affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.cimetidineMinor (1)cimetidine will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.ciprofloxacinMonitor Closely (2)ciprofloxacin will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Asenapine has been associated with dose-related prolongation of the QT interval; asenapine should not be used with other agents also known to have this effect. ciprofloxacin and asenapine both increase QTc interval. Use Caution/Monitor. Ciprofloxacin elicits minimal effects on QT interval. Caution if used in combination with other drugs known to affect QT interval or in patients with other risk factors.citalopramMonitor Closely (1)asenapine and citalopram both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.clarithromycinSerious - Use Alternative (1)clarithromycin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.clemastineMonitor Closely (1)asenapine and clemastine both increase sedation. Use Caution/Monitor.clevidipineMonitor Closely (1)asenapine and clevidipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.clobazamMonitor Closely (2)asenapine and clobazam both increase sedation. Use Caution/Monitor. asenapine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).clomipramineMonitor Closely (3)asenapine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. asenapine and clomipramine both increase sedation. Use Caution/Monitor. asenapine and clomipramine both increase QTc interval. Use Caution/Monitor.clonazepamMonitor Closely (1)asenapine and clonazepam both increase sedation. Use Caution/Monitor.clonidineMonitor Closely (1)asenapine and clonidine both increase sedation. Use Caution/Monitor.clorazepateMonitor Closely (1)asenapine and clorazepate both increase sedation. Use Caution/Monitor.clozapineMonitor Closely (1)asenapine and clozapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clozapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.codeineSerious - Use Alternative (1)asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequateMinor (1)asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.crizotinibMonitor Closely (1)crizotinib and asenapine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.cyclobenzaprineMonitor Closely (1)asenapine and cyclobenzaprine both increase sedation. Use Caution/Monitor.cyproheptadineMonitor Closely (1)asenapine and cyproheptadine both increase sedation. Use Caution/Monitor.dantroleneMonitor Closely (1)asenapine and dantrolene both increase sedation. Use Caution/Monitor.daridorexantMonitor Closely (1)asenapine 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. dasatinibSerious - Use Alternative (1)dasatinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.deferasiroxMonitor Closely (1)deferasirox increases levels of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.degarelixSerious - Use Alternative (1)degarelix and asenapine both increase QTc interval. Avoid or Use Alternate Drug.desfluraneMonitor Closely (1)asenapine and desflurane both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)desflurane and asenapine both increase QTc interval. Avoid or Use Alternate Drug.desipramineMonitor Closely (3)asenapine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. asenapine and desipramine both increase sedation. Use Caution/Monitor. asenapine and desipramine both increase QTc interval. Use Caution/Monitor.deutetrabenazineMonitor Closely (3)asenapine and deutetrabenazine both increase sedation. Use Caution/Monitor. asenapine and deutetrabenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation). asenapine and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics.dexbrompheniramineMonitor Closely (1)asenapine and dexbrompheniramine both increase sedation. Use Caution/Monitor.dexchlorpheniramineMonitor Closely (1)asenapine and dexchlorpheniramine both increase sedation. Use Caution/Monitor.dexfenfluramineMinor (1)asenapine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dextroamphetamineMinor (1)asenapine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dextromethorphanMonitor Closely (1)dextromethorphan, 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).Minor (1)asenapine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.diazepamMonitor Closely (1)asenapine and diazepam both increase sedation. Use Caution/Monitor.diclofenacMonitor Closely (1)diclofenac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.difelikefalinMonitor Closely (1)difelikefalin and asenapine both increase sedation. Use Caution/Monitor.difenoxin hclMonitor Closely (1)asenapine and difenoxin hcl both increase sedation. Use Caution/Monitor.diflunisalMonitor Closely (1)diflunisal decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.dihydroergotamineMonitor Closely (1)dihydroergotamine, 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).diltiazemMonitor Closely (1)asenapine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.dimenhydrinateMonitor Closely (1)asenapine and dimenhydrinate both increase sedation. Use Caution/Monitor.diphenhydramineMonitor Closely (1)asenapine and diphenhydramine both increase sedation. Use Caution/Monitor.diphenoxylate hclMonitor Closely (1)asenapine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.disopyramideSerious - Use Alternative (1)asenapine and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.dofetilideSerious - Use Alternative (1)dofetilide increases toxicity of asenapine by QTc interval. Avoid or Use Alternate Drug.dolasetronSerious - Use Alternative (1)dolasetron and asenapine both decrease QTc interval. Avoid or Use Alternate Drug.donepezilSerious - Use Alternative (1)donepezil and asenapine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)asenapine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.doxazosinMonitor Closely (1)asenapine and doxazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.doxepinMonitor Closely (3)asenapine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. doxepin and asenapine both increase QTc interval. Use Caution/Monitor. asenapine and doxepin both increase sedation. Use Caution/Monitor.doxylamineMonitor Closely (1)asenapine and doxylamine both increase sedation. Use Caution/Monitor.dronedaroneContraindicated (1)asenapine and dronedarone both increase QTc interval. Contraindicated.droperidolMonitor Closely (1)asenapine and droperidol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.duloxetineMonitor Closely (1)asenapine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.efavirenzMonitor Closely (1)asenapine and efavirenz both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)efavirenz and asenapine both increase QTc interval. Avoid or Use Alternate Drug.eletriptanMonitor Closely (1)eletriptan, 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).eliglustatSerious - Use Alternative (1)asenapine and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.enalaprilMonitor Closely (1)enalapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.encainideMinor (1)asenapine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.encorafenibSerious - Use Alternative (1)encorafenib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.entacaponeMonitor Closely (1)asenapine and entacapone both increase sedation. Use Caution/Monitor.entrectinibSerious - Use Alternative (1)asenapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.ergoloid mesylatesMonitor Closely (1)ergoloid mesylates, 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).ergotamineMonitor Closely (1)ergotamine, 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).eribulinSerious - Use Alternative (1)eribulin and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Potential for enhanced QTc-prolonging effects; if concurrent use is necessary then ECG monitoring is recommended.erythromycin baseSerious - Use Alternative (1)asenapine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)erythromycin base will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.erythromycin ethylsuccinateSerious - Use Alternative (1)asenapine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)erythromycin ethylsuccinate will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.erythromycin lactobionateSerious - Use Alternative (1)asenapine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)erythromycin lactobionate will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.erythromycin stearateSerious - Use Alternative (1)asenapine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)erythromycin stearate will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.escitalopramSerious - Use Alternative (1)escitalopram increases toxicity of asenapine by QTc interval. Avoid or Use Alternate Drug.esketamine intranasalMonitor Closely (1)esketamine intranasal, asenapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.esmololMonitor Closely (1)asenapine and esmolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.estazolamMonitor Closely (1)asenapine and estazolam both increase sedation. Use Caution/Monitor.eszopicloneMonitor Closely (1)asenapine and eszopiclone both increase sedation. Use Caution/Monitor.ethanolMonitor Closely (1)asenapine and ethanol both increase sedation. Use Caution/Monitor.Minor (1)asenapine, ethanol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension, esp. in Asian pts.ethinylestradiolMinor (1)ethinylestradiol will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.ethosuximideMonitor Closely (1)asenapine and ethosuximide both increase sedation. Use Caution/Monitor.ethotoinMonitor Closely (1)asenapine and ethotoin both increase sedation. Use Caution/Monitor.etodolacMonitor Closely (1)etodolac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.exenatide injectable solutionMonitor Closely (1)asenapine, exenatide injectable solution. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.exenatide injectable suspensionMonitor Closely (1)asenapine, exenatide injectable suspension. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.ezogabineMonitor Closely (1)ezogabine, asenapine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.felbamateMonitor Closely (1)asenapine and felbamate both increase sedation. Use Caution/Monitor.felodipineMonitor Closely (1)asenapine and felodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.fenfluramineMonitor Closely (2)asenapine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately. asenapine and fenfluramine both increase sedation. Use Caution/Monitor.fenoprofenMonitor Closely (1)fenoprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.fentanylMonitor Closely (1)fentanyl, 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).Serious - Use Alternative (1)asenapine and fentanyl both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatefentanyl intranasalSerious - Use Alternative (1)asenapine and fentanyl intranasal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatefentanyl iontophoretic transdermal systemSerious - Use Alternative (1)asenapine and fentanyl iontophoretic transdermal system both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatefentanyl transdermalSerious - Use Alternative (1)asenapine and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatefentanyl transmucosalSerious - Use Alternative (1)asenapine and fentanyl transmucosal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients