may increase the risk of sedation and somnolence.sufentanilMonitor Closely (1)asenapine and sufentanil both increase sedation. Use Caution/Monitor.sufentanil SLMonitor Closely (1)asenapine and sufentanil SL both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)sufentanil SL, asenapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. 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.sulfasalazineMonitor Closely (1)sulfasalazine decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.sulindacMonitor Closely (1)sulindac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.sumatriptanMonitor Closely (1)sumatriptan, 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 intranasalMonitor Closely (1)sumatriptan 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).sunitinibSerious - Use Alternative (2)sunitinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug. asenapine and sunitinib both increase QTc interval. Avoid or Use Alternate Drug.suvorexantMonitor Closely (1)asenapine and suvorexant both increase sedation. Use Caution/Monitor.tacrolimusSerious - Use Alternative (2)tacrolimus and asenapine both increase QTc interval. Avoid or Use Alternate Drug. asenapine and tacrolimus both increase QTc interval. Avoid or Use Alternate Drug.tadalafilMonitor Closely (1)tadalafil increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.tapentadolMonitor Closely (1)asenapine and tapentadol both increase sedation. Use Caution/Monitor.tasimelteonMonitor Closely (1)asenapine and tasimelteon both increase sedation. Use Caution/Monitor.telavancinSerious - Use Alternative (1)asenapine and telavancin both increase QTc interval. Avoid or Use Alternate Drug.temazepamMonitor Closely (1)asenapine and temazepam both increase sedation. Use Caution/Monitor.terazosinMonitor Closely (1)asenapine and terazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.tetrabenazineMonitor Closely (1)asenapine and tetrabenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.thalidomideContraindicated (1)asenapine and thalidomide both increase sedation. Contraindicated.thioridazineContraindicated (1)asenapine and thioridazine both increase QTc interval. Contraindicated.Monitor Closely (1)asenapine and thioridazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.thiothixeneMonitor Closely (1)asenapine and thiothixene both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and thiothixene both increase QTc interval. Avoid or Use Alternate Drug.tiagabineMonitor Closely (1)asenapine and tiagabine both increase sedation. Use Caution/Monitor.timololMonitor Closely (2)asenapine 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.tizanidineMonitor Closely (1)asenapine and tizanidine both increase sedation. Use Caution/Monitor.Minor (1)tizanidine increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.tobacco useMinor (1)tobacco use will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.tolazamideMonitor Closely (1)asenapine, 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.tolbutamideMonitor Closely (1)asenapine, 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.tolcaponeMonitor Closely (1)asenapine and tolcapone both increase sedation. Use Caution/Monitor.tolfenamic acidMonitor Closely (1)tolfenamic acid decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.tolmetinMonitor Closely (1)tolmetin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.tolterodineMinor (1)asenapine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.topiramateMonitor Closely (1)asenapine and topiramate both increase sedation. Use Caution/Monitor.toremifeneSerious - Use Alternative (1)asenapine and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Concurrent use of toremifene with agents causing QT prolongation should be avoided. If concomitant use is required it's recommended that toremifene be interrupted. If interruption not possible, patients requiring therapy with a drug that prolongs QT should be closely monitored. ECGs should be obtained for high risk patients.tramadolMonitor Closely (1)asenapine and tramadol both increase sedation. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.trandolaprilMonitor Closely (1)trandolapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.tranylcypromineMonitor Closely (1)tranylcypromine, 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).trazodoneMonitor Closely (1)asenapine and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.treprostinilMinor (1)treprostinil increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown.triazolamMonitor Closely (1)asenapine and triazolam both increase sedation. Use Caution/Monitor.triclabendazoleMonitor Closely (1)triclabendazole and asenapine both increase QTc interval. Use Caution/Monitor.trifluoperazineMonitor Closely (1)asenapine and trifluoperazine both increase sedation. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.trimipramineMonitor Closely (1)asenapine and trimipramine both increase QTc interval. Use Caution/Monitor.triprolidineMonitor Closely (1)asenapine and triprolidine both increase sedation. Use Caution/Monitor.triptorelinSerious - Use Alternative (1)asenapine and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.tropisetronMinor (1)asenapine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.umeclidinium bromide/vilanterol inhaledSerious - Use Alternative (1)asenapine increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.valbenazineMonitor Closely (1)valbenazine and asenapine both increase QTc interval. Use Caution/Monitor.valproic acidMonitor Closely (1)asenapine and valproic acid both increase sedation. Use Caution/Monitor.vandetanibSerious - Use Alternative (1)asenapine, vandetanib. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Avoid coadministration with drugs known to prolong QT interval; if a drug known to prolong QT interval must be used, more frequent ECG monitoring is recommended.vardenafilMonitor Closely (1)vardenafil increases effects of asenapine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypotension.Serious - Use Alternative (1)asenapine and vardenafil both increase QTc interval. Avoid or Use Alternate Drug.vemurafenibSerious - Use Alternative (1)vemurafenib and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.venlafaxineMonitor Closely (1)venlafaxine, 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 venlafaxine both decrease QTc interval. Avoid or Use Alternate Drug.verapamilMonitor Closely (1)asenapine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.Minor (1)verapamil will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.vigabatrinMonitor Closely (1)asenapine and vigabatrin both increase sedation. Use Caution/Monitor.vilanterol/fluticasone furoate inhaledSerious - Use Alternative (1)asenapine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.vilazodoneMonitor Closely (1)vilazodone, 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).voclosporinMonitor Closely (1)voclosporin, asenapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.voriconazoleSerious - Use Alternative (1)asenapine and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.vorinostatSerious - Use Alternative (2)asenapine and vorinostat both increase QTc interval. Avoid or Use Alternate Drug. vorinostat and asenapine both increase QTc interval. Avoid or Use Alternate Drug.yohimbeSerious - Use Alternative (1)yohimbe increases effects of asenapine by pharmacodynamic synergism. Contraindicated.zaleplonMonitor Closely (1)asenapine and zaleplon both increase sedation. Use Caution/Monitor.ziconotideMonitor Closely (1)asenapine and ziconotide both increase sedation. Use Caution/Monitor.zileutonMinor (1)zileuton will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.ziprasidoneMonitor Closely (1)asenapine and ziprasidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zolmitriptanMonitor Closely (1)zolmitriptan, 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).zolpidemMonitor Closely (1)asenapine and zolpidem both increase sedation. Use Caution/Monitor.zonisamideMonitor Closely (1)asenapine and zonisamide both increase sedation. Use Caution/Monitor.zotepineMonitor Closely (1)asenapine and zotepine both increase anti-hypertensive channel blocking. Use Caution/Monitor. >10% Somnolence (24%) Headache (12%) Dizziness (11%) Pediatric patients Oral paraesthesia (27%) Somnolence (49%) 1-10% Extrapyramidal symptoms (EPS) other than akathisia (7%) Insomnia (6%) Weight gain (5%) Akathisia (4%) Anxiety (4%) Fatigue (4%) Oral hypoesthesia (4%) Dyspepsia (4%) Dry mouth (3%) Dysgeusia (3%) Arthralgia (3%) Toothache (3%) Depression (2%) Extremity pain (2%) Pediatric patients Nausea (6%) Abdominal pain (6%) Fatigue (9%) Increased weight (3%) Hyperinsulinemia (2%) Increased appetite (8%) Headache (9%) Dizziness (7%) Dysgeusia (6%) Akathisia (2%) Insomnia (3%) Suicidal ideation (3%) Tachycardia (1%), Glossodynia (1%), Irritability (1%), Muscle pain (1%), Increased ALT (1%), Increased AST (1%), Dehydration (1%), Myalgia (1%), Parkinsonism (1%), Anger (1%), Dysmenorrhea (1%), Rash (1%), Nasal congestion (1%), Dyspnea (1%), Oropharyngeal pain (1%) Postmarketing Reports Sublingual administration: Application site reactions including oral ulcers, blisters, peeling/sloughing, and inflammation Choking reported by patients, some of whom may have also experienced oropharyngeal muscular dysfunction or hypoesthesia Falls Black Box Warnings Not indicated for dementia-related psychosis; increased risk of death in elderly patients with dementia-related psychosis; placebo-controlled trials with other atypical antipsychotics (ie, risperidone, aripiprazole, olanzapine) showed higher incidence of cerebrovascular adverse reactions (eg, cerebrovascular accidents [CVAs], transient ischemic attacks [TIAs]), including fatalities, in comparison with placeboContraindications Known hypersensitivity Severe hepatic impairment (Child-Pugh C) Cautions Type 1 hypersensitivity reactions, including anaphylaxis and angioedema, have been reported (n=52), in several cases occurring after first dose; symptoms include anaphylaxis, angioedema, hypotension, tachycardia, tongue and laryngeal edema, difficulty breathing, wheezing, or rash Neuroleptic malignant syndrome associated with use; monitor for symptoms and discontinue if necessary Hyperglycemia (monitor patients with diabetes mellitus for worsening of glucose control); assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment Weight gain may occur; monitor weight at baseline and frequently thereafter; monitor weight in pediatric patients and assess against that expected for normal growth Hypotension and syncope, especially during initial dose titration and when increasing dose; orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medications, patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure, or conduction abnormalities), and patients with cerebrovascular disease; monitoring of orthostatic vital signs should be considered in such patients, and dose reduction considered if hypotension occurs Leukopenia, neutropenia, and agranulocytosis reported with use; perform a complete blood count (CBC) during first few months of therapy; in such patients, consider discontinuation of therapy at first sign of clinically significant decline in WBC in absence of other causative factors Concurrent use of CNS-acting drugs or alcohol may increase toxicity Use with caution in patients with a history of seizures or with conditions that potentially lower seizure threshold; conditions that lower seizure threshold may be more prevalent in patients 65 years or older Cognitive or motor impairment may occur due to CNS depression; caution patients about operating hazardous machinery, including motor vehicles, until they