by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fosphenytoinfosphenytoin will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.grapefruitgrapefruit will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.griseofulvingriseofulvin will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.hydrocortisonehydrocortisone will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.indinavirindinavir will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.isoniazidisoniazid will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lapatiniblapatinib will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lumefantrinelumefantrine will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.marijuanamarijuana will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.metronidazolemetronidazole will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.miconazole vaginalmiconazole vaginal will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nelfinavirnelfinavir will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nevirapinenevirapine will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nifedipinenifedipine will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nilotinibnilotinib will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.oxcarbazepineoxcarbazepine will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.pentobarbitalpentobarbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.phenobarbitalphenobarbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.phenytoinphenytoin will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.posaconazoleposaconazole will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.primidoneprimidone will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.quinupristin/dalfopristinquinupristin/dalfopristin will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.rifapentinerifapentine will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ritonavirritonavir will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.rufinamiderufinamide will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.secobarbitalsecobarbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.topiramatetopiramate will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.verapamilverapamil will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.voriconazolevoriconazole will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.acrivastineMonitor Closely (1)acrivastine and zaleplon both increase sedation. Use Caution/Monitor.amisulprideMonitor Closely (1)amisulpride and zaleplon both increase sedation. Use Caution/Monitor.amobarbitalMinor (1)amobarbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.aprepitantMinor (1)aprepitant will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.armodafinilMinor (1)armodafinil will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.artemether/lumefantrineMinor (1)artemether/lumefantrine will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.asenapineMonitor Closely (1)asenapine and zaleplon both increase sedation. Use Caution/Monitor.asenapine transdermalMonitor Closely (1)asenapine transdermal and zaleplon both increase sedation. Use Caution/Monitor.atazanavirMinor (1)atazanavir will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.avapritinibMonitor Closely (1)avapritinib and zaleplon both increase sedation. Use Caution/Monitor.benzhydrocodone/acetaminophenMonitor Closely (1)benzhydrocodone/acetaminophen and zaleplon both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)benzhydrocodone/acetaminophen, zaleplon. 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.bosentanMinor (1)bosentan will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.brexanoloneMonitor Closely (1)brexanolone, zaleplon. Either increases toxicity of the other by sedation. Use Caution/Monitor.brexpiprazoleMonitor Closely (1)brexpiprazole and zaleplon both increase sedation. Use Caution/Monitor.brimonidineMonitor Closely (1)brimonidine and zaleplon both increase sedation. Use Caution/Monitor.brivaracetamMonitor Closely (1)brivaracetam and zaleplon both increase sedation. Use Caution/Monitor.buprenorphine subdermal implantMonitor Closely (1)buprenorphine subdermal implant and zaleplon both increase sedation. Use Caution/Monitor.buprenorphine transdermalMonitor Closely (1)buprenorphine transdermal and zaleplon both increase sedation. Use Caution/Monitor.buprenorphine, long-acting injectionMonitor Closely (2)buprenorphine, long-acting injection and zaleplon both increase sedation. Use Caution/Monitor. zaleplon 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.butabarbitalMinor (1)butabarbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.butalbitalMinor (1)butalbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.calcium/magnesium/potassium/sodium oxybatesContraindicated (1)zaleplon, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Coadministration with alcohol or sedative hypnotics are contraindicated because of additive CNS depression.carbamazepineMonitor Closely (1)carbamazepine will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cenobamateMonitor Closely (1)cenobamate, zaleplon. Either increases effects of the other by sedation. Use Caution/Monitor.cimetidineMonitor Closely (1)cimetidine will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.clarithromycinMinor (1)clarithromycin will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.clobazamMonitor Closely (1)zaleplon, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).conivaptanMinor (1)conivaptan will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cyclosporineMinor (1)cyclosporine will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.daridorexantMonitor Closely (1)zaleplon 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. darifenacinMinor (1)darifenacin will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.darunavirMinor (1)darunavir will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.dasatinibMinor (1)dasatinib will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.deutetrabenazineMonitor Closely (1)zaleplon and deutetrabenazine both increase sedation. Use Caution/Monitor.dexamethasoneMinor (1)dexamethasone will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.DHEA, herbalMinor (1)DHEA, herbal will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.diazepam intranasalMonitor Closely (1)diazepam intranasal, zaleplon. 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 zaleplon both increase sedation. Use Caution/Monitor.dronedaroneMinor (1)dronedarone will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.efavirenzMinor (1)efavirenz will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.erythromycin baseMonitor Closely (1)erythromycin base will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.erythromycin ethylsuccinateMonitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.erythromycin lactobionateMonitor Closely (1)erythromycin lactobionate will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.erythromycin stearateMonitor Closely (1)erythromycin stearate will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.esketamine intranasalMonitor Closely (1)esketamine intranasal, zaleplon. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.eslicarbazepine acetateMinor (1)eslicarbazepine acetate will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.etravirineMinor (1)etravirine will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fentanylSerious - Use Alternative (1)fentanyl, zaleplon. 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, zaleplon. 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, zaleplon. 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, zaleplon. 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.flibanserinMonitor Closely (1)zaleplon and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.fluconazoleMinor (1)fluconazole will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fluvoxamineMonitor Closely (1)fluvoxamine will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.fosamprenavirMinor (1)fosamprenavir will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fosaprepitantMinor (1)fosaprepitant will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fosphenytoinMinor (1)fosphenytoin will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.gabapentinMonitor Closely (1)gabapentin, zaleplon. 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, zaleplon. 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)zaleplon and ganaxolone both increase sedation. Use Caution/Monitor.grapefruitMinor (1)grapefruit will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.griseofulvinMinor (1)griseofulvin will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.hydrocodoneSerious - Use Alternative (1)hydrocodone, zaleplon. 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.hydrocortisoneMinor (1)hydrocortisone will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.indinavirMinor (1)indinavir will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.isoniazidMinor (1)isoniazid will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.itraconazoleMonitor Closely (1)itraconazole will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ketoconazoleMonitor Closely (1)ketoconazole will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lapatinibMinor (1)lapatinib will increase the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lasmiditanMonitor Closely (1)lasmiditan, zaleplon. 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