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Asenapine

FDA Drug Information • Also known as: Asenapine, Secuado

Brand Names
Asenapine, Secuado
Drug Class
Atypical Antipsychotic [EPC]
Route
SUBLINGUAL
Dosage Form
TABLET
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: 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. Asenapine is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.1, 5.2)]. WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Asenapine is not approved for the treatment of patients with dementia-related psychosis. ( 5.1 , 5.2 )

Description

11 DESCRIPTION Asenapine sublingual tablet contains asenapine maleate which is an atypical antipsychotic that is available for sublingual administration. Asenapine belongs to the class dibenzo-oxepino pyrroles. The chemical designation is (3a RS ,12b RS )-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1 H dibenzo[2,3:6,7]oxepino[4,5- c ]pyrrole (2 Z )-2 butenedioate (1:1). Its molecular formula is C 17 H 16 ClNO⋅C 4 H 4 O 4 and its molecular weight is 401.84 (free base: 285.8). The chemical structure is: Asenapine maleate is off-white to white powder. Asenapine is supplied for sublingual administration in tablets containing 2.5-mg, 5-mg or 10-mg asenapine; inactive ingredients include butylated hydroxy anisole, butylated hydroxy toluene, low-substituted hydroxypropyl cellulose, mannitol, povidone, sodium stearyl fumarate. asenapine-structure

What Is Asenapine Used For?

1 INDICATIONS AND USAGE 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

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION 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. Pediatric patients aged 10 to 17 years appear to be more sensitive to dystonia with initial dosing with asenapine when the recommended escalation schedule is not followed [see Use in Specific Populations (8.4)] . The safety of doses greater than 10 mg twice daily has not been evaluated in clinical trials [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)] . Adjunctive Therapy in Adults: The recommended starting dose of asenapine is 5 mg twice daily when administered as adjunctive therapy with either lithium or valproate. Depending on the clinical response and tolerability in the individual patient, the dose can be increased to 10 mg twice daily. The safety of doses above 10 mg twice daily as adjunctive therapy with lithium or valproate has not been evaluated in clinical trials. For patients on asenapine, used as adjunctive therapy with lithium or valproate, it is generally recommended that responding patients continue treatment beyond the acute episode.

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS 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. A total of 1427 asenapine-treated patients were treated for at least 24 weeks and 785 asenapine-treated patients had at least 52 weeks of exposure at therapeutic doses. In a 3-week monotherapy trial, the most common adverse reactions (≥5% and at least twice the rate of placebo) reported in pediatric patients with bipolar I disorder treated with asenapine were somnolence, dizziness, dysgeusia, oral hypoesthesia, nausea, increased appetite, fatigue, and increased weight. No new major safety findings were reported from a 50-week, open-label, uncontrolled safety trial. A total of 651 pediatric patients were treated with asenapine. Of these patients, 352 pediatric patients were treated with asenapine for at least 180 days and 58 pediatric patients treated with asenapine had at least 1 year of exposure. The safety of asenapine was evaluated in 403 pediatric patients with bipolar I disorder who participated in a 3-week, placebo-controlled, double-blind trial, of whom 302 patients received asenapine at fixed doses ranging from 2.5 mg to 10 mg twice daily. The stated frequencies of adverse reactions represent the proportion of individuals who experienced a treatment-emergent adverse event of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. The most commonly observed adverse reactions (incidence ≥5% and at least twice that for placebo) were ( 6.1 ): Bipolar I Disorder Pediatric Patients (Monotherapy): somnolence, dizziness, dysgeusia, oral paresthesia, nausea, increased appetite, fatigue, increased weight.

  • Bipolar I Disorder Adults (Adjunctive): somnolence, oral hypoesthesia. To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Monotherapy in Pediatric Patients with Bipolar Mania: The following findings are based on a 3-week , placebo-controlled trial for bipolar mania in which asenapine was administered at doses of 2.5 mg, 5 mg, or 10 mg twice daily. Adverse...

    • Drug Interactions

    7 DRUG INTERACTIONS

  • Antihypertensive Drugs: Asenapine may cause hypotension. ( 5.7 , 7.1 , 12.3 )
  • Paroxetine (CYP2D6 substrate and inhibitor): Reduce paroxetine by half when used in combination with asenapine. ( 7.1 , 12.3 ) 7.1 Drugs Having Clinically Important Drug Interactions with Asenapine Table 12: Clinically Important Drug Interactions with Asenapine Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Antihypertensive Drugs Because of its α 1 -adrenergic antagonism with potential for inducing hypotension, asenapine may enhance the effects of certain antihypertensive agents [see Warnings and Precautions (5.7)] . Monitor blood pressure and adjust dosage of antihypertensive drug accordingly. Strong CYP1A2 Inhibitors (e.g., Fluvoxamine) Asenapine is metabolized by CYP1A2. Marginal increase of asenapine exposure was observed when asenapine is used with fluvoxamine at 25 mg administered twice daily [see Clinical Pharmacology (12.3)] . However, the tested fluvoxamine dose was suboptimal. Full therapeutic dose of fluvoxamine is expected to cause a greater increase in asenapine exposure. Dosage reduction for asenapine based on clinical response may be necessary. CYP2D6 substrates and inhibitors (e.g., paroxetine) Asenapine may enhance the inhibitory effects of paroxetine on its own metabolism. Concomitant use of paroxetine with asenapine increased the paroxetine exposure by 2-fold as compared to use paroxetine alone [see Clinical Pharmacology (12.3)]. Reduce paroxetine dose by half when paroxetine is used in combination with asenapine. 7.2 Drugs Having No Clinically Important Interactions with Asenapine No dosage adjustment of asenapine is necessary when administered concomitantly with paroxetine (see Table 12 in Drug Interactions (7.1) for paroxetine dosage adjustment), imipramine, cimetidine, valporate, lithium, or a CYP3A4 inducer (e.g., carbamazepine, phenytoin, rifampin). In addition, valproic acid and lithium pre-dose serum concentrations collected from an adjunctive therapy study were comparable between asenapine-treated patients and placebo-treated patients indicating a lack of effect of asenapine on valproic and lithium plasma levels.

    • Contraindications

    4 CONTRAINDICATIONS 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. Reactions have included anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing and rash [see Warnings and Precautions (5.6), Adverse Reactions (6)] .

  • Severe hepatic impairment (Child-Pugh C). ( 8.7 , 12.3 )
  • Known hypersensitivity to asenapine, or to any components in the formulation. ( 4 , 5.6 , 17 )

    • Pregnancy and Breastfeeding

    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. No teratogenicity was observed in animal reproduction studies with intravenous administration of asenapine to rats and rabbits during organogenesis at doses 0.7 and 0.4 times, respectively, the maximum recommended human dose (MRHD) of 10 mg sublingually twice daily. In a pre-and post-natal study in rats, intravenous administration of asenapine at doses up to 0.7 times the MRHD produced increases in post-implantation loss and early pup deaths, and decreases in subsequent pup survival and weight gain [see Data]. Advise pregnant women of the potential risk to a fetus. Clinical Considerations Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy. These symptoms have varied in severity. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal...

    Overdosage

    10 OVERDOSAGE 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). In case of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Asenapine sublingual tablets are supplied as: 2.5-mg Tablets: White to off white, round tablets debossed with ‘L’ on one side and ‘70’ on the other side. Cartons of 60 - 6 blister cards of 10 tablets each NDC 62332-544-60 Cartons of 100 - 10 blister cards of 10 tablets each NDC 62332-544-31 5-mg Tablets: White to off white, round tablets debossed with “464” on one side and plain on other side. Cartons of 60 - 6 blister cards of 10 tablets each NDC 62332-198-60 Cartons of 100 - 10 blister cards of 10 tablets each NDC 62332-198-31 10-mg Tablets: White to off white, round tablets debossed with “465” on one side and plain on other side. Cartons of 60 - 6 blister cards of 10 tablets each NDC 62332-199-60 Cartons of 100 - 10 blister cards of 10 tablets each NDC 62332-199-31 Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.