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)lithium and asenapine both increase QTc interval. Avoid or Use Alternate Drug.lofepramineMonitor Closely (1)asenapine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.lofexidineMonitor Closely (1)asenapine and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.loperamideSerious - Use Alternative (1)asenapine and loperamide both increase QTc interval. Avoid or Use Alternate Drug.lopinavirSerious - Use Alternative (1)asenapine and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.loratadineMonitor Closely (1)asenapine and loratadine both increase sedation. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.lorazepamMonitor Closely (1)asenapine and lorazepam both increase sedation. Use Caution/Monitor.lorcaserinMonitor Closely (1)lorcaserin, 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).lornoxicamMonitor Closely (1)lornoxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.loxapineMonitor Closely (1)asenapine and loxapine both increase sedation. Use Caution/Monitor.lumateperoneMonitor Closely (1)asenapine and lumateperone both increase sedation. Use Caution/Monitor.lurasidoneMonitor Closely (1)asenapine and lurasidone both increase sedation. Use Caution/Monitor.macimorelinSerious - Use Alternative (1)macimorelin and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.maprotilineMonitor Closely (1)asenapine and maprotiline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.maravirocMonitor Closely (1)maraviroc, asenapine. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration may increase risk of orthostatic hypotension.meclizineMonitor Closely (1)asenapine and meclizine both increase sedation. Use Caution/Monitor.meclofenamateMonitor Closely (1)meclofenamate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.mefenamic acidMonitor Closely (1)mefenamic acid decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.mefloquineSerious - Use Alternative (1)mefloquine increases toxicity of asenapine by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.meloxicamMonitor Closely (1)meloxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.meperidineMonitor Closely (2)meperidine, 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). asenapine and meperidine both increase sedation. Use Caution/Monitor.meprobamateMonitor Closely (1)asenapine and meprobamate both increase sedation. Use Caution/Monitor.metaxaloneMonitor Closely (1)asenapine and metaxalone both increase sedation. Use Caution/Monitor.metforminMonitor Closely (1)asenapine, metformin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.methadoneMonitor Closely (1)methadone, 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 (2)asenapine and methadone both increase QTc interval. Avoid or Use Alternate Drug. asenapine and methadone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatemethamphetamineMonitor Closely (1)asenapine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.methocarbamolMonitor Closely (1)asenapine and methocarbamol both increase sedation. Use Caution/Monitor.methohexitalMonitor Closely (1)asenapine and methohexital both increase sedation. Use Caution/Monitor.methsuximideMonitor Closely (1)asenapine and methsuximide both increase sedation. Use Caution/Monitor.methylergonovineMonitor Closely (1)methylergonovine, 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).methylphenidateMonitor Closely (1)asenapine increases toxicity of methylphenidate by pharmacodynamic antagonism. Use Caution/Monitor. Closely monitor for signs of altered clinical response to either methylphenidate or an antipsychotic when using these drugs in combination.metoclopramide intranasalSerious - Use Alternative (2)asenapine, 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. asenapine increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.metoprololMonitor Closely (2)asenapine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. asenapine and metoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.mexiletineMonitor Closely (1)asenapine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)mexiletine will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.midazolamMonitor Closely (1)asenapine and midazolam both increase sedation. Use Caution/Monitor.midazolam intranasalMonitor Closely (1)midazolam intranasal, asenapine. Either increases effects 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.midostaurinSerious - Use Alternative (1)asenapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.mifepristoneMonitor Closely (1)mifepristone, asenapine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.miglitolMonitor Closely (1)asenapine, miglitol. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.milnacipranMonitor Closely (1)milnacipran, 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).mirtazapineMonitor Closely (1)asenapine and mirtazapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.mobocertinibSerious - Use Alternative (1)mobocertinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.modafinilMinor (1)modafinil will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.moexiprilMonitor Closely (1)moexipril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.molindoneMonitor Closely (1)asenapine and molindone both increase sedation. Use Caution/Monitor.morphineMonitor Closely (1)asenapine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and morphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatemoxifloxacinSerious - Use Alternative (1)asenapine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.moxisylyteMonitor Closely (1)asenapine and moxisylyte both increase anti-hypertensive channel blocking. Use Caution/Monitor.nabumetoneMonitor Closely (1)nabumetone decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.nadololMonitor Closely (1)asenapine and nadolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.nalbuphineMonitor Closely (1)asenapine and nalbuphine both increase sedation. Use Caution/Monitor.naproxenMonitor Closely (1)naproxen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.naratriptanMonitor Closely (1)naratriptan, 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).nateglinideMonitor Closely (1)asenapine, nateglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.nebivololMonitor Closely (2)asenapine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. asenapine and nebivolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.nicardipineMonitor Closely (1)asenapine and nicardipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.nifedipineMonitor Closely (1)asenapine and nifedipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.nilotinibSerious - Use Alternative (1)asenapine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.nisoldipineMonitor Closely (1)asenapine and nisoldipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.nitrous oxideMonitor Closely (1)asenapine and nitrous oxide both increase sedation. Use Caution/Monitor.nortriptylineMonitor Closely (3)asenapine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. asenapine and nortriptyline both increase QTc interval. Use Caution/Monitor. asenapine and nortriptyline both increase sedation. Use Caution/Monitor.octreotideSerious - Use Alternative (1)asenapine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.ofloxacinSerious - Use Alternative (1)asenapine and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug.olanzapineMonitor Closely (1)asenapine and olanzapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)olanzapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.oliceridineMonitor Closely (2)oliceridine, asenapine. 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. asenapine and oliceridine both increase sedation. Use Caution/Monitor.olodaterol inhaledMonitor Closely (1)asenapine and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. Drugs that prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmiasolopatadine intranasalSerious - Use Alternative (1)asenapine 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. ondansetronSerious - Use Alternative (1)asenapine and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.opicaponeMonitor Closely (1)asenapine and opicapone both increase sedation. Use Caution/Monitor.opium tinctureMonitor Closely (1)asenapine and opium tincture both increase sedation. Use Caution/Monitor.orphenadrineMonitor Closely (1)asenapine and orphenadrine both increase sedation. Use Caution/Monitor.osilodrostatMonitor Closely (1)osilodrostat and asenapine both increase QTc interval. Use Caution/Monitor.osimertinibMonitor Closely (1)osimertinib and asenapine both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.oxaliplatinMonitor Closely (1)oxaliplatin will increase the level or effect of asenapine by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.Serious - Use Alternative (1)oxaliplatin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.oxaprozinMonitor Closely (1)oxaprozin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.oxazepamMonitor Closely (1)asenapine and oxazepam both increase sedation. Use Caution/Monitor.oxycodoneMonitor Closely (1)asenapine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequateoxymorphoneMonitor Closely (1)asenapine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and oxymorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequateozanimodMonitor Closely (1)ozanimod and asenapine both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.paliperidoneMonitor Closely (1)asenapine and paliperidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.panobinostatSerious - Use Alternative (1)asenapine and panobinostat both increase QTc interval. Avoid or Use Alternate Drug.