by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifabutinMonitor 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.rifampinMonitor 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.rifapentineMonitor 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.risperidoneMonitor Closely (1)brexpiprazole and risperidone both increase sedation. Use Caution/Monitor.ritonavirMonitor 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.rolapitantMonitor 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.rucaparibMonitor 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.saquinavirMonitor 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.schisandraMonitor 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.scopolamineMonitor Closely (1)brexpiprazole and scopolamine both increase sedation. Use Caution/Monitor.secobarbitalSerious - Use Alternative (1)secobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.selinexorSerious - 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.sertralineMonitor 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.sevofluraneMonitor Closely (1)brexpiprazole and sevoflurane both increase sedation. Use Caution/Monitor.sodium oxybateMonitor Closely (1)brexpiprazole and sodium oxybate both increase sedation. Use Caution/Monitor.St John's WortMonitor 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.stiripentolMonitor 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.sufentanilMonitor Closely (1)brexpiprazole and sufentanil both increase sedation. Use Caution/Monitor.sufentanil SLMonitor Closely (1)brexpiprazole and sufentanil SL both increase sedation. Use Caution/Monitor.suvorexantMonitor Closely (1)brexpiprazole and suvorexant both increase sedation. Use Caution/Monitor.tapentadolMonitor Closely (1)brexpiprazole and tapentadol both increase sedation. Use Caution/Monitor.tasimelteonMonitor Closely (1)brexpiprazole and tasimelteon both increase sedation. Use Caution/Monitor.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor 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.temazepamMonitor Closely (1)brexpiprazole and temazepam both increase sedation. Use Caution/Monitor.terbinafineMonitor 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.tetrabenazineMonitor Closely (1)brexpiprazole and tetrabenazine both increase sedation. Use Caution/Monitor.tetracyclineMonitor 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.thalidomideContraindicated (1)brexpiprazole and thalidomide both increase sedation. Contraindicated.thioridazineMonitor 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.thiothixeneMonitor Closely (1)brexpiprazole and thiothixene both increase sedation. Use Caution/Monitor.tiagabineMonitor Closely (1)brexpiprazole and tiagabine both increase sedation. Use Caution/Monitor.ticagrelorMonitor 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.ticlopidineMonitor 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.tipranavirMonitor 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.tizanidineMonitor Closely (1)brexpiprazole and tizanidine both increase sedation. Use Caution/Monitor.tolcaponeMonitor Closely (1)brexpiprazole and tolcapone both increase sedation. Use Caution/Monitor.topiramateMonitor Closely (1)brexpiprazole and topiramate both increase sedation. Use Caution/Monitor.tramadolMonitor Closely (1)brexpiprazole and tramadol both increase sedation. Use Caution/Monitor.tranylcypromineMonitor 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.trazodoneMonitor 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.triazolamMonitor Closely (1)brexpiprazole and triazolam both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)brexpiprazole and trifluoperazine both increase sedation. Use Caution/Monitor.triprolidineMonitor Closely (1)brexpiprazole and triprolidine both increase sedation. Use Caution/Monitor.tucatinibSerious - 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 acidMonitor Closely (1)brexpiprazole and valproic acid both increase sedation. Use Caution/Monitor.verapamilMonitor 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.vigabatrinMonitor Closely (1)brexpiprazole and vigabatrin both increase sedation. Use Caution/Monitor.voriconazoleMonitor 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.voxelotorSerious - 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.zaleplonMonitor Closely (1)brexpiprazole and zaleplon both increase sedation. Use Caution/Monitor.ziconotideMonitor Closely (1)brexpiprazole and ziconotide both increase sedation. Use Caution/Monitor.zileutonMonitor 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.ziprasidoneMonitor Closely (1)brexpiprazole and ziprasidone both increase sedation. Use Caution/Monitor.zolpidemMonitor Closely (1)brexpiprazole and zolpidem both increase sedation. Use Caution/Monitor.zonisamideMonitor Closely (1)brexpiprazole and zonisamide both increase sedation. Use Caution/Monitor. >10% MDD Akathisia (4-14%) 1-10% MDD Headache (4-9%) Increased weight (6-8%) Nasopharyngitis (3-7%) Somnolence (4-6%) Fatigue (3-5%) Tremor (2-5%) Dizziness (1-5%) Blood cortisol decreased (3-4%) Anxiety (2-4%) Restlessness (2-4%) Increased appetite (2-3%) Constipation (1-3%) Schizophrenia (adults) Akathisia (4-7%) Dyspepsia (2-6%) Increased weight (3-4%) Blood creatinine phosphokinase increased (3-4%) Tremor (2-3%) Sedation (2-3%) Diarrhea (1-3%) Agitation associated with Alzheimer dementia Headache (7-9%) Insomnia (2-5%) Dizziness (1-5%) Nasopharyngitis (2-4%) Somnolence (2-4%) EPS-related adverse reactions (3%) Urinary tract infection (2-3%) Akathisia (1%) Frequency Not Defined Eye disorders: Blurred vision Gastrointestinal disorders: Nausea, dry mouth, salivary hypersecretion, abdominal pain, flatulence Infections and infestations: Urinary tract infection Investigations: Blood prolactin increased Musculoskeletal and connective tissue disorders: Myalgia Psychiatric disorders: Abnormal dreams, insomnia Skin and SC tissue disorders: Hyperhidrosis Postmarketing Reports Neuroleptic malignant syndrome Black Box Warnings Increased mortality in elderly patients with dementia-related psychosis Elderly patients with dementia-related psychosis when treated with antipsychotic drugs are at an increased risk of death Not approved for treatment of patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer disease Suicidal thoughts and behaviors Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged ≤24 years Closely monitor for clinical worsening, and for emergence of suicidal thoughts and behaviors Safety and effectiveness not established in pediatric patients with MDD Contraindications Hypersensitivity to brexpiprazole or any of its components; reactions have included rash, facial swelling, urticaria, and angioedema Cautions Increased mortality in elderly patients with dementia-related psychosis; in placebo-controlled trials, majority of patients treated with atypical antipsychotic drugs had a 1.6-1.7x higher risk of death than placebo Increased mortality in elderly patients with dementia-related psychosis; in placebo-controlled trials; most of reported deaths were either cardiovascular or infectious in nature Higher incidence of stroke and transient ischemic attack, including fatal stroke reported; not approved for treatment of patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer’s disease Suicidal thoughts and behaviors reported in patients ≤24 years who are taking antidepressant drugs; unknown whether risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use (ie, >4 months) May cause leukopenia, neutropenia, and agranulocytosis; monitor and discontinue if severe neutropenia (ANC <1000/mm3); in patients with a pre-existing low WBC or ANC or a history of drug-induced leukopenia or neutropenia, perform a complete blood cell count (CBC) frequently during the first few months of therapy Orthostatic hypotension or syncope may occur; the risk is greatest during initial dose titration and when increasing the dose; monitor orthostatic vital signs in patients who are vulnerable to hypotension, (eg, elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medication, patients with known cardiovascular disease, patients with cerebrovascular disease) May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy Caution with a history of seizures or with conditions/drugs that potentially lower the seizure threshold May disrupt the body’s ability to reduce core body temperature; use with caution in patients who experience these conditions Esophageal dysmotility and aspiration pneumonia reported; use cautiously in patients at risk for aspiration Sedation and hypersomnia reported that may cause impaired judgement, thinking, or motor skills; exercise caution if operating hazardous machinery, including motor vehicles, until certain therapy does not adversely affect them Postmarketing case reports suggest that patients can experience intense urges, particularly for gambling, and inability to control urges; consider dose reduction or stopping medication if a patient develops such urges Neuroleptic malignant syndrome (NMS) Potentially fatal NMS has been associated with antipsychotic drugs administration Clinical manifestations are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and