asenapine (Rx)

Schizophrenia

5 mg SL q12hr initially; maintenance: after 1 week, may be increased up to 10 mg PO q12hr

Bipolar Disorder

Manic or mixed episodes associated with bipolar I disorder, either as monotherapy or as adjunct to lithium or valproate

Monotherapy: 10 mg PO q12hr initially; may be decreased to 5 mg PO q12hr on day 2 and subsequent days if warranted by adverse effects or individual tolerance (90% of patients typically remain on higher dose)

Adjunct to lithium or valproate: 5 mg PO q12hr initially; may be increased to 10 mg PO q12hr if warranted

If patient responds favorably, continue beyond initial acute phase (no recommendations at this time for duration of therapy)

Dosage Modifications

Renal impairment

• Dose adjustment not necessary

Hepatic impairment

• Mild to moderate impairment (Child-Pugh class A or B): Dose adjustment not necessary
• Severe impairment (Child-Pugh class C): Contraindicated

Bipolar Disorder

Indicated as monotherapy for acute treatment of manic or mixed episodes associated with bipolar I disorder

<10 years: Safety and efficacy not established

10-17 years: 2.5 SL q12hr initially; may increase to 5 mg SL q12hr after 3 days and to 10 mg SL q12hr after 3 additional days

Dosing Considerations

Pediatric patients are more sensitive to dystonia with initial dosing when recommended escalation schedule not followed

Safety and efficacy of doses >10 mg q12hr not established

Not indicated for dementia-related psychosis, in view of increased risk of death as compared with placebo (see Black Box Warnings)

In elderly patients with psychosis, asenapine exposure (area under curve [AUC]) was on average 40% higher than in younger adults

Contraindicated (5)

• amisulpride

  amisulpride, asenapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndrome.

• dronedarone

  asenapine and dronedarone both increase QTc interval. Contraindicated.

• fluconazole

  asenapine and fluconazole both increase QTc interval. Contraindicated.

• posaconazole

  asenapine and posaconazole both increase QTc interval. Contraindicated.

• thioridazine

  asenapine and thioridazine both increase QTc interval. Contraindicated.

Serious - Use Alternative (124)

• alfuzosin

  alfuzosin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• amiodarone

  asenapine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

  amisulpride and asenapine both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• anagrelide

  anagrelide and asenapine both increase QTc interval. Avoid or Use Alternate Drug.
  
  asenapine and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.

• apomorphine

  apomorphine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• aripiprazole

  aripiprazole and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• arsenic trioxide

  asenapine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  artemether and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  asenapine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• atomoxetine

  atomoxetine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, 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.

• buprenorphine

  asenapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• ceritinib

  ceritinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• chlorpromazine

  asenapine and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

  clarithromycin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• clozapine

  clozapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• dasatinib

  dasatinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• degarelix

  degarelix and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• desflurane

  desflurane and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• disopyramide

  asenapine and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

• dofetilide

  dofetilide increases toxicity of asenapine by QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  dolasetron and asenapine both decrease QTc interval. Avoid or Use Alternate Drug.

• donepezil

  donepezil and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• droperidol

  asenapine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

• efavirenz

  efavirenz and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• eliglustat

  asenapine and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.

• encorafenib

  encorafenib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

  asenapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

• eribulin

  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 base

  asenapine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  asenapine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  asenapine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  asenapine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  escitalopram increases toxicity of asenapine by QTc interval. Avoid or Use Alternate Drug.

• fexinidazole

  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.

• fingolimod

  fingolimod and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• flecainide

  asenapine and flecainide both increase QTc interval. Avoid or Use Alternate Drug.

• fluvoxamine

  asenapine and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug.

• foscarnet

  asenapine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

• gemifloxacin

  gemifloxacin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• gilteritinib

  gilteritinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• glasdegib

  asenapine and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

• goserelin

  asenapine and goserelin both increase QTc interval. Avoid or Use Alternate Drug.

• granisetron

  granisetron and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• histrelin

  asenapine and histrelin both increase QTc interval. Avoid or Use Alternate Drug.

• hydrocodone

  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.

• hydroxychloroquine sulfate

  hydroxychloroquine sulfate and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyzine

  hydroxyzine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• iloperidone

  asenapine and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.

• inotuzumab

  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.

• isoflurane

  isoflurane and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• itraconazole

  itraconazole and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  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.

• lapatinib

  asenapine and lapatinib both increase QTc interval. Avoid or Use Alternate Drug.

• lefamulin

  lefamulin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• leuprolide

  asenapine and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.

• levodopa inhaled

  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). .

• levofloxacin

  asenapine and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• lithium

  lithium and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• loperamide

  asenapine and loperamide both increase QTc interval. Avoid or Use Alternate Drug.

• lopinavir

  asenapine and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

• macimorelin

  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.

• maprotiline

  asenapine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.

• mefloquine

  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.

• methadone

  asenapine and methadone both increase QTc interval. Avoid or Use Alternate Drug.

• metoclopramide intranasal

  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.

• midostaurin

  asenapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

• mirtazapine

  mirtazapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• mobocertinib

  mobocertinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

• moxifloxacin

  asenapine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• nilotinib

  asenapine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide

  asenapine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  asenapine and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• olanzapine

  olanzapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• olopatadine intranasal

  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.

• ondansetron

  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.

• oxaliplatin

  oxaliplatin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• paliperidone

  asenapine and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.

• panobinostat

  asenapine and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. Panobinostat is known to significantly prolong QT interval. Panobinostat prescribing information states use with drugs known to prolong QTc is not recommended.

• paroxetine

  asenapine and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.

• pazopanib

  asenapine and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

• pentamidine

  asenapine and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

• pimavanserin

  pimavanserin and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• pimozide

  asenapine and pimozide both increase QTc interval. Contraindicated.

• pitolisant

  asenapine and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

• ponesimod

  asenapine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

• primaquine

  primaquine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• procainamide

  asenapine and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

• promethazine

  asenapine and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• propafenone

  asenapine and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

• quinidine

  asenapine and quinidine both increase QTc interval. Avoid or Use Alternate Drug.

• ranolazine

  asenapine and ranolazine both increase QTc interval. Avoid or Use Alternate Drug.

• ribociclib

  ribociclib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• risperidone

  asenapine and risperidone both increase QTc interval. Avoid or Use Alternate Drug.

• romidepsin

  asenapine and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.

• safinamide

  asenapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

• saquinavir

  saquinavir, asenapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of QT prolongation and cardiac arrhythmias.
  
  asenapine and saquinavir both increase QTc interval. Avoid or Use Alternate Drug.

• selinexor

  selinexor, asenapine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• sertraline

  sertraline and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• sevoflurane

  sevoflurane and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• sildenafil

  sildenafil increases effects of asenapine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of hypotension; separate sildenafil >25mg from alpha blocker by 4hr.

• siponimod

  siponimod and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• solifenacin

  solifenacin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• sotalol

  asenapine and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

• sufentanil SL

  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.

• sunitinib

  sunitinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.
  
  asenapine and sunitinib both increase QTc interval. Avoid or Use Alternate Drug.

• tacrolimus

  tacrolimus and asenapine both increase QTc interval. Avoid or Use Alternate Drug.
  
  asenapine and tacrolimus both increase QTc interval. Avoid or Use Alternate Drug.

• telavancin

  asenapine and telavancin both increase QTc interval. Avoid or Use Alternate Drug.

• tetrabenazine

  asenapine and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

• thioridazine

  asenapine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• thiothixene

  asenapine and thiothixene both increase QTc interval. Avoid or Use Alternate Drug.

• toremifene

  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.

• trazodone

  asenapine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

• triptorelin

  asenapine and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.

• umeclidinium bromide/vilanterol inhaled

  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.

• vandetanib

  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.

• vardenafil

  asenapine and vardenafil both increase QTc interval. Avoid or Use Alternate Drug.

• vemurafenib

  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.

• venlafaxine

  asenapine and venlafaxine both decrease QTc interval. Avoid or Use Alternate Drug.

• vilanterol/fluticasone furoate inhaled

  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.

• voriconazole

  asenapine and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.

• vorinostat

  asenapine and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.
  
  vorinostat and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• yohimbe

  yohimbe increases effects of asenapine by pharmacodynamic synergism. Contraindicated.

• ziprasidone

  asenapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

Monitor Closely (225)

• acarbose

  asenapine, acarbose. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• acebutolol

  asenapine and acebutolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• aceclofenac

  aceclofenac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• acemetacin

  acemetacin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• albiglutide

  asenapine, albiglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• albuterol

  albuterol and asenapine both increase QTc interval. Use Caution/Monitor.

• aldesleukin

  aldesleukin increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• alfuzosin

  alfuzosin and asenapine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• almotriptan

  almotriptan, 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).

• amifostine

  amifostine, asenapine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.
  
  amifostine, asenapine. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Due to its alpha adrenergic antagonism, atypical antipsychotic agents has the potential to enhance the effect of certain antihypertensive agents. Monitor blood pressure and adjust dose accordingly.

• amitriptyline

  asenapine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• amlodipine

  asenapine and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• amoxapine

  asenapine and amoxapine both increase QTc interval. Use Caution/Monitor.

• arformoterol

  arformoterol and asenapine both increase QTc interval. Use Caution/Monitor.

• aspirin

  aspirin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• aspirin rectal

  aspirin rectal decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• aspirin/citric acid/sodium bicarbonate

  aspirin/citric acid/sodium bicarbonate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• atenolol

  asenapine and atenolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• atomoxetine

  asenapine will increase the level or effect of atomoxetine by Other (see comment). Use Caution/Monitor. Potential for enhanced CNS depression. Monitor closely during conurrent use.

• avanafil

  avanafil increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• azithromycin

  azithromycin increases toxicity of asenapine by QTc interval. Use Caution/Monitor.

• bedaquiline

  asenapine and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

• benazepril

  benazepril increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• benzhydrocodone/acetaminophen

  asenapine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

• betaxolol

  asenapine and betaxolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• bisoprolol

  asenapine and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• brexanolone

  brexanolone, asenapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• buprenorphine, long-acting injection

  asenapine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

• captopril

  captopril, asenapine. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

• carbidopa

  carbidopa increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Monitor for hypotension.

• carvedilol

  asenapine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and carvedilol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• celecoxib

  celecoxib decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• celiprolol

  asenapine and celiprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• cenobamate

  cenobamate, asenapine. Either increases effects of the other by sedation. Use Caution/Monitor.

• chloroquine

  chloroquine increases toxicity of asenapine by QTc interval. Use Caution/Monitor.

• chlorpropamide

  asenapine, chlorpropamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• choline magnesium trisalicylate

  choline magnesium trisalicylate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• ciprofloxacin

  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.

• citalopram

  asenapine and citalopram both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

• clevidipine

  asenapine and clevidipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• clobazam

  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).

• clomipramine

  asenapine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and clomipramine both increase QTc interval. Use Caution/Monitor.

• crizotinib

  crizotinib and asenapine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

• daridorexant

  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.

• deferasirox

  deferasirox increases levels of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• desipramine

  asenapine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and desipramine both increase QTc interval. Use Caution/Monitor.

• deutetrabenazine

  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.
  
  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).

• dextromethorphan

  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).

• diclofenac

  diclofenac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• difelikefalin

  difelikefalin and asenapine both increase sedation. Use Caution/Monitor.

• diflunisal

  diflunisal decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• dihydroergotamine

  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).

• diltiazem

  asenapine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• doxazosin

  asenapine and doxazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• doxepin

  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.

• duloxetine

  asenapine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• eletriptan

  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).

• enalapril

  enalapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• ergoloid mesylates

  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).

• ergotamine

  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).

• esketamine intranasal

  esketamine intranasal, asenapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• esmolol

  asenapine and esmolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• etodolac

  etodolac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• exenatide injectable solution

  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 suspension

  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.

• ezogabine

  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.

• felodipine

  asenapine and felodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• fenfluramine

  asenapine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.

• fenoprofen

  fenoprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• fentanyl

  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).

• flecainide

  asenapine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• flibanserin

  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).

• fluoxetine

  asenapine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.

• fluphenazine

  asenapine and fluphenazine both increase QTc interval. Use Caution/Monitor.

• flurbiprofen

  flurbiprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• fluvoxamine

  fluvoxamine will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Dose reduction may be necessary

• fosinopril

  fosinopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• fostemsavir

  asenapine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

  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).

• ganaxolone

  asenapine and ganaxolone both increase sedation. Use Caution/Monitor.

• gemtuzumab

  asenapine and gemtuzumab both increase QTc interval. Use Caution/Monitor.

• glimepiride

  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.

• glipizide

  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.

• glyburide

  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.

• haloperidol

  asenapine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  haloperidol and asenapine both increase QTc interval. Use Caution/Monitor.

• hydrocodone

  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.

• hydromorphone

  asenapine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• ibuprofen

  ibuprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• ibuprofen IV

  ibuprofen IV decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• ibutilide

  asenapine and ibutilide both increase QTc interval. Use Caution/Monitor.

• iloperidone

  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.

• imidapril

  imidapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• imipramine

  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.

• indacaterol, inhaled

  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.

• indapamide

  asenapine and indapamide both increase QTc interval. Use Caution/Monitor.

• indomethacin

  indomethacin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• insulin aspart

  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 degludec

  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 aspart

  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 detemir

  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 glargine

  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 glulisine

  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 inhaled

  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 lispro

  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 NPH

  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.

• isradipine

  asenapine and isradipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
  
  asenapine and isradipine both increase QTc interval. Use Caution/Monitor.

• ketoprofen

  ketoprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• ketorolac

  ketorolac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• ketorolac intranasal

  ketorolac intranasal decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• labetalol

  asenapine and labetalol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• lasmiditan

  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.

• lemborexant

  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.

• lenvatinib

  asenapine and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.

• levomilnacipran

  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).

• linezolid

  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).

• liraglutide

  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.

• lisinopril

  lisinopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• lithium

  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 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).

• lofepramine

  asenapine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lofexidine

  asenapine and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.

• lorcaserin

  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).

• lornoxicam

  lornoxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• maraviroc

  maraviroc, asenapine. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration may increase risk of orthostatic hypotension.

• meclofenamate

  meclofenamate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• mefenamic acid

  mefenamic acid decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• meloxicam

  meloxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• meperidine

  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).

• metformin

  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.

• methadone

  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).

• methamphetamine

  asenapine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• methylergonovine

  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).

• methylphenidate

  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.

• metoprolol

  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.

• mexiletine

  asenapine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• midazolam intranasal

  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.

• mifepristone

  mifepristone, asenapine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

• miglitol

  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.

• milnacipran

  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).

• moexipril

  moexipril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• morphine

  asenapine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• moxisylyte

  asenapine and moxisylyte both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nabumetone

  nabumetone decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• nadolol

  asenapine and nadolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• naproxen

  naproxen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• naratriptan

  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).

• nateglinide

  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.

• nebivolol

  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.

• nicardipine

  asenapine and nicardipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nifedipine

  asenapine and nifedipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nisoldipine

  asenapine and nisoldipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nortriptyline

  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.

• oliceridine

  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.

• olodaterol inhaled

  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 arrhythmias

• osilodrostat

  osilodrostat and asenapine both increase QTc interval. Use Caution/Monitor.

• osimertinib

  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.

• oxaliplatin

  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.

• oxaprozin

  oxaprozin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• oxycodone

  asenapine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• oxymorphone

  asenapine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• ozanimod

  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.

• parecoxib

  parecoxib decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• paroxetine

  asenapine 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).

• pasireotide

  asenapine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

• pefloxacin

  pefloxacin will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• penbutolol

  asenapine and penbutolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• perindopril

  perindopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• perphenazine

  asenapine and perphenazine both increase QTc interval. Use Caution/Monitor.

• phenelzine

  phenelzine, 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).

• phenoxybenzamine

  asenapine and phenoxybenzamine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• phentolamine

  asenapine and phentolamine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• pindolol

  asenapine and pindolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• pioglitazone

  asenapine, 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.

• piroxicam

  piroxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• pramlintide

  asenapine, 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.

• prazosin

  asenapine and prazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• procarbazine

  procarbazine, 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).

• prochlorperazine

  asenapine and prochlorperazine both decrease QTc interval. Use Caution/Monitor.

• promethazine

  promethazine, 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).

• propafenone

  asenapine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• propranolol

  asenapine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and propranolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• protriptyline

  asenapine and protriptyline both increase QTc interval. Use Caution/Monitor.

• quetiapine

  quetiapine, asenapine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.

• quinapril

  quinapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• quinine

  asenapine and quinine both increase QTc interval. Use Caution/Monitor.

• ramipril

  ramipril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• remimazolam

  remimazolam, asenapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• repaglinide

  asenapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• rifampin

  rifampin will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• rilpivirine

  rilpivirine increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

• rosiglitazone

  asenapine, rosiglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• salicylates (non-asa)

  salicylates (non-asa) decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• salsalate

  salsalate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• saxagliptin

  asenapine, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• selegiline

  selegiline, 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).

• selpercatinib

  selpercatinib increases toxicity of asenapine by QTc interval. Use Caution/Monitor.

• silodosin

  asenapine and silodosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• sitagliptin

  asenapine, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• sodium sulfate/?magnesium sulfate/potassium chloride

  sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.
  
  sodium sulfate/?magnesium sulfate/potassium chloride increases effects of asenapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• sodium sulfate/potassium sulfate/magnesium sulfate

  sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.
  
  sodium sulfate/potassium sulfate/magnesium sulfate increases effects of asenapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• sorafenib

  sorafenib and asenapine both increase QTc interval. Use Caution/Monitor.

• sotalol

  asenapine and sotalol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• stiripentol

  stiripentol, asenapine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• sulfasalazine

  sulfasalazine decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• sulindac

  sulindac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• sumatriptan

  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 intranasal

  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).

• tadalafil

  tadalafil increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• terazosin

  asenapine and terazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• timolol

  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.

• tolazamide

  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.

• tolbutamide

  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.

• tolfenamic acid

  tolfenamic acid decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• tolmetin

  tolmetin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• trandolapril

  trandolapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• tranylcypromine

  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).

• triclabendazole

  triclabendazole and asenapine both increase QTc interval. Use Caution/Monitor.

• trimipramine

  asenapine and trimipramine both increase QTc interval. Use Caution/Monitor.

• valbenazine

  valbenazine and asenapine both increase QTc interval. Use Caution/Monitor.

• vardenafil

  vardenafil increases effects of asenapine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypotension.

• venlafaxine

  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).

• verapamil

  asenapine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• vilazodone

  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).

• voclosporin

  voclosporin, asenapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• zolmitriptan

  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).

• zotepine

  asenapine and zotepine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

Minor (54)

• amobarbital

  amobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• aripiprazole

  asenapine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• armodafinil

  armodafinil will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• brimonidine

  brimonidine increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown.

• butabarbital

  butabarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• butalbital

  butalbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• butcher's broom

  asenapine, butcher's broom. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• carbamazepine

  carbamazepine will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• chlorpromazine

  asenapine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• cigarette smoking

  cigarette smoking will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• cimetidine

  cimetidine will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• codeine

  asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dexfenfluramine

  asenapine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextroamphetamine

  asenapine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextromethorphan

  asenapine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• donepezil

  asenapine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• encainide

  asenapine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• erythromycin base

  erythromycin base will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ethanol

  asenapine, ethanol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension, esp. in Asian pts.

• ethinylestradiol

  ethinylestradiol will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• fesoterodine

  asenapine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• fluphenazine

  asenapine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• galantamine

  asenapine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• isoniazid

  isoniazid will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• loratadine

  asenapine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• mexiletine

  mexiletine will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• modafinil

  modafinil will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• peginterferon alfa 2a

  peginterferon alfa 2a will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• pentobarbital

  pentobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• perhexiline

  asenapine will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• perphenazine

  asenapine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• phenobarbital

  phenobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• phenylephrine

  asenapine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• phenylephrine PO

  asenapine, phenylephrine PO. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• pipemidic acid

  pipemidic acid will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• primidone

  primidone will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• prochlorperazine

  asenapine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promazine

  asenapine will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promethazine

  asenapine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• risperidone

  asenapine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• secobarbital

  secobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• smoking

  smoking will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• tizanidine

  tizanidine increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

• tobacco use

  tobacco use will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• tolterodine

  asenapine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tramadol

  asenapine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• treprostinil

  treprostinil increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown.

• trifluoperazine

  asenapine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tropisetron

  asenapine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• verapamil

  verapamil will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• zileuton

  zileuton will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• acarbose

  Monitor Closely (1)asenapine, acarbose. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• acebutolol

  Monitor Closely (1)asenapine and acebutolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• aceclofenac

  Monitor Closely (1)aceclofenac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• acemetacin

  Monitor Closely (1)acemetacin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• albiglutide

  Monitor Closely (1)asenapine, albiglutide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• albuterol

  Monitor Closely (1)albuterol and asenapine both increase QTc interval. Use Caution/Monitor.

• aldesleukin

  Monitor Closely (1)aldesleukin increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• alfuzosin

  Monitor Closely (1)alfuzosin and asenapine both increase anti-hypertensive channel blocking. Use Caution/Monitor.Serious - Use Alternative (1)alfuzosin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• almotriptan

  Monitor Closely (1)almotriptan, 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).

• amifostine

  Monitor Closely (2)amifostine, asenapine. Either increases effects of the other by anti-hypertensive channel blocking. Use Caution/Monitor. Due to its alpha adrenergic antagonism, atypical antipsychotic agents has the potential to enhance the effect of certain antihypertensive agents. Monitor blood pressure and adjust dose accordingly.
  
  amifostine, asenapine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

• amiodarone

  Serious - Use Alternative (1)asenapine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

  Contraindicated (1)amisulpride, asenapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndrome.Serious - Use Alternative (1)amisulpride and asenapine both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• amitriptyline

  Monitor Closely (1)asenapine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• amlodipine

  Monitor Closely (1)asenapine and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• amobarbital

  Minor (1)amobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• amoxapine

  Monitor Closely (1)asenapine and amoxapine both increase QTc interval. Use Caution/Monitor.

• anagrelide

  Serious - Use Alternative (2)anagrelide and asenapine both increase QTc interval. Avoid or Use Alternate Drug.
  
  asenapine and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.

• apomorphine

  Serious - Use Alternative (1)apomorphine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• arformoterol

  Monitor Closely (1)arformoterol and asenapine both increase QTc interval. Use Caution/Monitor.

• aripiprazole

  Serious - Use Alternative (1)aripiprazole and asenapine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)asenapine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• armodafinil

  Minor (1)armodafinil will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• arsenic trioxide

  Serious - Use Alternative (1)asenapine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  Serious - Use Alternative (1)artemether and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Serious - Use Alternative (1)asenapine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• aspirin

  Monitor Closely (1)aspirin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• aspirin rectal

  Monitor Closely (1)aspirin rectal decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• aspirin/citric acid/sodium bicarbonate

  Monitor Closely (1)aspirin/citric acid/sodium bicarbonate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• atenolol

  Monitor Closely (1)asenapine and atenolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• atomoxetine

  Monitor Closely (1)asenapine will increase the level or effect of atomoxetine by Other (see comment). Use Caution/Monitor. Potential for enhanced CNS depression. Monitor closely during conurrent use.Serious - Use Alternative (1)atomoxetine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• avanafil

  Monitor Closely (1)avanafil increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• azithromycin

  Monitor Closely (1)azithromycin increases toxicity of asenapine by QTc interval. Use Caution/Monitor.

• bedaquiline

  Monitor Closely (1)asenapine and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

• benazepril

  Monitor Closely (1)benazepril increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)asenapine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.Serious - Use Alternative (1)benzhydrocodone/acetaminophen, 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.

• betaxolol

  Monitor Closely (1)asenapine and betaxolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• bisoprolol

  Monitor Closely (1)asenapine and bisoprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• brexanolone

  Monitor Closely (1)brexanolone, asenapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brimonidine

  Minor (1)brimonidine increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown.

• buprenorphine

  Serious - Use Alternative (2)asenapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine, long-acting injection

  Monitor Closely (1)asenapine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

• butabarbital

  Minor (1)butabarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• butalbital

  Minor (1)butalbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• butcher's broom

  Minor (1)asenapine, butcher's broom. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• captopril

  Monitor Closely (1)captopril, asenapine. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

• carbamazepine

  Minor (1)carbamazepine will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• carbidopa

  Monitor Closely (1)carbidopa increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Monitor for hypotension.

• carvedilol

  Monitor Closely (2)asenapine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and carvedilol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• celecoxib

  Monitor Closely (1)celecoxib decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• celiprolol

  Monitor Closely (1)asenapine and celiprolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• cenobamate

  Monitor Closely (1)cenobamate, asenapine. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  Serious - Use Alternative (1)ceritinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• chloroquine

  Monitor Closely (1)chloroquine increases toxicity of asenapine by QTc interval. Use Caution/Monitor.

• chlorpromazine

  Serious - Use Alternative (1)asenapine and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)asenapine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chlorpropamide

  Monitor Closely (1)asenapine, chlorpropamide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• choline magnesium trisalicylate

  Monitor Closely (1)choline magnesium trisalicylate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• cigarette smoking

  Minor (1)cigarette smoking will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• cimetidine

  Minor (1)cimetidine will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ciprofloxacin

  Monitor 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.

• citalopram

  Monitor 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.

• clarithromycin

  Serious - Use Alternative (1)clarithromycin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• clevidipine

  Monitor Closely (1)asenapine and clevidipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• clobazam

  Monitor Closely (1)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).

• clomipramine

  Monitor Closely (2)asenapine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and clomipramine both increase QTc interval. Use Caution/Monitor.

• clozapine

  Serious - Use Alternative (1)clozapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• codeine

  Minor (1)asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• crizotinib

  Monitor 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.

• daridorexant

  Monitor 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.

• dasatinib

  Serious - Use Alternative (1)dasatinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• deferasirox

  Monitor Closely (1)deferasirox increases levels of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• degarelix

  Serious - Use Alternative (1)degarelix and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• desflurane

  Serious - Use Alternative (1)desflurane and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• desipramine

  Monitor Closely (2)asenapine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and desipramine both increase QTc interval. Use Caution/Monitor.

• deutetrabenazine

  Monitor 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.

• dexfenfluramine

  Minor (1)asenapine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextroamphetamine

  Minor (1)asenapine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextromethorphan

  Monitor 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.

• diclofenac

  Monitor Closely (1)diclofenac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• difelikefalin

  Monitor Closely (1)difelikefalin and asenapine both increase sedation. Use Caution/Monitor.

• diflunisal

  Monitor Closely (1)diflunisal decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• dihydroergotamine

  Monitor 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).

• diltiazem

  Monitor Closely (1)asenapine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• disopyramide

  Serious - Use Alternative (1)asenapine and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

• dofetilide

  Serious - Use Alternative (1)dofetilide increases toxicity of asenapine by QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  Serious - Use Alternative (1)dolasetron and asenapine both decrease QTc interval. Avoid or Use Alternate Drug.

• donepezil

  Serious - 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.

• doxazosin

  Monitor Closely (1)asenapine and doxazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• doxepin

  Monitor Closely (2)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.

• dronedarone

  Contraindicated (1)asenapine and dronedarone both increase QTc interval. Contraindicated.

• droperidol

  Serious - Use Alternative (1)asenapine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

• duloxetine

  Monitor Closely (1)asenapine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• efavirenz

  Serious - Use Alternative (1)efavirenz and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• eletriptan

  Monitor 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).

• eliglustat

  Serious - Use Alternative (1)asenapine and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.

• enalapril

  Monitor Closely (1)enalapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• encainide

  Minor (1)asenapine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• encorafenib

  Serious - Use Alternative (1)encorafenib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

  Serious - Use Alternative (1)asenapine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

• ergoloid mesylates

  Monitor 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).

• ergotamine

  Monitor 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).

• eribulin

  Serious - 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 base

  Serious - 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 ethylsuccinate

  Serious - 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 lactobionate

  Serious - 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 stearate

  Serious - 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.

• escitalopram

  Serious - Use Alternative (1)escitalopram increases toxicity of asenapine by QTc interval. Avoid or Use Alternate Drug.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, asenapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• esmolol

  Monitor Closely (1)asenapine and esmolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• ethanol

  Minor (1)asenapine, ethanol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension, esp. in Asian pts.

• ethinylestradiol

  Minor (1)ethinylestradiol will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• etodolac

  Monitor Closely (1)etodolac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• exenatide injectable solution

  Monitor 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 suspension

  Monitor 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.

• ezogabine

  Monitor 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.

• felodipine

  Monitor Closely (1)asenapine and felodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• fenfluramine

  Monitor Closely (1)asenapine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.

• fenoprofen

  Monitor Closely (1)fenoprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• fentanyl

  Monitor 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).

• fesoterodine

  Minor (1)asenapine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• fexinidazole

  Serious - 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.

• fingolimod

  Serious - Use Alternative (1)fingolimod and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• flecainide

  Monitor 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.

• flibanserin

  Monitor Closely (1)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).

• fluconazole

  Contraindicated (1)asenapine and fluconazole both increase QTc interval. Contraindicated.

• fluoxetine

  Monitor 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.

• fluphenazine

  Monitor Closely (1)asenapine and fluphenazine both increase QTc interval. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• flurbiprofen

  Monitor Closely (1)flurbiprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• fluvoxamine

  Monitor 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.

• foscarnet

  Serious - Use Alternative (1)asenapine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

• fosinopril

  Monitor Closely (1)fosinopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• fostemsavir

  Monitor Closely (1)asenapine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

  Monitor 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).

• galantamine

  Minor (1)asenapine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ganaxolone

  Monitor Closely (1)asenapine and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

  Serious - Use Alternative (1)gemifloxacin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• gemtuzumab

  Monitor Closely (1)asenapine and gemtuzumab both increase QTc interval. Use Caution/Monitor.

• gilteritinib

  Serious - Use Alternative (1)gilteritinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• glasdegib

  Serious - 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.

• glimepiride

  Monitor 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.

• glipizide

  Monitor 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.

• glyburide

  Monitor 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.

• goserelin

  Serious - Use Alternative (1)asenapine and goserelin both increase QTc interval. Avoid or Use Alternate Drug.

• granisetron

  Serious - Use Alternative (1)granisetron and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• haloperidol

  Monitor Closely (2)asenapine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  haloperidol and asenapine both increase QTc interval. Use Caution/Monitor.

• histrelin

  Serious - Use Alternative (1)asenapine and histrelin both increase QTc interval. Avoid or Use Alternate Drug.

• hydrocodone

  Monitor Closely (1)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.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.

• hydromorphone

  Monitor Closely (1)asenapine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• hydroxychloroquine sulfate

  Serious - Use Alternative (1)hydroxychloroquine sulfate and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyzine

  Serious - Use Alternative (1)hydroxyzine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• ibuprofen

  Monitor Closely (1)ibuprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• ibuprofen IV

  Monitor Closely (1)ibuprofen IV decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• ibutilide

  Monitor Closely (1)asenapine and ibutilide both increase QTc interval. Use Caution/Monitor.

• iloperidone

  Monitor Closely (2)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.Serious - Use Alternative (1)asenapine and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.

• imidapril

  Monitor Closely (1)imidapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• imipramine

  Monitor Closely (2)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.

• indacaterol, inhaled

  Monitor 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.

• indapamide

  Monitor Closely (1)asenapine and indapamide both increase QTc interval. Use Caution/Monitor.

• indomethacin

  Monitor Closely (1)indomethacin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• inotuzumab

  Serious - 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 aspart

  Monitor 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 degludec

  Monitor 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 aspart

  Monitor 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 detemir

  Monitor 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 glargine

  Monitor 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 glulisine

  Monitor 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 inhaled

  Monitor 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 lispro

  Monitor 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 NPH

  Monitor 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.

• isoflurane

  Serious - Use Alternative (1)isoflurane and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• isoniazid

  Minor (1)isoniazid will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• isradipine

  Monitor Closely (2)asenapine and isradipine both increase QTc interval. Use Caution/Monitor.
  
  asenapine and isradipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• itraconazole

  Serious - Use Alternative (1)itraconazole and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  Serious - 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.

• ketoprofen

  Monitor Closely (1)ketoprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• ketorolac

  Monitor Closely (1)ketorolac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• ketorolac intranasal

  Monitor Closely (1)ketorolac intranasal decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• labetalol

  Monitor Closely (1)asenapine and labetalol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• lapatinib

  Serious - Use Alternative (1)asenapine and lapatinib both increase QTc interval. Avoid or Use Alternate Drug.

• lasmiditan

  Monitor 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.

• lefamulin

  Serious - Use Alternative (1)lefamulin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• lemborexant

  Monitor 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.

• lenvatinib

  Monitor 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.

• leuprolide

  Serious - Use Alternative (1)asenapine and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.

• levodopa inhaled

  Serious - 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). .

• levofloxacin

  Serious - Use Alternative (1)asenapine and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• levomilnacipran

  Monitor 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).

• linezolid

  Monitor 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).

• liraglutide

  Monitor 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.

• lisinopril

  Monitor Closely (1)lisinopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• lithium

  Monitor 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 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.

• lofepramine

  Monitor Closely (1)asenapine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lofexidine

  Monitor Closely (1)asenapine and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.

• loperamide

  Serious - Use Alternative (1)asenapine and loperamide both increase QTc interval. Avoid or Use Alternate Drug.

• lopinavir

  Serious - Use Alternative (1)asenapine and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

• loratadine

  Minor (1)asenapine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• lorcaserin

  Monitor 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).

• lornoxicam

  Monitor Closely (1)lornoxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• macimorelin

  Serious - 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.

• maprotiline

  Serious - Use Alternative (1)asenapine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.

• maraviroc

  Monitor 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.

• meclofenamate

  Monitor Closely (1)meclofenamate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• mefenamic acid

  Monitor Closely (1)mefenamic acid decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• mefloquine

  Serious - 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.

• meloxicam

  Monitor Closely (1)meloxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• meperidine

  Monitor Closely (1)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).

• metformin

  Monitor 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.

• methadone

  Monitor 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 (1)asenapine and methadone both increase QTc interval. Avoid or Use Alternate Drug.

• methamphetamine

  Monitor Closely (1)asenapine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• methylergonovine

  Monitor 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).

• methylphenidate

  Monitor 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 intranasal

  Serious - 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.

• metoprolol

  Monitor 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.

• mexiletine

  Monitor 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.

• midazolam intranasal

  Monitor 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.

• midostaurin

  Serious - Use Alternative (1)asenapine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

• mifepristone

  Monitor Closely (1)mifepristone, asenapine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

• miglitol

  Monitor 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.

• milnacipran

  Monitor 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).

• mirtazapine

  Serious - Use Alternative (1)mirtazapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• mobocertinib

  Serious - 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.

• modafinil

  Minor (1)modafinil will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• moexipril

  Monitor Closely (1)moexipril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• morphine

  Monitor Closely (1)asenapine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• moxifloxacin

  Serious - Use Alternative (1)asenapine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• moxisylyte

  Monitor Closely (1)asenapine and moxisylyte both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nabumetone

  Monitor Closely (1)nabumetone decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• nadolol

  Monitor Closely (1)asenapine and nadolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• naproxen

  Monitor Closely (1)naproxen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• naratriptan

  Monitor 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).

• nateglinide

  Monitor 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.

• nebivolol

  Monitor 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.

• nicardipine

  Monitor Closely (1)asenapine and nicardipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nifedipine

  Monitor Closely (1)asenapine and nifedipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nilotinib

  Serious - Use Alternative (1)asenapine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

• nisoldipine

  Monitor Closely (1)asenapine and nisoldipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• nortriptyline

  Monitor Closely (2)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.

• octreotide

  Serious - Use Alternative (1)asenapine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  Serious - Use Alternative (1)asenapine and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• olanzapine

  Serious - Use Alternative (1)olanzapine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• oliceridine

  Monitor Closely (1)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.

• olodaterol inhaled

  Monitor 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 arrhythmias

• olopatadine intranasal

  Serious - 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.

• ondansetron

  Serious - 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.

• osilodrostat

  Monitor Closely (1)osilodrostat and asenapine both increase QTc interval. Use Caution/Monitor.

• osimertinib

  Monitor 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.

• oxaliplatin

  Monitor 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.

• oxaprozin

  Monitor Closely (1)oxaprozin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• oxycodone

  Monitor Closely (1)asenapine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (1)asenapine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• ozanimod

  Monitor 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.

• paliperidone

  Serious - Use Alternative (1)asenapine and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.

• panobinostat

  Serious - Use Alternative (1)asenapine and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. Panobinostat is known to significantly prolong QT interval. Panobinostat prescribing information states use with drugs known to prolong QTc is not recommended.

• parecoxib

  Monitor Closely (1)parecoxib decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• paroxetine

  Monitor Closely (2)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).
  
  asenapine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.

• pasireotide

  Monitor Closely (1)asenapine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

• pazopanib

  Serious - Use Alternative (1)asenapine and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

• pefloxacin

  Monitor Closely (1)pefloxacin will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• peginterferon alfa 2a

  Minor (1)peginterferon alfa 2a will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• penbutolol

  Monitor Closely (1)asenapine and penbutolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• pentamidine

  Serious - Use Alternative (1)asenapine and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

• pentobarbital

  Minor (1)pentobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• perhexiline

  Minor (1)asenapine will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• perindopril

  Monitor Closely (1)perindopril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• perphenazine

  Monitor Closely (1)asenapine and perphenazine both increase QTc interval. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• phenelzine

  Monitor Closely (1)phenelzine, 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).

• phenobarbital

  Minor (1)phenobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• phenoxybenzamine

  Monitor Closely (1)asenapine and phenoxybenzamine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• phentolamine

  Monitor Closely (1)asenapine and phentolamine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• phenylephrine

  Minor (1)asenapine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• phenylephrine PO

  Minor (1)asenapine, phenylephrine PO. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• pimavanserin

  Serious - Use Alternative (1)pimavanserin and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.

• pimozide

  Serious - Use Alternative (1)asenapine and pimozide both increase QTc interval. Contraindicated.

• pindolol

  Monitor Closely (1)asenapine and pindolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• pioglitazone

  Monitor Closely (1)asenapine, 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.

• pipemidic acid

  Minor (1)pipemidic acid will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• piroxicam

  Monitor Closely (1)piroxicam decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• pitolisant

  Serious - Use Alternative (1)asenapine and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

• ponesimod

  Serious - Use Alternative (1)asenapine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

• posaconazole

  Contraindicated (1)asenapine and posaconazole both increase QTc interval. Contraindicated.

• pramlintide

  Monitor Closely (1)asenapine, 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.

• prazosin

  Monitor Closely (1)asenapine and prazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• primaquine

  Serious - Use Alternative (1)primaquine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• primidone

  Minor (1)primidone will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• procainamide

  Serious - Use Alternative (1)asenapine and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

• procarbazine

  Monitor Closely (1)procarbazine, 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).

• prochlorperazine

  Monitor Closely (1)asenapine and prochlorperazine both decrease QTc interval. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promazine

  Minor (1)asenapine will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promethazine

  Monitor Closely (1)promethazine, 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 promethazine both decrease QTc interval. Avoid or Use Alternate Drug.Minor (1)asenapine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• propafenone

  Monitor Closely (1)asenapine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

• propranolol

  Monitor Closely (2)asenapine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and propranolol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

• protriptyline

  Monitor Closely (1)asenapine and protriptyline both increase QTc interval. Use Caution/Monitor.

• quetiapine

  Monitor Closely (1)quetiapine, asenapine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.

• quinapril

  Monitor Closely (1)quinapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• quinidine

  Serious - Use Alternative (1)asenapine and quinidine both increase QTc interval. Avoid or Use Alternate Drug.

• quinine

  Monitor Closely (1)asenapine and quinine both increase QTc interval. Use Caution/Monitor.

• ramipril

  Monitor Closely (1)ramipril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• ranolazine

  Serious - Use Alternative (1)asenapine and ranolazine both increase QTc interval. Avoid or Use Alternate Drug.

• remimazolam

  Monitor Closely (1)remimazolam, asenapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• repaglinide

  Monitor Closely (1)asenapine, repaglinide. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• ribociclib

  Serious - Use Alternative (1)ribociclib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• rilpivirine

  Monitor Closely (1)rilpivirine increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

• risperidone

  Serious - Use Alternative (1)asenapine and risperidone both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)asenapine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• romidepsin

  Serious - Use Alternative (1)asenapine and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.

• rosiglitazone

  Monitor Closely (1)asenapine, rosiglitazone. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• safinamide

  Serious - Use Alternative (1)asenapine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

• salicylates (non-asa)

  Monitor Closely (1)salicylates (non-asa) decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• salsalate

  Monitor Closely (1)salsalate decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• saquinavir

  Serious - Use Alternative (2)saquinavir, asenapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of QT prolongation and cardiac arrhythmias.
  
  asenapine and saquinavir both increase QTc interval. Avoid or Use Alternate Drug.

• saxagliptin

  Monitor Closely (1)asenapine, saxagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• secobarbital

  Minor (1)secobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• selegiline

  Monitor Closely (1)selegiline, 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).

• selinexor

  Serious - Use Alternative (1)selinexor, asenapine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• selpercatinib

  Monitor Closely (1)selpercatinib increases toxicity of asenapine by QTc interval. Use Caution/Monitor.

• sertraline

  Serious - Use Alternative (1)sertraline and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• sevoflurane

  Serious - Use Alternative (1)sevoflurane and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• sildenafil

  Serious - Use Alternative (1)sildenafil increases effects of asenapine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of hypotension; separate sildenafil >25mg from alpha blocker by 4hr.

• silodosin

  Monitor Closely (1)asenapine and silodosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• siponimod

  Serious - Use Alternative (1)siponimod and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• sitagliptin

  Monitor Closely (1)asenapine, sitagliptin. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.

• smoking

  Minor (1)smoking will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (2)sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.
  
  sodium sulfate/?magnesium sulfate/potassium chloride increases effects of asenapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (2)sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.
  
  sodium sulfate/potassium sulfate/magnesium sulfate increases effects of asenapine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• solifenacin

  Serious - Use Alternative (1)solifenacin and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• sorafenib

  Monitor Closely (1)sorafenib and asenapine both increase QTc interval. Use Caution/Monitor.

• sotalol

  Monitor Closely (1)asenapine and sotalol both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)asenapine and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (1)stiripentol, asenapine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• sufentanil SL

  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.

• sulfasalazine

  Monitor Closely (1)sulfasalazine decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• sulindac

  Monitor Closely (1)sulindac decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• sumatriptan

  Monitor 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 intranasal

  Monitor 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).

• sunitinib

  Serious - 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.

• tacrolimus

  Serious - 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.

• tadalafil

  Monitor Closely (1)tadalafil increases effects of asenapine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• telavancin

  Serious - Use Alternative (1)asenapine and telavancin both increase QTc interval. Avoid or Use Alternate Drug.

• terazosin

  Monitor Closely (1)asenapine and terazosin both increase anti-hypertensive channel blocking. Use Caution/Monitor.

• tetrabenazine

  Serious - Use Alternative (1)asenapine and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

• thioridazine

  Contraindicated (1)asenapine and thioridazine both increase QTc interval. Contraindicated.Serious - Use Alternative (1)asenapine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• thiothixene

  Serious - Use Alternative (1)asenapine and thiothixene both increase QTc interval. Avoid or Use Alternate Drug.

• timolol

  Monitor 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.

• tizanidine

  Minor (1)tizanidine increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

• tobacco use

  Minor (1)tobacco use will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• tolazamide

  Monitor 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.

• tolbutamide

  Monitor 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.

• tolfenamic acid

  Monitor Closely (1)tolfenamic acid decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• tolmetin

  Monitor Closely (1)tolmetin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• tolterodine

  Minor (1)asenapine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• toremifene

  Serious - 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.

• tramadol

  Minor (1)asenapine will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• trandolapril

  Monitor Closely (1)trandolapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

• tranylcypromine

  Monitor 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).

• trazodone

  Serious - Use Alternative (1)asenapine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

• treprostinil

  Minor (1)treprostinil increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown.

• triclabendazole

  Monitor Closely (1)triclabendazole and asenapine both increase QTc interval. Use Caution/Monitor.

• trifluoperazine

  Minor (1)asenapine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• trimipramine

  Monitor Closely (1)asenapine and trimipramine both increase QTc interval. Use Caution/Monitor.

• triptorelin

  Serious - Use Alternative (1)asenapine and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.

• tropisetron

  Minor (1)asenapine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• umeclidinium bromide/vilanterol inhaled

  Serious - 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.

• valbenazine

  Monitor Closely (1)valbenazine and asenapine both increase QTc interval. Use Caution/Monitor.

• vandetanib

  Serious - 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.

• vardenafil

  Monitor 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.

• vemurafenib

  Serious - 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.

• venlafaxine

  Monitor 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.

• verapamil

  Monitor 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.

• vilanterol/fluticasone furoate inhaled

  Serious - 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.

• vilazodone

  Monitor 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).

• voclosporin

  Monitor Closely (1)voclosporin, asenapine. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• voriconazole

  Serious - Use Alternative (1)asenapine and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.

• vorinostat

  Serious - 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.

• yohimbe

  Serious - Use Alternative (1)yohimbe increases effects of asenapine by pharmacodynamic synergism. Contraindicated.

• zileuton

  Minor (1)zileuton will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ziprasidone

  Serious - Use Alternative (1)asenapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

• zolmitriptan

  Monitor 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).

• zotepine

  Monitor Closely (1)asenapine and zotepine both increase anti-hypertensive channel blocking. Use Caution/Monitor.