enzyme CYP3A4 metabolism. Use Caution/Monitor.avapritinibMonitor Closely (1)avapritinib and tasimelteon both increase sedation. Use Caution/Monitor.benzhydrocodone/acetaminophenMonitor Closely (1)benzhydrocodone/acetaminophen and tasimelteon both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)benzhydrocodone/acetaminophen, tasimelteon. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.bosentanMonitor Closely (1)bosentan will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducersbrexanoloneMonitor Closely (1)brexanolone, tasimelteon. Either increases toxicity of the other by sedation. Use Caution/Monitor.brexpiprazoleMonitor Closely (1)brexpiprazole and tasimelteon both increase sedation. Use Caution/Monitor.brimonidineMonitor Closely (1)brimonidine and tasimelteon both increase sedation. Use Caution/Monitor.brivaracetamMonitor Closely (1)brivaracetam and tasimelteon both increase sedation. Use Caution/Monitor.buprenorphine subdermal implantMonitor Closely (1)buprenorphine subdermal implant and tasimelteon both increase sedation. Use Caution/Monitor.buprenorphine transdermalMonitor Closely (1)buprenorphine transdermal and tasimelteon both increase sedation. Use Caution/Monitor.buprenorphine, long-acting injectionMonitor Closely (2)tasimelteon 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. buprenorphine, long-acting injection and tasimelteon both increase sedation. Use Caution/Monitor.cannabidiolMonitor Closely (1)cannabidiol, tasimelteon. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.carbamazepineMonitor Closely (1)carbamazepine will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducerscenobamateMonitor Closely (2)cenobamate, tasimelteon. Either increases effects of the other by sedation. Use Caution/Monitor. cenobamate will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.chloramphenicolMonitor Closely (1)chloramphenicol will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cigarette smokingMonitor Closely (1)cigarette smoking will increase the level or effect of tasimelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Tasimelteon exposure in smokers was lower (~40%) than in nonsmokersciprofloxacinMonitor Closely (1)ciprofloxacin will increase the level or effect of tasimelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Avoid coadministration; potentially large increase in tasimelteon exposure and greater risk of adverse reactions with strong CYP1A2 inhibitorsclarithromycinMonitor Closely (1)clarithromycin will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.conivaptanMonitor Closely (1)conivaptan will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cyclophosphamideMinor (1)cyclophosphamide will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.dabrafenibMonitor Closely (1)dabrafenib will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducersdaridorexantMonitor Closely (1)tasimelteon 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. darunavirMonitor Closely (1)darunavir will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.deutetrabenazineMonitor Closely (1)tasimelteon and deutetrabenazine both increase sedation. Use Caution/Monitor.dexamethasoneMonitor Closely (1)dexamethasone will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducersdiazepam intranasalMonitor Closely (1)diazepam intranasal, tasimelteon. 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 tasimelteon both increase sedation. Use Caution/Monitor.efavirenzMonitor Closely (1)efavirenz will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducerselagolixMonitor Closely (1)elagolix decreases levels of tasimelteon 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 DFMonitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.encorafenibMonitor Closely (1)encorafenib, tasimelteon. 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 tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducersepcoritamabMonitor Closely (1)epcoritamab, tasimelteon. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .esketamine intranasalMonitor Closely (1)esketamine intranasal, tasimelteon. 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 tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducersethanolMonitor Closely (1)ethanol and tasimelteon both increase sedation. Use Caution/Monitor.etravirineMonitor Closely (1)etravirine will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducersfedratinibMonitor Closely (1)fedratinib will increase the level or effect of tasimelteon 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, tasimelteon. 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, tasimelteon. 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, tasimelteon. 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, tasimelteon. 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.fexinidazoleMonitor Closely (1)fexinidazole will increase the level or effect of tasimelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)fexinidazole will increase the level or effect of tasimelteon 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)tasimelteon and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.fluvoxamineMonitor Closely (1)fluvoxamine will increase the level or effect of tasimelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. May increase adverse effectsfosamprenavirMonitor Closely (1)fosamprenavir will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fosphenytoinMonitor Closely (1)fosphenytoin will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducersgabapentinMonitor Closely (1)gabapentin, tasimelteon. 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 enacarbilMonitor Closely (1)gabapentin enacarbil, tasimelteon. 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.ganaxoloneMonitor Closely (1)tasimelteon and ganaxolone both increase sedation. Use Caution/Monitor.givosiranSerious - Use Alternative (1)givosiran will increase the level or effect of tasimelteon by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.glofitamabMonitor Closely (1)glofitamab, tasimelteon. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .hydrocodoneSerious - Use Alternative (1)hydrocodone, tasimelteon. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.idelalisibSerious - Use Alternative (1)idelalisib will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substratesimatinibMonitor Closely (1)imatinib will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.indinavirMonitor Closely (1)indinavir will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.isoniazidMonitor Closely (1)isoniazid will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.istradefyllineMonitor Closely (1)istradefylline will increase the level or effect of tasimelteon 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.itraconazoleMonitor Closely (1)itraconazole will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ivosidenibSerious - Use Alternative (1)ivosidenib will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.ketoconazoleMonitor Closely (1)ketoconazole will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.larotrectinibMinor (1)larotrectinib will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lasmiditanMonitor Closely (1)lasmiditan, tasimelteon. 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.lemborexantSerious - Use Alternative (1)lemborexant, tasimelteon. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended.lenacapavirMonitor Closely (1)lenacapavir will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir 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.leniolisibSerious - Use Alternative (1)leniolisib will increase the level or effect of tasimelteon by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid leniolisib with CYP1A2 substrates that have a narrow therapeutic indexlevoketoconazoleMonitor Closely (1)levoketoconazole will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lonafarnibSerious - Use Alternative (1)lonafarnib will increase the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration