Asenapine

The mechanism of action of asenapine in bipolar I disorder is unknown.

• Asenapine is indicated for: • Bipolar I disorder [see Clinical Studies (14.2)] • Acute monotherapy of manic or mixed episodes, in pediatric patients 10 to 17 years of age • Adjunctive treatment to lithium or valproate in adults Asenapine is an atypical antipsychotic indicated for ( 1 ): Bipolar I disorder o Acute monotherapy treatment of manic or mixed episodes, in pediatric patients 10 to 17 years of age o Adjunctive treatment to lithium or valproate in adultsICD-10: F31.9

• Asenapine is contraindicated in patients with: Severe hepatic impairment (Child-Pugh C) [see Specific Populations (8.7), Clinical Pharmacology (12.3)] . A history of hypersensitivity reactions to asenapine.contraindicated

Starting Dose Recommended Dose Maximum Dose Bipolar mania – pediatric patients (10 to 17 years): monotherapy ( 2.3 ) 2.5 mg sublingually twice daily 2.5 to 10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania – adults: as an adjunct to lithium or valproate ( 2.3 ) 5 mg sublingually twice daily 5 to 10 mg sublingually twice daily 10 mg sublingually twice daily • Do not swallow tablet. Asenapine sublingual tablets should be placed under the tongue and left to dissolve completely. The tablet will dissolve in saliva within seconds. Eating and drinking should be avoided for 10 minutes after administration. ( 2.1 , 17 ) 2.1 Administration Instructions Asenapine is a sublingual tablet. To ensure optimal absorption, patients should be instructed to place the tablet under the tongue and allow it to dissolve completely. The tablet will dissolve in saliva within seconds. Asenapine sublingual tablets should not be split, crushed, chewed, or swallowed [see Clinical Pharmacology (12.3)]. Patients should be instructed to not eat or drink for 10 minutes after administration [see Clinical Pharmacology (12.3)]. 2.3 Bipolar I Disorder Acute Treatment of Manic or Mixed Episodes: Monotherapy in Pediatric Patients: The recommended dose of asenapine is 2.5 mg to 10 mg twice daily in pediatric patients 10 to 17 years of age, and dose may be adjusted for individual response and tolerability. The starting dose of asenapine is 2.5 mg twice daily. After 3 days, the dose can be increased to 5 mg twice daily, and from 5 mg to 10 mg twice daily after 3 additional days.

• Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). ( 5.2 ) • Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. ( 5.3 ) • Tardive Dyskinesia: Discontinue if clinically appropriate. ( 5.4 ) • Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. ( 5.5 ) • Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. ( 5.7 ) • Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing asenapine if a clinically significant decline in WBC occurs in absence of other causative factors. ( 5.9 ) • QT Prolongation: Increases in QT interval; avoid use with drugs that also increase the QT interval and in patients with risk factors for prolonged QT interval. ( 5.10 ) • Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. ( 5.12 ) • Potential for Cognitive and Motor Impairment: Use caution when operating machinery. ( 5.13 ) 5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

The following adverse reactions are discussed in more detail in other sections of the labeling: Use in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning and Warnings and Precautions (5.1 and 5.2)] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.3)] Tardive Dyskinesia [see Warnings and Precautions (5.4)] Metabolic Changes [see Warnings and Precautions (5.5)] Hypersensitivity Reactions [see Contraindications, Warnings and Precautions (5.6)] Orthostatic Hypotension, Syncope, and other Hemodynamic Effects [see Warnings and Precautions (5.7)] Falls [see Warnings and Precautions (5.8)] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.9)] QT Interval Prolongation [see Warnings and Precautions (5.10)] Hyperprolactinemia [see Warnings and Precautions (5.11)] Seizures [see Warnings and Precautions (5.12)] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.13)] Body Temperature Regulation [see Warnings and Precautions (5.14)] Dysphagia [see Warnings and Precautions (5.15)] The most common adverse reactions (≥5% and at least twice the rate of placebo) reported during the adjunctive therapy trial in bipolar I disorder in adults were somnolence and oral hypoesthesia. The rates were lower at the 5 mg twice daily dose than the 10 mg twice daily dose for all of these most common adverse reactions. The adult information below is derived from a clinical trial database for asenapine consisting of over 5355 patients and/or healthy subjects exposed to one or more sublingual doses of asenapine.

Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 ) Pediatric Use: Safety and efficacy in the treatment of bipolar I disorder in patients less than 10 years of age have not been evaluated. ( 8.4 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to asenapine during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. Studies have not been conducted with asenapine in pregnant women. There are no available human data informing the drug-associated risk. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies.

Metabolism

Following a single 5 mg dose of asenapine, the mean C max was approximately 4 ng/mL and was observed at a mean t max of 1 hour. Elimination of asenapine is primarily through direct glucuronidation by UGT1A4 and oxidative metabolism by cytochrome P450 isoenzymes (predominantly CYP1A2).

Human Experience: In adult pre-marketing clinical studies involving more than 3350 patients and/or healthy subjects, accidental or intentional acute over dosage of asenapine was identified in 3 patients. Among these few reported cases of overdose, the highest estimated ingestion of asenapine was 400 mg. Reported adverse reactions at the highest dosage included agitation and confusion. Management of Overdosage: There is no specific antidote to asenapine. The possibility of multiple drug involvement should be considered. An electrocardiogram should be obtained and management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Consult with a Certified Poison Control Center for up-to-date guidance and advice on the management of overdosage (1-800-222-1222.) Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of asenapine-induced alpha blockade).

• Aug 13, 2009NDANDA022117Abbvie
• Oct 11, 2019NDANDA212268Hisamitsu
• Dec 10, 2020ANDAANDA205960Breckenridge
• Dec 10, 2020ANDAANDA206098Alembic
• Dec 10, 2020ANDAANDA206107Sigmapharm Labs Llc

1. 1Drug Ineffective91111%
2. 2Sedation7038.1%
3. 3Suicide Attempt6637.7%
4. 4Inappropriate Schedule Of Drug Administration5646.5%
5. 5Weight Increased5646.5%
6. 6Dyskinesia5316.2%
7. 7Dystonia5206.0%
8. 8Blood Glucose Increased4825.6%
9. 9Off Label Use4355.0%
10. 10Sexual Dysfunction4345.0%
11. 11Anosognosia4234.9%
12. 12Akathisia4164.8%
13. 13Metabolic Disorder4134.8%
14. 14Blood Prolactin Abnormal4124.8%
15. 15Disturbance In Social Behaviour4104.7%

The 10 most recently updated of 59 ClinicalTrials.gov registrations naming Asenapine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Τhe Combination of Pharmacotherapy With RECOVERYTRSGR and RECOVERYTRSBDGR.
  Active not recruiting · Phase 4 · Interventional · 84 enrolled · Dr. Stavroula Rakitzi
  NCT07047651updated 2026-05-01
• Elpipodect (MK-8189) Multiple Dose Study in Healthy Volunteers and Schizophrenia Participants (MK-8189-003)
  Completed · Phase 1 · Interventional · 55 enrolled · Merck Sharp & Dohme LLC
  NCT02181803updated 2026-04-29
• A Study to Assess Stroke Risk Among Users of Typical Versus Atypical Antipsychotics Stratified by Broad Age Group
  Completed · Observational · 1,234,412 enrolled · Janssen Research & Development, LLC
  NCT04002700updated 2025-06-25
• Efficacy and Safety of Asenapine With Placebo and Haloperidol (41023)(P05926)(COMPLETED)
  Completed · Phase 3 · Interventional · 460 enrolled · Organon and Co
  NCT00156104updated 2024-08-15
• 3-week Study of Asenapine, Olanzapine and Placebo for Treatment of Bipolar Mania (P07009)
  Completed · Phase 3 · Interventional · 489 enrolled · Organon and Co
  NCT00159796updated 2024-08-15
• 3-Week Study of Asenapine, Olanzapine and Placebo for Treatment of Bipolar Mania (P07008)
  Completed · Phase 3 · Interventional · 488 enrolled · Organon and Co
  NCT00159744updated 2024-08-15
• Efficacy and Safety of Asenapine Using an Active Control in Subjects With Schizophrenia or Schizoaffective Disorder (25517)(P05935)
  Completed · Phase 3 · Interventional · 1,225 enrolled · Organon and Co
  NCT00212784updated 2024-08-15
• An Acceptability Study of Unflavored Asenapine Versus Raspberry Flavored Asenapine in Stable Patients With a Psychotic Disorder (P07010)(COMPLETED)
  Completed · Phase 2 · Interventional · 174 enrolled · Organon and Co
  NCT00878462updated 2024-08-15
• Efficacy and Safety of Asenapine Compared With Olanzapine in Patients With Persistent Negative Symptoms of Schizophrenia (25543)(COMPLETED)(P05817)
  Completed · Phase 3 · Interventional · 481 enrolled · Organon and Co
  NCT00212836updated 2024-08-15
• Efficacy and Safety of Asenapine With Placebo and Olanzapine (41022)(P05947)
  Completed · Phase 3 · Interventional · 277 enrolled · Organon and Co
  NCT00151424updated 2024-08-15

Frequently asked questions

How does Asenapine work?

The mechanism of action of asenapine in bipolar I disorder is unknown.

What is Asenapine used for?

According to FDA labeling, Asenapine carries indications including: Asenapine is indicated for: • Bipolar I disorder [see Clinical Studies (14.2)] • Acute monotherapy of manic or mixed episodes, in pediatric patients 10 to 17 years of age • Adjunctive treatment to lithium or valproate in adults Asenapine is an atypical antipsychotic indicated for ( 1 ): Bipolar I disorder o Acute monotherapy treatment of manic or mixed episodes, in pediatric patients 10 to 17 years of age o Adjunctive treatment to lithium or valproate in adults. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Asenapine?

Asenapine is classified as Diazepines, oxazepines, thiazepines and oxepines, Atypical Antipsychotic, Unknown Cellular or Molecular Interaction.

What are the brand names for Asenapine?

Asenapine is marketed under brand names including Saphris, Secuado.

What are the contraindications for Asenapine?

Asenapine labeling lists contraindications including: Asenapine is contraindicated in patients with: Severe hepatic impairment (Child-Pugh C) [see Specific Populations (8.7), Clinical Pharmacology (12.3)] . A history of hypersensitivity reactions to asenapine.. Always consult the full prescribing information and a clinician.