole and tizanidine both increase sedation. Use Caution/Monitor.

• tolcapone

  Monitor Closely (1)brexpiprazole and tolcapone both increase sedation. Use Caution/Monitor.

• topiramate

  Monitor Closely (1)brexpiprazole and topiramate both increase sedation. Use Caution/Monitor.

• tramadol

  Monitor Closely (1)brexpiprazole and tramadol both increase sedation. Use Caution/Monitor.

• tranylcypromine

  Monitor Closely (1)tranylcypromine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• trazodone

  Monitor Closely (2)trazodone will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and trazodone both increase sedation. Use Caution/Monitor.

• triazolam

  Monitor Closely (1)brexpiprazole and triazolam both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (1)brexpiprazole and trifluoperazine both increase sedation. Use Caution/Monitor.

• triprolidine

  Monitor Closely (1)brexpiprazole and triprolidine both increase sedation. Use Caution/Monitor.

• tucatinib

  Serious - Use Alternative (1)tucatinib will increase the level or effect of brexpiprazole 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.

• valproic acid

  Monitor Closely (1)brexpiprazole and valproic acid both increase sedation. Use Caution/Monitor.

• verapamil

  Monitor Closely (1)verapamil will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• vigabatrin

  Monitor Closely (1)brexpiprazole and vigabatrin both increase sedation. Use Caution/Monitor.

• voriconazole

  Monitor Closely (1)voriconazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of brexpiprazole 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.

• zaleplon

  Monitor Closely (1)brexpiprazole and zaleplon both increase sedation. Use Caution/Monitor.

• ziconotide

  Monitor Closely (1)brexpiprazole and ziconotide both increase sedation. Use Caution/Monitor.

• zileuton

  Monitor Closely (1)zileuton will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

• ziprasidone

  Monitor Closely (1)brexpiprazole and ziprasidone both increase sedation. Use Caution/Monitor.

• zolpidem

  Monitor Closely (1)brexpiprazole and zolpidem both increase sedation. Use Caution/Monitor.

• zonisamide

  Monitor Closely (1)brexpiprazole and zonisamide both increase sedation. Use Caution/Monitor.