promethazine both increase sedation. Use Caution/Monitor.propafenoneasenapine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.propofolasenapine and propofol both increase sedation. Use Caution/Monitor.propranololasenapine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.asenapine and propranolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.protriptylineasenapine and protriptyline both increase QTc interval. Use Caution/Monitor.asenapine and protriptyline both increase sedation. Use Caution/Monitor.pyrilamineasenapine and pyrilamine both increase sedation. Use Caution/Monitor.quazepamasenapine and quazepam both increase sedation. Use Caution/Monitor.quetiapinequetiapine, asenapine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.asenapine and quetiapine both increase sedation. Use Caution/Monitor.quinaprilquinapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.quinineasenapine and quinine both increase QTc interval. Use Caution/Monitor.ramelteonasenapine and ramelteon both increase sedation. Use Caution/Monitor.ramiprilramipril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.remimazolamremimazolam, asenapine. 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.repaglinideasenapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.reserpineasenapine and reserpine both increase sedation. Use Caution/Monitor.rifampinrifampin will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.rilpivirinerilpivirine increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.risperidoneasenapine and risperidone both increase sedation. Use Caution/Monitor.rosiglitazoneasenapine, rosiglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.salicylates (non-asa)salicylates (non-asa) decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.salsalatesalsalate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.saxagliptinasenapine, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.scopolamineasenapine and scopolamine both increase sedation. Use Caution/Monitor.selegilineselegiline, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).selpercatinibselpercatinib increases toxicity of asenapine by QTc interval. Use Caution/Monitor.sevofluraneasenapine and sevoflurane both increase sedation. Use Caution/Monitor.silodosinasenapine and silodosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.sitagliptinasenapine, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.sodium oxybateasenapine and sodium oxybate both increase sedation. Use Caution/Monitor.sodium sulfate/?magnesium sulfate/potassium chloridesodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.sodium sulfate/?magnesium sulfate/potassium chloride increases effects of asenapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.sodium sulfate/potassium sulfate/magnesium sulfatesodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.sodium sulfate/potassium sulfate/magnesium sulfate increases effects of asenapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.sorafenibsorafenib and asenapine both increase QTc interval. Use Caution/Monitor.sotalolasenapine and sotalol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.stiripentolstiripentol, asenapine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.sufentanilasenapine and sufentanil both increase sedation. Use Caution/Monitor.sufentanil SLasenapine and sufentanil SL both increase sedation. Use Caution/Monitor.sulfasalazinesulfasalazine decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.sulindacsulindac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.sumatriptansumatriptan, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).sumatriptan intranasalsumatriptan intranasal, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).suvorexantasenapine and suvorexant both increase sedation. Use Caution/Monitor.tadalafiltadalafil increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.tapentadolasenapine and tapentadol both increase sedation. Use Caution/Monitor.tasimelteonasenapine and tasimelteon both increase sedation. Use Caution/Monitor.temazepamasenapine and temazepam both increase sedation. Use Caution/Monitor.terazosinasenapine and terazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.tetrabenazineasenapine and tetrabenazine both increase sedation. Use Caution/Monitor.thioridazineasenapine and thioridazine both increase sedation. Use Caution/Monitor.thiothixeneasenapine and thiothixene both increase sedation. Use Caution/Monitor.tiagabineasenapine and tiagabine both increase sedation. Use Caution/Monitor.timololasenapine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.asenapine and timolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.tizanidineasenapine and tizanidine both increase sedation. Use Caution/Monitor.tolazamideasenapine, tolazamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.tolbutamideasenapine, tolbutamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.tolcaponeasenapine and tolcapone both increase sedation. Use Caution/Monitor.tolfenamic acidtolfenamic acid decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.tolmetintolmetin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.topiramateasenapine and topiramate both increase sedation. Use Caution/Monitor.tramadolasenapine and tramadol both increase sedation. Use Caution/Monitor.trandolapriltrandolapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.tranylcyprominetranylcypromine, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).trazodoneasenapine and trazodone both increase sedation. Use Caution/Monitor.triazolamasenapine and triazolam both increase sedation. Use Caution/Monitor.triclabendazoletriclabendazole and asenapine both increase QTc interval. Use Caution/Monitor.trifluoperazineasenapine and trifluoperazine both increase sedation. Use Caution/Monitor.trimipramineasenapine and trimipramine both increase QTc interval. Use Caution/Monitor.triprolidineasenapine and triprolidine both increase sedation. Use Caution/Monitor.valbenazinevalbenazine and asenapine both increase QTc interval. Use Caution/Monitor.valproic acidasenapine and valproic acid both increase sedation. Use Caution/Monitor.vardenafilvardenafil increases effects of asenapine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypotension.venlafaxinevenlafaxine, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).verapamilasenapine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.vigabatrinasenapine and vigabatrin both increase sedation. Use Caution/Monitor.vilazodonevilazodone, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).voclosporinvoclosporin, asenapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.zaleplonasenapine and zaleplon both increase sedation. Use Caution/Monitor.ziconotideasenapine and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneasenapine and ziprasidone both increase sedation. Use Caution/Monitor.zolmitriptanzolmitriptan, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).zolpidemasenapine and zolpidem both increase sedation. Use Caution/Monitor.zonisamideasenapine and zonisamide both increase sedation. Use Caution/Monitor.zotepineasenapine and zotepine both increase anti-hypertensive channel blocking. Use Caution/Monitor.Minor (54)amobarbitalamobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.aripiprazoleasenapine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.armodafinilarmodafinil will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.brimonidinebrimonidine increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown.butabarbitalbutabarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.butalbitalbutalbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.butcher's broomasenapine, butcher's broom. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.carbamazepinecarbamazepine will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.chlorpromazineasenapine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.cigarette smokingcigarette smoking will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.cimetidinecimetidine will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.codeineasenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dexfenfluramineasenapine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dextroamphetamineasenapine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dextromethorphanasenapine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.donepezilasenapine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.encainideasenapine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.erythromycin baseerythromycin base will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.erythromycin ethylsuccinateerythromycin ethylsuccinate will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.erythromycin lactobionateerythromycin lactobionate will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.erythromycin stearateerythromycin stearate will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.ethanolasenapine, ethanol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension, esp. in Asian pts.ethinylestradiolethinylestradiol will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.fesoterodineasenapine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.fluphenazineasenapine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.galantamineasenapine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.isoniazidisoniazid will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.loratadineasenapine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.mexiletinemexiletine will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.modafinilmodafinil will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.peginterferon alfa 2apeginterferon alfa 2a will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.pentobarbitalpentobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.perhexilineasenapine will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.perphenazineasenapine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.phenobarbitalphenobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.phenylephrineasenapine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.phenylephrine POasenapine, phenylephrine PO. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.pipemidic acidpipemidic acid will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.primidoneprimidone will