affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lurasidoneMonitor Closely (1)lurasidone, ramelteon. Either increases toxicity of the other by sedation. Use Caution/Monitor. Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.maprotilineMonitor Closely (1)maprotiline and ramelteon both increase sedation. Use Caution/Monitor.marijuanaMonitor Closely (1)marijuana and ramelteon both increase sedation. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.melatoninMonitor Closely (1)melatonin and ramelteon both increase sedation. Use Caution/Monitor.meperidineMonitor Closely (1)meperidine and ramelteon both increase sedation. Use Caution/Monitor.meprobamateMonitor Closely (1)meprobamate and ramelteon both increase sedation. Use Caution/Monitor.metaxaloneMonitor Closely (1)metaxalone and ramelteon both increase sedation. Use Caution/Monitor.methadoneMonitor Closely (1)methadone and ramelteon both increase sedation. Use Caution/Monitor.methocarbamolMonitor Closely (1)methocarbamol and ramelteon both increase sedation. Use Caution/Monitor.methylenedioxymethamphetamineMonitor Closely (1)ramelteon increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.metoclopramide intranasalSerious - Use Alternative (1)ramelteon, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.metronidazoleMinor (2)metronidazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. metronidazole will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.mexiletineMonitor Closely (1)mexiletine will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.miconazole vaginalMinor (2)miconazole vaginal will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. miconazole vaginal will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.midazolamMonitor Closely (1)midazolam and ramelteon both increase sedation. Use Caution/Monitor.midazolam intranasalMonitor Closely (1)midazolam intranasal, ramelteon. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.mirtazapineMonitor Closely (1)mirtazapine and ramelteon both increase sedation. Use Caution/Monitor.modafinilMonitor Closely (1)modafinil will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.morphineMonitor Closely (1)morphine and ramelteon both increase sedation. Use Caution/Monitor.motherwortMonitor Closely (1)motherwort and ramelteon both increase sedation. Use Caution/Monitor.moxonidineMonitor Closely (1)moxonidine and ramelteon both increase sedation. Use Caution/Monitor.nabiloneMonitor Closely (1)nabilone and ramelteon both increase sedation. Use Caution/Monitor.nalbuphineMonitor Closely (1)nalbuphine and ramelteon both increase sedation. Use Caution/Monitor.nefazodoneMonitor Closely (1)nefazodone will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.nelfinavirMinor (1)nelfinavir will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nevirapineMinor (1)nevirapine will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nifedipineMinor (1)nifedipine will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nilotinibMinor (1)nilotinib will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nortriptylineMonitor Closely (1)nortriptyline and ramelteon both increase sedation. Use Caution/Monitor.olanzapineMonitor Closely (1)olanzapine and ramelteon both increase sedation. Use Caution/Monitor.oliceridineMonitor Closely (1)oliceridine, ramelteon. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. 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.olopatadine intranasalSerious - Use Alternative (1)ramelteon and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. opium tinctureMonitor Closely (1)opium tincture and ramelteon both increase sedation. Use Caution/Monitor.orphenadrineMonitor Closely (1)orphenadrine and ramelteon both increase sedation. Use Caution/Monitor.oxazepamMonitor Closely (1)oxazepam and ramelteon both increase sedation. Use Caution/Monitor.oxcarbazepineMinor (1)oxcarbazepine will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.oxycodoneMonitor Closely (1)oxycodone and ramelteon both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)ramelteon and oxycodone both increase sedation. Avoid or Use Alternate Drug. Additive CNS depression may lead to hypotension, profound sedation, respiratory depression, or comaoxymorphoneMonitor Closely (1)oxymorphone and ramelteon both increase sedation. Use Caution/Monitor.paliperidoneMonitor Closely (1)paliperidone and ramelteon both increase sedation. Use Caution/Monitor.papaveretumMonitor Closely (1)papaveretum and ramelteon both increase sedation. Use Caution/Monitor.papaverineMonitor Closely (1)papaverine and ramelteon both increase sedation. Use Caution/Monitor.pefloxacinSerious - Use Alternative (1)pefloxacin will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.pentazocineMonitor Closely (1)pentazocine and ramelteon both increase sedation. Use Caution/Monitor.pentobarbitalMonitor Closely (2)pentobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. pentobarbital and ramelteon both increase sedation. Use Caution/Monitor.Minor (2)pentobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. pentobarbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.perphenazineMonitor Closely (1)perphenazine and ramelteon both increase sedation. Use Caution/Monitor.phenobarbitalMonitor Closely (2)phenobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. phenobarbital and ramelteon both increase sedation. Use Caution/Monitor.Minor (2)phenobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. phenobarbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.phenylephrine POMonitor Closely (1)ramelteon increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .phenytoinMinor (1)phenytoin will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.pholcodineMonitor Closely (1)pholcodine and ramelteon both increase sedation. Use Caution/Monitor.pimozideMonitor Closely (1)pimozide and ramelteon both increase sedation. Use Caution/Monitor.pipemidic acidMonitor Closely (1)pipemidic acid will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.posaconazoleMinor (1)posaconazole will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.pregabalinMonitor Closely (1)pregabalin, 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.primidoneMonitor Closely (2)primidone will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. primidone and ramelteon both increase sedation. Use Caution/Monitor.Minor (2)primidone will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. primidone will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.prochlorperazineMonitor Closely (1)prochlorperazine and ramelteon both increase sedation. Use Caution/Monitor.promethazineMonitor Closely (1)promethazine and ramelteon both increase sedation. Use Caution/Monitor.propofolMonitor Closely (1)propofol and ramelteon both increase sedation. Use Caution/Monitor.propylhexedrineMonitor Closely (1)ramelteon increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.protriptylineMonitor Closely (1)protriptyline and ramelteon both increase sedation. Use Caution/Monitor.quazepamMonitor Closely (1)quazepam and ramelteon both increase sedation. Use Caution/Monitor.quetiapineMonitor Closely (1)quetiapine and ramelteon both increase sedation. Use Caution/Monitor.quinupristin/dalfopristinMinor (1)quinupristin/dalfopristin will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.remimazolamMonitor Closely (1)remimazolam, ramelteon. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifabutinMonitor Closely (1)rifabutin will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifampinMonitor Closely (2)rifampin will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. rifampin will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)rifampin will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.rifapentineMinor (2)rifapentine will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. rifapentine will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.risperidoneMonitor Closely (1)risperidone and ramelteon both increase sedation. Use Caution/Monitor.ritlecitinibMonitor Closely (1)ritlecitinib will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Ritlecitinib inhibits CYP1A2 substrates; coadministration increases AUC and peak plasma concentration sensitive substrates, which may increase risk of adverse reactions. Additional monitoring and dosage adjustment may be needed in accordance with product labeling of CYP1A2 substrates. ritonavirMinor (1)ritonavir will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.rufinamideMinor (1)rufinamide will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.sageMinor (1)ramelteon and sage both increase sedation. Minor/Significance Unknown.scullcapMonitor Closely (1)ramelteon and scullcap both increase sedation. Use Caution/Monitor.secobarbitalMonitor Closely (2)secobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. secobarbital and ramelteon both increase sedation. Use Caution/Monitor.Minor (2)secobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. secobarbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.selinexorSerious - Use Alternative (1)selinexor, ramelteon. 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.shepherd's purseMonitor Closely (1)ramelteon and shepherd's purse both increase sedation. Use Caution/Monitor.smokingMonitor Closely (1)smoking will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.sodium oxybateContraindicated (1)ramelteon, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Coadministration with alcohol or sedative hypnotics are contraindicated because of additive CNS depression.somapacitanMonitor Closely (1)somapacitan 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 substratessomatrogonMonitor Closely (1)somatrogon 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 substratessomatropinMonitor Closely (1)somatropin 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 substratesSt John's WortMonitor Closely (1)St John's Wort will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.stiripentolMonitor Closely (1)stiripentol, ramelteon. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.sufentanilMonitor Closely (1)sufentanil and ramelteon both increase sedation. Use Caution/Monitor.sufentanil SLSerious - Use Alternative (1)sufentanil SL, ramelteon. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. 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.sulfamethoxazoleMinor (1)sulfamethoxazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.tapentadolMonitor Closely (1)tapentadol and ramelteon both increase sedation. Use Caution/Monitor.temazepamMonitor Closely (1)temazepam and ramelteon both increase sedation. Use Caution/Monitor.teriflunomideMonitor Closely (1)teriflunomide decreases levels of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.thioridazineMonitor Closely (1)thioridazine and ramelteon both increase sedation. Use Caution/Monitor.thiothixeneMonitor Closely (1)thiothixene and ramelteon both increase sedation. Use Caution/Monitor.tobacco useMonitor Closely (1)tobacco use will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.topiramateMonitor Closely (1)ramelteon and topiramate both increase sedation. Modify Therapy/Monitor Closely.Minor (1)topiramate will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.tramadolMonitor Closely (1)tramadol and ramelteon both increase sedation. Use Caution/Monitor.trazodoneMonitor Closely (1)trazodone and ramelteon both increase sedation. Use Caution/Monitor.triazolamMonitor Closely (1)triazolam and ramelteon both increase sedation. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos and ramelteon both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)trifluoperazine and ramelteon both increase sedation. Use Caution/Monitor.trimipramineMonitor Closely (1)trimipramine and ramelteon both increase sedation. Use Caution/Monitor.triprolidineMonitor Closely (1)triprolidine and ramelteon both increase sedation. Use Caution/Monitor.valerianSerious - Use Alternative (1)valerian and ramelteon both increase sedation. Avoid or Use Alternate Drug.verapamilMinor (1)verapamil will