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 ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.darunavirMinor (1)darunavir will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.dasatinibMinor (1)dasatinib will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.deferasiroxMonitor Closely (1)deferasirox increases levels of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.desipramineMonitor Closely (1)desipramine and ramelteon both increase sedation. Use Caution/Monitor.deutetrabenazineMonitor Closely (1)ramelteon and deutetrabenazine both increase sedation. Use Caution/Monitor.dexamethasoneMinor (1)dexamethasone will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.dexchlorpheniramineMonitor Closely (1)dexchlorpheniramine and ramelteon both increase sedation. Use Caution/Monitor.dexfenfluramineMonitor Closely (1)ramelteon increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.dexmedetomidineMonitor Closely (1)dexmedetomidine and ramelteon both increase sedation. Use Caution/Monitor.dextromoramideMonitor Closely (1)dextromoramide and ramelteon both increase sedation. Use Caution/Monitor.DHEA, herbalMinor (1)DHEA, herbal will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.diamorphineMonitor Closely (1)diamorphine and ramelteon both increase sedation. Use Caution/Monitor.diazepamMonitor Closely (1)diazepam and ramelteon both increase sedation. Use Caution/Monitor.diazepam intranasalMonitor Closely (1)diazepam intranasal, ramelteon. 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 ramelteon both increase sedation. Use Caution/Monitor.difenoxin hclMonitor Closely (1)difenoxin hcl and ramelteon both increase sedation. Use Caution/Monitor.dimenhydrinateMonitor Closely (1)dimenhydrinate and ramelteon both increase sedation. Use Caution/Monitor.diphenhydramineMonitor Closely (1)diphenhydramine and ramelteon both increase sedation. Use Caution/Monitor.diphenoxylate hclMonitor Closely (1)diphenoxylate hcl and ramelteon both increase sedation. Use Caution/Monitor.dipipanoneMonitor Closely (1)dipipanone and ramelteon both increase sedation. Use Caution/Monitor.disulfiramMinor (1)disulfiram will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.donepezilMonitor Closely (1)donepezil will increase the level or effect of ramelteon by unspecified interaction mechanism. Use Caution/Monitor. AUC and Cmax increased by 100% and 87% respectively.dopexamineMonitor Closely (1)ramelteon increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.doxepinMonitor Closely (2)doxepin and ramelteon both increase sedation. Use Caution/Monitor. doxepin will increase the level or effect of ramelteon by unspecified interaction mechanism. Use Caution/Monitor. AUC and Cmax increased by 66% and 69% respectively.doxylamineMonitor Closely (1)doxylamine and ramelteon both increase sedation. Use Caution/Monitor.dronedaroneMinor (1)dronedarone will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.droperidolMonitor Closely (1)droperidol and ramelteon both increase sedation. Use Caution/Monitor.efavirenzMonitor Closely (1)efavirenz will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)efavirenz will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.epcoritamabMonitor Closely (1)epcoritamab, ramelteon. 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. .erythromycin baseMonitor Closely (2)erythromycin base will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. erythromycin base will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.erythromycin ethylsuccinateMonitor Closely (2)erythromycin ethylsuccinate will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. erythromycin ethylsuccinate will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.erythromycin lactobionateMonitor Closely (2)erythromycin lactobionate will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. erythromycin lactobionate will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.erythromycin stearateMonitor Closely (2)erythromycin stearate will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. erythromycin stearate will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.esketamine intranasalMonitor Closely (1)esketamine intranasal, ramelteon. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.eslicarbazepine acetateMinor (1)eslicarbazepine acetate will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.estazolamMonitor Closely (1)estazolam and ramelteon both increase sedation. Use Caution/Monitor.ethanolMonitor Closely (1)ethanol and ramelteon both increase sedation. Use Caution/Monitor.ethinylestradiolMonitor Closely (1)ethinylestradiol will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Minor (1)ethinylestradiol will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.etomidateMonitor Closely (1)etomidate and ramelteon both increase sedation. Use Caution/Monitor.etravirineMinor (2)etravirine will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. etravirine will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.eucalyptusMinor (1)eucalyptus and ramelteon both increase sedation. Minor/Significance Unknown.fenfluramineMonitor Closely (1)ramelteon increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.fentanylSerious - Use Alternative (1)fentanyl, ramelteon. 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, ramelteon. 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, ramelteon. 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, ramelteon. 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 ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.flibanserinMonitor Closely (1)ramelteon and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.fluconazoleMinor (2)fluconazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. fluconazole will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fluoxetineMonitor Closely (1)fluoxetine will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.fluphenazineMonitor Closely (1)fluphenazine and ramelteon both increase sedation. Use Caution/Monitor.flurazepamMonitor Closely (1)flurazepam and ramelteon both increase sedation. Use Caution/Monitor.fluvoxamineContraindicated (1)fluvoxamine will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated.Monitor Closely (1)fluvoxamine will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.fosamprenavirMinor (1)fosamprenavir will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fosaprepitantMinor (1)fosaprepitant will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fosphenytoinMinor (1)fosphenytoin will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.gabapentinMonitor Closely (1)gabapentin, ramelteon. 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, ramelteon. 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)ramelteon and ganaxolone both increase sedation. Use Caution/Monitor.givosiranSerious - Use Alternative (1)givosiran will increase the level or effect of ramelteon 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, ramelteon. 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. .grapefruitMinor (1)grapefruit will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.griseofulvinMinor (1)griseofulvin will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.haloperidolMonitor Closely (1)haloperidol and ramelteon both increase sedation. Use Caution/Monitor.hydrocodoneSerious - Use Alternative (1)hydrocodone, ramelteon. 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 ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.hydromorphoneMonitor Closely (1)hydromorphone and ramelteon both increase sedation. Use Caution/Monitor.hydroxyzineMonitor Closely (1)hydroxyzine and ramelteon both increase sedation. Use Caution/Monitor.iloperidoneMonitor Closely (1)iloperidone and ramelteon both increase sedation. Use Caution/Monitor.imatinibMonitor Closely (1)imatinib will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.imipramineMonitor Closely (1)imipramine and ramelteon both increase sedation. Use Caution/Monitor.indinavirMinor (1)indinavir will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.isoniazidMonitor Closely (1)isoniazid will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Minor (1)isoniazid will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.itraconazoleMonitor Closely (1)itraconazole will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ketamineMonitor Closely (1)ketamine and ramelteon both increase sedation. Use Caution/Monitor.ketoconazoleMonitor Closely (1)ketoconazole will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ketoconazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.ketotifen, ophthalmicMonitor Closely (1)ketotifen, ophthalmic and ramelteon both increase sedation. Use Caution/Monitor.lapatinibMinor (1)lapatinib will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lasmiditanMonitor Closely (1)lasmiditan, ramelteon. 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.leflunomideMinor (1)leflunomide will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.lemborexantSerious - Use Alternative (1)lemborexant, ramelteon. 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.leniolisibSerious - Use Alternative (1)leniolisib will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid leniolisib with CYP1A2 substrates that have a narrow therapeutic indexletermovirMonitor Closely (1)letermovir increases levels of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levoketoconazoleMonitor Closely (1)levoketoconazole will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)levoketoconazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.levorphanolMonitor Closely (1)levorphanol and ramelteon both increase sedation. Use Caution/Monitor.lofepramineMonitor Closely (1)lofepramine and ramelteon both increase sedation. Use Caution/Monitor.lofexidineMonitor Closely (1)lofexidine and ramelteon both increase sedation. Use Caution/Monitor.lonapegsomatropinMonitor Closely (1)lonapegsomatropin will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratesloprazolamMonitor Closely (1)loprazolam and ramelteon both increase sedation. Use Caution/Monitor.lorazepamMonitor Closely (1)lorazepam and ramelteon both increase sedation. Use Caution/Monitor.lormetazepamMonitor Closely (1)lormetazepam and ramelteon both increase sedation. Use Caution/Monitor.loxapineMonitor Closely (1)loxapine and ramelteon both increase sedation. Use Caution/Monitor.loxapine inhaledMonitor Closely (1)loxapine inhaled and ramelteon both increase sedation. Use Caution/Monitor.lumefantrineMinor (1)lumefantrine will decrease the level or effect of ramelteon by