for whom alternative treatment options are inadequatefesoterodineMinor (1)asenapine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.fexinidazoleSerious - Use Alternative (1)fexinidazole and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels and/or prolong QT interval. fexofenadineMonitor Closely (1)asenapine and fexofenadine both increase sedation. Use Caution/Monitor.fingolimodSerious - Use Alternative (1)fingolimod and asenapine both increase QTc interval. Avoid or Use Alternate Drug.flecainideMonitor Closely (1)asenapine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and flecainide both increase QTc interval. Avoid or Use Alternate Drug.flibanserinMonitor Closely (2)flibanserin, 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 flibanserin both increase sedation. Use Caution/Monitor.fluconazoleContraindicated (1)asenapine and fluconazole both increase QTc interval. Contraindicated.fluoxetineMonitor Closely (2)asenapine and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely. asenapine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.fluphenazineMonitor Closely (2)asenapine and fluphenazine both increase QTc interval. Use Caution/Monitor. asenapine and fluphenazine both increase sedation. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.flurazepamMonitor Closely (1)asenapine and flurazepam both increase sedation. Use Caution/Monitor.flurbiprofenMonitor Closely (1)flurbiprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.fluvoxamineMonitor Closely (1)fluvoxamine will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Dose reduction may be necessarySerious - Use Alternative (1)asenapine and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug.foscarnetSerious - Use Alternative (1)asenapine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.fosinoprilMonitor Closely (1)fosinopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.fostemsavirMonitor Closely (1)asenapine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.frovatriptanMonitor Closely (1)frovatriptan, 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).gabapentinMonitor Closely (1)asenapine and gabapentin both increase sedation. Use Caution/Monitor.galantamineMinor (1)asenapine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.ganaxoloneMonitor Closely (1)asenapine and ganaxolone both increase sedation. Use Caution/Monitor.gemifloxacinSerious - Use Alternative (1)gemifloxacin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.gemtuzumabMonitor Closely (1)asenapine and gemtuzumab both increase QTc interval. Use Caution/Monitor.gilteritinibSerious - Use Alternative (1)gilteritinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.glasdegibSerious - Use Alternative (1)asenapine and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.glimepirideMonitor Closely (1)asenapine, glimepiride. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.glipizideMonitor Closely (1)asenapine, glipizide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.glyburideMonitor Closely (1)asenapine, glyburide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.goserelinSerious - Use Alternative (1)asenapine and goserelin both increase QTc interval. Avoid or Use Alternate Drug.granisetronSerious - Use Alternative (1)granisetron and asenapine both increase QTc interval. Avoid or Use Alternate Drug.guanfacineMonitor Closely (1)asenapine and guanfacine both increase sedation. Use Caution/Monitor.haloperidolMonitor Closely (3)asenapine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. asenapine and haloperidol both increase sedation. Use Caution/Monitor. haloperidol and asenapine both increase QTc interval. Use Caution/Monitor.histrelinSerious - Use Alternative (1)asenapine and histrelin both increase QTc interval. Avoid or Use Alternate Drug.hydrocodoneMonitor Closely (2)asenapine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone. asenapine and hydrocodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)hydrocodone, asenapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. 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.hydromorphoneMonitor Closely (1)asenapine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and hydromorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatehydroxychloroquine sulfateSerious - Use Alternative (1)hydroxychloroquine sulfate and asenapine both increase QTc interval. Avoid or Use Alternate Drug.hydroxyzineMonitor Closely (1)asenapine and hydroxyzine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)hydroxyzine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.ibuprofenMonitor Closely (1)ibuprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.ibuprofen IVMonitor Closely (1)ibuprofen IV decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.ibutilideMonitor Closely (1)asenapine and ibutilide both increase QTc interval. Use Caution/Monitor.iloperidoneMonitor Closely (3)asenapine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. iloperidone increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. asenapine and iloperidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.imidaprilMonitor Closely (1)imidapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.imipramineMonitor Closely (3)asenapine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. asenapine and imipramine both increase QTc interval. Use Caution/Monitor. asenapine and imipramine both increase sedation. Use Caution/Monitor.indacaterol, inhaledMonitor Closely (1)indacaterol, inhaled, asenapine. QTc interval. Use Caution/Monitor. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.indapamideMonitor Closely (1)asenapine and indapamide both increase QTc interval. Use Caution/Monitor.indomethacinMonitor Closely (1)indomethacin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.inotuzumabSerious - Use Alternative (1)inotuzumab and asenapine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.insulin aspartMonitor Closely (1)asenapine, insulin aspart. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.insulin degludecMonitor Closely (1)asenapine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.insulin degludec/insulin aspartMonitor Closely (1)asenapine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.insulin detemirMonitor Closely (1)asenapine, insulin detemir. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.insulin glargineMonitor Closely (1)asenapine, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.insulin glulisineMonitor Closely (1)asenapine, insulin glulisine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.insulin inhaledMonitor Closely (1)asenapine decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.insulin lisproMonitor Closely (1)asenapine, insulin lispro. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.insulin NPHMonitor Closely (1)asenapine, insulin NPH. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.isofluraneMonitor Closely (1)asenapine and isoflurane both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)isoflurane and asenapine both increase QTc interval. Avoid or Use Alternate Drug.isoniazidMinor (1)isoniazid will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.isradipineMonitor Closely (2)asenapine and isradipine both increase QTc interval. Use Caution/Monitor. asenapine and isradipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.itraconazoleSerious - Use Alternative (1)itraconazole and asenapine both increase QTc interval. Avoid or Use Alternate Drug.ivosidenibSerious - Use Alternative (1)ivosidenib and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.ketamineMonitor Closely (1)asenapine and ketamine both increase sedation. Use Caution/Monitor.ketoprofenMonitor Closely (1)ketoprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.ketorolacMonitor Closely (1)ketorolac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.ketorolac intranasalMonitor Closely (1)ketorolac intranasal decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.ketotifen, drug-eluting contact lensMonitor Closely (1)asenapine and ketotifen, drug-eluting contact lens both increase sedation. Use Caution/Monitor.labetalolMonitor Closely (1)asenapine and labetalol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.lamotrigineMonitor Closely (1)asenapine and lamotrigine both increase sedation. Use Caution/Monitor.lapatinibSerious - Use Alternative (1)asenapine and lapatinib both increase QTc interval. Avoid or Use Alternate Drug.lasmiditanMonitor Closely (1)lasmiditan, asenapine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.lefamulinSerious - Use Alternative (1)lefamulin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.lemborexantMonitor Closely (1)lemborexant, 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.lenvatinibMonitor Closely (1)asenapine and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.leuprolideSerious - Use Alternative (1)asenapine and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.levetiracetamMonitor Closely (1)asenapine and levetiracetam both increase sedation. Use Caution/Monitor.levocetirizineMonitor Closely (1)asenapine and levocetirizine both increase sedation. Use Caution/Monitor.levodopa inhaledSerious - Use Alternative (1)asenapine decreases effects of levodopa inhaled by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Atypical (2nd generation) antipsychotics inhibit dopamine D2 receptors in varying degrees (clozapine and quetiapine are lower risk). .levofloxacinSerious - Use Alternative (1)asenapine and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug.levomilnacipranMonitor Closely (1)levomilnacipran, 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).levorphanolMonitor Closely (1)asenapine and levorphanol both increase sedation. Use Caution/Monitor.linezolidMonitor Closely (1)linezolid, 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).liraglutideMonitor Closely (1)asenapine, 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.lisinoprilMonitor Closely (1)lisinopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.lithiumMonitor Closely (1)lithium, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance