asenapine (Rx)

Brand and Other Names:Saphris

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

sublingual tablet

  • 2.5mg
  • 5mg
  • 10mg

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

Dosage Forms & Strengths

sublingual tablet

  • 2.5mg
  • 5mg
  • 10mg

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

Next:

Interactions

Interaction Checker

and asenapine

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            Contraindicated (6)

            • 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.

            • thalidomide

              asenapine and thalidomide both increase sedation. Contraindicated.

            • thioridazine

              asenapine and thioridazine both increase QTc interval. Contraindicated.

            Serious - Use Alternative (141)

            • adagrasib

              adagrasib, asenapine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

            • alfentanil

              asenapine and alfentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

              asenapine and benzhydrocodone/acetaminophen both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

              asenapine and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine buccal

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

              asenapine and buprenorphine buccal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine subdermal implant

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

              asenapine and buprenorphine subdermal implant both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine transdermal

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

              asenapine and buprenorphine transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

              asenapine and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • codeine

              asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • fentanyl

              asenapine and fentanyl both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl intranasal

              asenapine and fentanyl intranasal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl iontophoretic transdermal system

              asenapine and fentanyl iontophoretic transdermal system both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl transdermal

              asenapine and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl transmucosal

              asenapine and fentanyl transmucosal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • hydromorphone

              asenapine and hydromorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

              asenapine and methadone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • morphine

              asenapine and morphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • oxycodone

              asenapine and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • oxymorphone

              asenapine and oxymorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • 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.

            • remifentanil

              asenapine and remifentanil both increase sedation. 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 (354)

            • 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.

            • acetaminophen/phenyltoloxamine

              asenapine and acetaminophen/phenyltoloxamine both increase sedation. Use Caution/Monitor.

            • acrivastine

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

            • 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).

            • alprazolam

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

            • 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.

            • amisulpride

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

            • amitriptyline

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

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

            • amlodipine

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

            • amobarbital

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

            • amoxapine

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

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

            • arformoterol

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

            • aripiprazole

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

            • asenapine transdermal

              asenapine and asenapine transdermal both increase sedation. 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.

            • avapritinib

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

            • azithromycin

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

            • baclofen

              asenapine and baclofen both increase sedation. 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.

            • brexpiprazole

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

            • brimonidine

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

            • brivaracetam

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

            • brompheniramine

              asenapine and brompheniramine both increase 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.

            • butabarbital

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

            • butalbital

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

            • butorphanol

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

            • 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.

            • carbinoxamine

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

            • cariprazine

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

            • carisoprodol

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

            • 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.

            • cetirizine

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

            • chlordiazepoxide

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

            • chloroquine

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

            • chlorpheniramine

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

            • chlorpromazine

              asenapine and chlorpromazine both increase sedation. 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.

            • chlorzoxazone

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

            • 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.

            • clemastine

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

            • 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).

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

            • 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.

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

            • clonazepam

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

            • clonidine

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

            • clorazepate

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

            • clozapine

              asenapine and clozapine both increase sedation. 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.

            • cyclobenzaprine

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

            • cyproheptadine

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

            • dantrolene

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

            • 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.

            • desflurane

              asenapine and desflurane both increase sedation. 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.

              asenapine and desipramine both increase sedation. 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).

            • dexbrompheniramine

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

            • dexchlorpheniramine

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

            • 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).

            • diazepam

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

            • 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.

            • difenoxin hcl

              asenapine and difenoxin hcl 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.

            • dimenhydrinate

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

            • diphenhydramine

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

            • diphenoxylate hcl

              asenapine and diphenoxylate hcl both increase sedation. 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.

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

            • doxylamine

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

            • droperidol

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

            • duloxetine

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

            • efavirenz

              asenapine and efavirenz both increase sedation. 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.

            • entacapone

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

            • 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.

            • estazolam

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

            • eszopiclone

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

            • ethanol

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

            • ethosuximide

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

            • ethotoin

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

            • 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.

            • felbamate

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

            • 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.

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

            • 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).

            • fexofenadine

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

            • 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).

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

            • 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.

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

            • flurazepam

              asenapine and flurazepam both increase sedation. 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).

            • gabapentin

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

            • 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.

            • guanfacine

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

            • 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.

              asenapine and haloperidol both increase sedation. 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.

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

            • hydromorphone

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

            • hydroxyzine

              asenapine and hydroxyzine both increase sedation. 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.

              asenapine and iloperidone both increase sedation. 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.

              asenapine and imipramine both increase sedation. 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.

            • isoflurane

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

            • isradipine

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

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

            • ketamine

              asenapine and ketamine both increase sedation. 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.

            • ketotifen, drug-eluting contact lens

              asenapine and ketotifen, drug-eluting contact lens both increase sedation. Use Caution/Monitor.

            • labetalol

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

            • lamotrigine

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

            • 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.

            • levetiracetam

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

            • levocetirizine

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

            • 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).

            • levorphanol

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

            • 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.

            • loratadine

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

            • lorazepam

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

            • 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.

            • loxapine

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

            • lumateperone

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

            • lurasidone

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

            • maprotiline

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

            • maraviroc

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

            • meclizine

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

            • 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).

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

            • meprobamate

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

            • metaxalone

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

            • 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.

            • methocarbamol

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

            • methohexital

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

            • methsuximide

              asenapine and methsuximide both increase sedation. 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

              asenapine and midazolam both increase sedation. 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).

            • mirtazapine

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

            • moexipril

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

            • molindone

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

            • 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.

            • nalbuphine

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

            • 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.

            • nitrous oxide

              asenapine and nitrous oxide both increase sedation. 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.

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

            • olanzapine

              asenapine and olanzapine both increase sedation. 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.

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

            • 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

            • opicapone

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

            • opium tincture

              asenapine and opium tincture both increase sedation. Use Caution/Monitor.

            • orphenadrine

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

            • 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.

            • oxazepam

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

            • 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.

            • paliperidone

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

            • 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.

            • pentazocine

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

            • pentobarbital

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

            • perampanel

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

            • 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.

              asenapine and perphenazine both increase sedation. 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).

            • pheniramine

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

            • phenobarbital

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

            • 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.

            • pimozide

              asenapine and pimozide both increase sedation. 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.

            • pomalidomide

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

            • 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.

            • pregabalin

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

            • primidone

              asenapine and primidone both increase sedation. 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.

              asenapine and prochlorperazine both increase sedation. 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).

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

            • propafenone

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

            • propofol

              asenapine and propofol both increase sedation. 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.

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

            • pyrilamine

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

            • quazepam

              asenapine and quazepam both increase sedation. 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.

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

            • 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.

            • quizartinib

              quizartinib, asenapine. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.

            • ramelteon

              asenapine and ramelteon both increase sedation. 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.

            • reserpine

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

            • 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.

            • risperidone

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

            • 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.

            • scopolamine

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

            • 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.

            • sevoflurane

              asenapine and sevoflurane both increase sedation. 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 oxybate

              asenapine and sodium oxybate both increase sedation. Use Caution/Monitor.

            • 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.

            • sufentanil

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

            • sufentanil SL

              asenapine and sufentanil SL both increase sedation. Use Caution/Monitor.

            • 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).

            • suvorexant

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

            • tadalafil

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

            • tapentadol

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

            • tasimelteon

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

            • temazepam

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

            • terazosin

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

            • tetrabenazine

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

            • thioridazine

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

            • thiothixene

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

            • tiagabine

              asenapine and tiagabine both increase sedation. 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.

            • tizanidine

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

            • 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.

            • tolcapone

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

            • 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.

            • topiramate

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

            • tramadol

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

            • 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).

            • trazodone

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

            • triazolam

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

            • triclabendazole

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

            • trifluoperazine

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

            • trimipramine

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

            • triprolidine

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

            • valbenazine

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

            • valproic acid

              asenapine and valproic acid both increase sedation. 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.

            • vigabatrin

              asenapine and vigabatrin both increase sedation. 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.

            • zaleplon

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

            • ziconotide

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

            • ziprasidone

              asenapine and ziprasidone both increase sedation. 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).

            • zolpidem

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

            • zonisamide

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

            • 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.

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            Adverse Effects

            >10%

            Somnolence (24%)

            Headache (12%)

            Dizziness (11%)

            Pediatric patients

            • Oral paraesthesia (27%)
            • Somnolence (49%)

            1-10%

            Extrapyramidal symptoms (EPS) other than akathisia (7%)

            Insomnia (6%)

            Weight gain (5%)

            Akathisia (4%)

            Anxiety (4%)

            Fatigue (4%)

            Oral hypoesthesia (4%)

            Dyspepsia (4%)

            Dry mouth (3%)

            Dysgeusia (3%)

            Arthralgia (3%)

            Toothache (3%)

            Depression (2%)

            Extremity pain (2%)

            Pediatric patients

            • Nausea (6%)
            • Abdominal pain (6%)
            • Fatigue (9%)
            • Increased weight (3%)
            • Hyperinsulinemia (2%)
            • Increased appetite (8%)
            • Headache (9%)
            • Dizziness (7%)
            • Dysgeusia (6%)
            • Akathisia (2%)
            • Insomnia (3%)
            • Suicidal ideation (3%)
            • Tachycardia (1%), Glossodynia (1%), Irritability (1%), Muscle pain (1%), Increased ALT (1%), Increased AST (1%), Dehydration (1%), Myalgia (1%), Parkinsonism (1%), Anger (1%), Dysmenorrhea (1%), Rash (1%), Nasal congestion (1%), Dyspnea (1%), Oropharyngeal pain (1%)

            Postmarketing Reports

            Sublingual administration: Application site reactions including oral ulcers, blisters, peeling/sloughing, and inflammation

            Choking reported by patients, some of whom may have also experienced oropharyngeal muscular dysfunction or hypoesthesia

            Falls

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            Warnings

            Black Box Warnings

            Not indicated for dementia-related psychosis; increased risk of death in elderly patients with dementia-related psychosis; placebo-controlled trials with other atypical antipsychotics (ie, risperidone, aripiprazole, olanzapine) showed higher incidence of cerebrovascular adverse reactions (eg, cerebrovascular accidents [CVAs], transient ischemic attacks [TIAs]), including fatalities, in comparison with placebo

            Contraindications

            Known hypersensitivity

            Severe hepatic impairment (Child-Pugh C)

            Cautions

            Type 1 hypersensitivity reactions, including anaphylaxis and angioedema, have been reported (n=52), in several cases occurring after first dose; symptoms include anaphylaxis, angioedema, hypotension, tachycardia, tongue and laryngeal edema, difficulty breathing, wheezing, or rash

            Neuroleptic malignant syndrome associated with use; monitor for symptoms and discontinue if necessary

            Hyperglycemia (monitor patients with diabetes mellitus for worsening of glucose control); assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment

            Weight gain may occur; monitor weight at baseline and frequently thereafter; monitor weight in pediatric patients and assess against that expected for normal growth

            Hypotension and syncope, especially during initial dose titration and when increasing dose; orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medications, patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure, or conduction abnormalities), and patients with cerebrovascular disease; monitoring of orthostatic vital signs should be considered in such patients, and dose reduction considered if hypotension occurs

            Leukopenia, neutropenia, and agranulocytosis reported with use; perform a complete blood count (CBC) during first few months of therapy; in such patients, consider discontinuation of therapy at first sign of clinically significant decline in WBC in absence of other causative factors

            Concurrent use of CNS-acting drugs or alcohol may increase toxicity

            Use with caution in patients with a history of seizures or with conditions that potentially lower seizure threshold; conditions that lower seizure threshold may be more prevalent in patients 65 years or older

            Cognitive or motor impairment may occur due to CNS depression; caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy does not affect them adversely

            Dysphagia, dysmotility, and aspiration may occur; use cautiously in patients at risk for aspiration

            Potential disruption of body temperature regulation; strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to elevation in core body temperature; use with caution in patient who may experience these conditions

            Not recommended with severe hepatic impairment (Child-Pugh class C)

            Inherent suicide risk with population treated warrants close supervision when drug therapy is changed

            Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and body weight gain, which may increase cardiovascular/ cerebrovascular risk; all of the drugs in the class have been shown to produce some metabolic changes but each drug has its own specific risk profile

            Monitor weight gain in pediatric patients and assess against that expected for normal growth

            Can elevate prolactin levels, and elevation can persist during chronic administration; hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion; this, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients

            Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medications

            May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy

            Extrapyramidal symptoms, including acute dystonic reactions, pseudoparkinsonism, akathisia, and tardive dyskinesia reported

            QT prolongation

            • Based on clinical trials, therapy should be avoided in combination with other drugs known to prolong QTc including Class 1A antiarrhythmics (eg, quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), antipsychotic medications (eg, ziprasidone, chlorpromazine, thioridazine), and antibiotics (eg, gatifloxacin, moxifloxacin)
            • Treatment should also be avoided in patients with a history of cardiac arrhythmias and in other circumstances that may increase risk of occurrence of torsade de pointes and/or sudden death in association with use of drugs that prolong QTc interval, including bradycardia; hypokalemia or hypomagnesemia; and presence of congenital prolongation of QT interval

            Tardive dyskinesia

            • Risk of tardive dyskinesia and likelihood that it will become irreversible increase with duration of treatment and cumulative dose
            • Syndrome can develop after a relatively brief treatment period, even at low doses; may also occur after discontinuation of treatment; prescribe in a manner most likely to reduce risk of tardive dyskinesia
            • Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that is known to respond to antipsychotic drugs and for whom alternative, effective, but potentially less harmful treatments are not available or appropriate; some patients may require treatment despite presence of syndrome
            • In patients who do require chronic treatment, use lowest dose and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued treatment
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            Pregnancy & Lactation

            Pregnancy category: C

            Neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for EPS or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU unit support and prolonged hospitalization

            Lactation: Excretion in milk unknown; use with caution

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Mechanism of action unknown; efficacy thought to be mediated via combined antagonist activity at dopamine D2 and serotonin type 2 (5-HT2) receptors

            Absorption

            Bioavailability: SL, 35%; swallowed, ≤2%

            Peak plasma time: 0.5-1.5 hr

            Peak plasma concentration: 4 ng/mL

            Distribution

            Protein bound: 95%

            Vd: 20-25 L/kg

            Metabolism

            Metabolized by UGT1A4 and CYP450 (predominantly isoenzyme 1A2)

            Enzymes inhibited: CYP2D6 (weakly)

            Elimination

            Half-life: 24 hr

            Clearance: 52 L/hr

            Excretion: Urine (50%), feces (40%)

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            Administration

            Instructions

            Sublingual tablet; to allow optimal absorption, place under tongue and allow to dissolve completely (dissolves within seconds)

            Do not chew, split, crush, or swallow sublingual tablet

            Do not eat or drink for at least 10 minutes after administration

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            asenapine sublingual
            -
            10 mg tablet
            asenapine sublingual
            -
            2.5 mg tablet
            asenapine sublingual
            -
            10 mg tablet
            Saphris sublingual
            -
            2.5 mg tablet
            Saphris sublingual
            -
            10 mg tablet
            Saphris sublingual
            -
            5 mg tablet
            Saphris sublingual
            -
            10 mg tablet
            Saphris sublingual
            -
            10 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            asenapine sublingual

            ASENAPINE - SUBLINGUAL

            (a-SEN-a-peen)

            COMMON BRAND NAME(S): Saphris

            WARNING: There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.If you are using asenapine in combination with other medication to treat depression, also carefully read the drug information for the other medication.

            USES: This medication is used to treat certain mental/mood disorders (such as schizophrenia, bipolar disorder). Asenapine helps you to think more clearly, feel less nervous, and take part in everyday life. It may also help to decrease hallucinations (hearing/seeing things that are not there) and prevent severe mood swings. Asenapine is a psychiatric medication that belongs to the class of drugs called atypical antipsychotics. It works by helping to restore the balance of certain natural substances in the brain (neurotransmitters).

            HOW TO USE: Take this medication as directed by your doctor, usually 2 times a day. Gently remove the medication from the packaging with dry hands by peeling back the tab. Do not push the tablet through the packaging. Place your dose of this medication under the tongue and allow it to dissolve completely in your saliva. Do not chew, crush, split, or swallow the tablet whole. Do not eat or drink anything for 10 minutes after taking this medication.The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Take this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day. It may take several weeks before you get the full benefit of this drug.Keep taking this medication even if you feel well. Do not increase your dose or take this drug more often than prescribed. Your condition will not improve any faster, and your risk of side effects will increase. Do not stop taking this medication without consulting your doctor.Tell your doctor if your condition does not improve or if it worsens.

            SIDE EFFECTS: Drowsiness, dizziness, lightheadedness, and weight gain may occur. Numbness/tingling of the mouth may also occur but usually goes away within 1 hour. Sores, blisters, or pain under the tongue may rarely occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Dizziness and lightheadedness can increase the risk of falling. Get up slowly when rising from a sitting or lying position.This drug may cause muscle/nervous system problems (extrapyramidal symptoms-EPS). Your doctor may prescribe another medication to decrease these side effects. Tell your doctor right away if you notice any of the following side effects: feelings of anxiety/agitation/jitteriness, drooling/trouble swallowing, restlessness/constant need to move, shaking (tremor), shuffling walk, stiff muscles, severe muscle spasms/cramping (such as twisting neck, arching back, eyes rolling up), mask-like expression of the face.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Rarely, this medication may cause face/muscle twitching and uncontrollable movements (tardive dyskinesia). In some cases, this condition may be permanent. Tell your doctor right away if you develop any uncontrollable movements such as lip smacking, mouth puckering, tongue thrusting, chewing, or unusual arm/leg movements.This drug may rarely make your blood sugar rise, which can cause or worsen diabetes. Weight gain from this drug may increase the risk of this side effect. Tell your doctor right away if you have symptoms of high blood sugar such as increased thirst/urination. If you already have diabetes, check your blood sugar regularly as directed and share the results with your doctor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.In rare cases, asenapine may increase your level of a certain substance made by the body (prolactin). For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor right away.Rarely, with similar drugs, males may have a painful or prolonged erection lasting 4 or more hours. If this occurs, stop using this drug and get medical help right away, or permanent problems could occur.Tell your doctor right away if you have any serious side effects, including: interrupted breathing during sleep (sleep apnea), signs of infection (such as sore throat that doesn't go away, fever).Get medical help right away if you have any very serious side effects, including: severe dizziness, fainting, slow heartbeat, seizures.This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, signs of kidney problems (such as change in the amount of urine).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: See also Warning section.Before taking asenapine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems, heart problems (such as past heart attack, angina, abnormal heart rhythm), stroke, diabetes (including family history), obesity, low blood pressure, seizures, low white blood cell count, dehydration, breast cancer, substance use disorder (such as overuse of or addiction to drugs/alcohol), Alzheimer's disease, dementia, trouble swallowing, breathing trouble during sleep (sleep apnea).Asenapine may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using asenapine, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using asenapine safely.This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication may make you sweat less, making you more likely to get heat stroke. Avoid doing things that may cause you to overheat, such as hard work or exercise in hot weather, or using hot tubs. When the weather is hot, drink a lot of fluids and dress lightly. If you overheat, quickly look for a place to cool down and rest. Get medical help right away if you have a fever that does not go away, mental/mood changes, headache, or dizziness.Older adults may be more sensitive to the side effects of this drug, especially drowsiness, dizziness, lightheadedness, and QT prolongation (see above). Drowsiness, dizziness, and lightheadedness can increase the risk of falling.During pregnancy, this medication should be used only when clearly needed. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn especially during their first month, tell the doctor right away.Since untreated mental/mood problems (such as schizophrenia, bipolar disorder, depression) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Asenapine can slow down the removal of other medications from your body, which may affect how they work. One example is paroxetine, among others.Tell your doctor or pharmacist if you are taking other products that cause drowsiness such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe drowsiness/deep sleep, agitation, confusion, fainting.

            NOTES: Do not share this medication with others.Lab and/or medical tests (such as weight, blood sugar, blood pressure, complete blood counts, cholesterol/triglyceride levels) should be done while you are using this medication. Keep all medical and lab appointments.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised February 2022. Copyright(c) 2023 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.