have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.lemborexantlemborexant, asenapine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.lenvatinibasenapine and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.levetiracetamasenapine and levetiracetam both increase sedation. Use Caution/Monitor.levocetirizineasenapine and levocetirizine both increase sedation. Use Caution/Monitor.levomilnacipranlevomilnacipran, 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).levorphanolasenapine and levorphanol both increase sedation. Use Caution/Monitor.linezolidlinezolid, 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).liraglutideasenapine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.lisinoprillisinopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.lithiumlithium, 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).lofepramineasenapine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.lofexidineasenapine and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.loratadineasenapine and loratadine both increase sedation. Use Caution/Monitor.lorazepamasenapine and lorazepam both increase sedation. Use Caution/Monitor.lorcaserinlorcaserin, 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).lornoxicamlornoxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.loxapineasenapine and loxapine both increase sedation. Use Caution/Monitor.lumateperoneasenapine and lumateperone both increase sedation. Use Caution/Monitor.lurasidoneasenapine and lurasidone both increase sedation. Use Caution/Monitor.maprotilineasenapine and maprotiline both increase sedation. Use Caution/Monitor.maravirocmaraviroc, asenapine. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration may increase risk of orthostatic hypotension.meclizineasenapine and meclizine both increase sedation. Use Caution/Monitor.meclofenamatemeclofenamate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.mefenamic acidmefenamic acid decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.meloxicammeloxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.meperidinemeperidine, 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.meprobamateasenapine and meprobamate both increase sedation. Use Caution/Monitor.metaxaloneasenapine and metaxalone both increase sedation. Use Caution/Monitor.metforminasenapine, 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.methadonemethadone, 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).methamphetamineasenapine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.methocarbamolasenapine and methocarbamol both increase sedation. Use Caution/Monitor.methohexitalasenapine and methohexital both increase sedation. Use Caution/Monitor.methsuximideasenapine and methsuximide both increase sedation. Use Caution/Monitor.methylergonovinemethylergonovine, 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).methylphenidateasenapine 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.metoprololasenapine 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.mexiletineasenapine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.midazolamasenapine and midazolam both increase sedation. Use Caution/Monitor.midazolam intranasalmidazolam 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.mifepristonemifepristone, asenapine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.miglitolasenapine, 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.milnacipranmilnacipran, 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).mirtazapineasenapine and mirtazapine both increase sedation. Use Caution/Monitor.moexiprilmoexipril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.molindoneasenapine and molindone both increase sedation. Use Caution/Monitor.morphineasenapine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.moxisylyteasenapine and moxisylyte both increase anti-hypertensive channel blocking. Use Caution/Monitor.nabumetonenabumetone decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.nadololasenapine and nadolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.nalbuphineasenapine and nalbuphine both increase sedation. Use Caution/Monitor.naproxennaproxen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.naratriptannaratriptan, 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).nateglinideasenapine, 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.nebivololasenapine 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.nicardipineasenapine and nicardipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.nifedipineasenapine and nifedipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.nisoldipineasenapine and nisoldipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.nitrous oxideasenapine and nitrous oxide both increase sedation. Use Caution/Monitor.nortriptylineasenapine 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.olanzapineasenapine and olanzapine both increase sedation. Use Caution/Monitor.oliceridineoliceridine, 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 inhaledasenapine 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 arrhythmiasopicaponeasenapine and opicapone both increase sedation. Use Caution/Monitor.opium tinctureasenapine and opium tincture both increase sedation. Use Caution/Monitor.orphenadrineasenapine and orphenadrine both increase sedation. Use Caution/Monitor.osilodrostatosilodrostat and asenapine both increase QTc interval. Use Caution/Monitor.osimertinibosimertinib 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.oxaliplatinoxaliplatin 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.oxaprozinoxaprozin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.oxazepamasenapine and oxazepam both increase sedation. Use Caution/Monitor.oxycodoneasenapine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.oxymorphoneasenapine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.ozanimodozanimod 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.paliperidoneasenapine and paliperidone both increase sedation. Use Caution/Monitor.parecoxibparecoxib decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.paroxetineasenapine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.paroxetine, 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).pasireotideasenapine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.pefloxacinpefloxacin will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.penbutololasenapine and penbutolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.pentazocineasenapine and pentazocine both increase sedation. Use Caution/Monitor.pentobarbitalasenapine and pentobarbital both increase sedation. Use Caution/Monitor.perampanelasenapine and perampanel both increase sedation. Use Caution/Monitor.perindoprilperindopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.perphenazineasenapine and perphenazine both increase QTc interval. Use Caution/Monitor.asenapine and perphenazine both increase sedation. Use Caution/Monitor.phenelzinephenelzine, 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).pheniramineasenapine and pheniramine both increase sedation. Use Caution/Monitor.phenobarbitalasenapine and phenobarbital both increase sedation. Use Caution/Monitor.phenoxybenzamineasenapine and phenoxybenzamine both increase anti-hypertensive channel blocking. Use Caution/Monitor.phentolamineasenapine and phentolamine both increase anti-hypertensive channel blocking. Use Caution/Monitor.pimozideasenapine and pimozide both increase sedation. Use Caution/Monitor.pindololasenapine and pindolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.pioglitazoneasenapine, pioglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.piroxicampiroxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.pomalidomideasenapine and pomalidomide both increase sedation. Use Caution/Monitor.pramlintideasenapine, pramlintide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.prazosinasenapine and prazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.pregabalinasenapine and pregabalin both increase sedation. Use Caution/Monitor.primidoneasenapine and primidone both increase sedation. Use Caution/Monitor.procarbazineprocarbazine, 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).prochlorperazineasenapine and prochlorperazine both decrease QTc interval. Use Caution/Monitor.asenapine and prochlorperazine both increase sedation. Use Caution/Monitor.promethazinepromethazine, 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