Therapy/Monitor Closely. Dosage adjustments of suvorexant may be necessarybuprenorphine transdermalMonitor Closely (1)suvorexant and buprenorphine transdermal both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarybuprenorphine, long-acting injectionMonitor Closely (2)buprenorphine, long-acting injection and suvorexant both increase sedation. Use Caution/Monitor. suvorexant increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.butorphanolMonitor Closely (1)suvorexant and butorphanol both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarycarbamazepineMonitor Closely (1)carbamazepine will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/daycenobamateMonitor Closely (2)cenobamate, suvorexant. Either increases effects of the other by sedation. Use Caution/Monitor. cenobamate will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.ceritinibSerious - Use Alternative (1)ceritinib will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorschloramphenicolSerious - Use Alternative (1)chloramphenicol will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.chlordiazepoxideMonitor Closely (1)suvorexant and chlordiazepoxide both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarycimetidineMonitor Closely (1)cimetidine will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsclarithromycinSerious - Use Alternative (1)clarithromycin increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.clomipramineMonitor Closely (1)suvorexant and clomipramine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessaryclonazepamMonitor Closely (1)suvorexant and clonazepam both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessaryclorazepateMonitor Closely (1)suvorexant and clorazepate both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessaryclozapineMonitor Closely (1)clozapine will increase the level or effect of suvorexant by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorscobicistatSerious - Use Alternative (1)cobicistat will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.codeineMonitor Closely (1)suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessaryconivaptanSerious - Use Alternative (1)conivaptan increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.crizotinibMonitor Closely (1)crizotinib will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorscyclophosphamideMinor (1)cyclophosphamide will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cyclosporineMonitor Closely (1)cyclosporine will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsdabigatranMonitor Closely (1)suvorexant will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/mindabrafenibMonitor Closely (1)dabrafenib will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/daydaridorexantMonitor Closely (1)suvorexant 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. darunavirSerious - Use Alternative (1)darunavir increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.desipramineMonitor Closely (1)suvorexant and desipramine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarydeutetrabenazineMonitor Closely (1)suvorexant and deutetrabenazine both increase sedation. Use Caution/Monitor.dexamethasoneMonitor Closely (1)dexamethasone will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/daydiazepamMonitor Closely (1)suvorexant and diazepam both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarydiazepam intranasalMonitor Closely (1)diazepam intranasal, suvorexant. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.difelikefalinMonitor Closely (1)difelikefalin and suvorexant both increase sedation. Use Caution/Monitor.digoxinMonitor Closely (1)suvorexant will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Suvorexant may cause a slight increase in digoxin levelsdiltiazemMonitor Closely (1)diltiazem will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsdoxepinMonitor Closely (1)suvorexant and doxepin both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarydoxycyclineMonitor Closely (1)doxycycline will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsdronedaroneMonitor Closely (1)dronedarone will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsduvelisibMonitor Closely (1)duvelisib will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.edoxabanSerious - Use Alternative (1)suvorexant will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommendedefavirenzSerious - Use Alternative (1)efavirenz will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/dayelagolixMonitor Closely (1)elagolix decreases levels of suvorexant 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.elvitegravir/cobicistat/emtricitabine/tenofovir DFSerious - Use Alternative (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.encorafenibMonitor Closely (1)encorafenib, suvorexant. 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.enzalutamideMonitor Closely (1)enzalutamide will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/dayerythromycin baseMonitor Closely (1)erythromycin base will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorserythromycin ethylsuccinateMonitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorserythromycin lactobionateMonitor Closely (1)erythromycin lactobionate will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorserythromycin stearateMonitor Closely (1)erythromycin stearate will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsesketamine intranasalMonitor Closely (1)esketamine intranasal, suvorexant. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.eslicarbazepine acetateMonitor Closely (1)eslicarbazepine acetate will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/dayethanolMonitor Closely (1)suvorexant and ethanol both increase sedation. Modify Therapy/Monitor Closely. Advise patient not to consume alcohol because of additive CNS depressant effectsetravirineMonitor Closely (1)etravirine will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/dayfedratinibMonitor Closely (1)fedratinib will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.fentanylSerious - Use Alternative (1)fentanyl, suvorexant. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.fentanyl intranasalSerious - Use Alternative (1)fentanyl intranasal, suvorexant. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.fentanyl transdermalSerious - Use Alternative (1)fentanyl transdermal, suvorexant. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.fentanyl transmucosalSerious - Use Alternative (1)fentanyl transmucosal, suvorexant. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.fexinidazoleSerious - Use Alternative (1)fexinidazole will increase the level or effect of suvorexant 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.flibanserinMonitor Closely (1)suvorexant and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.fluconazoleMonitor Closely (1)fluconazole will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsfosamprenavirSerious - Use Alternative (1)fosamprenavir increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.fosaprepitantMonitor Closely (1)fosaprepitant will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsfosphenytoinMonitor Closely (1)fosphenytoin will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/daygabapentinMonitor Closely (1)gabapentin, suvorexant. 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