Asenapine

ASENAPINE — asenapine maleate tablet
MSN LABORATORIES PRIVATE LIMITED

1 INDICATIONS AND USAGE

Asenapine sublingual tablets are indicated for:

• Schizophrenia in adults [see Clinical Studies (14.1)]
• Bipolar I disorder [see Clinical Studies (14.2)]
  • Acute monotherapy of manic or mixed episodes, in adults and pediatric patients 10 to 17 years of age
  • Adjunctive treatment to lithium or valproate in adults
  • Maintenance monotherapy treatment in adults

2 DOSAGE AND ADMINISTRATION

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)].

2.2 Schizophrenia

The recommended dose of asenapine sublingual tablets is 5 mg given twice daily. In short-term controlled trials, there was no suggestion of added benefit with a 10 mg twice daily dose, but there was a clear increase in certain adverse reactions. If tolerated, daily dosage can be increased to 10 mg twice daily after one week. The safety of doses above 10 mg twice daily has not been evaluated in clinical studies [see Clinical Studies (14.1)].

2.3 Bipolar I Disorder

Acute Treatment of Manic or Mixed Episodes:
Monotherapy in Adults: The recommended starting and treatment dose of asenapine sublingual tablets is 5 mg to 10 mg twice daily. The safety of doses above 10 mg twice daily has not been evaluated in clinical trials [see Clinical Studies (14.2)].
Monotherapy in Pediatric Patients: The recommended dose of asenapine sublingual tablets are 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 sublingual tablets 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 sublingual tablets 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 sublingual tablets 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 sublingual tablets, whether used as monotherapy or as adjunctive therapy with lithium or valproate, it is generally recommended that responding patients continue treatment beyond the acute episode.
Maintenance Treatment of Bipolar I Disorder:
Monotherapy in Adults: Continue on the asenapine sublingual tablets dose that the patient received during stabilization (5 mg to 10 mg twice daily). Depending on the clinical response and tolerability in the individual patient, a dose of 10 mg twice daily can be decreased to 5 mg twice daily. The safety of doses above 10 mg twice daily has not been evaluated in clinical trials [see Clinical Studies (14.2)].

3 DOSAGE FORMS AND STRENGTHS

• Asenapine sublingual 5 mg tablets are round, white, uncoated tablets debossed “B” on one side and “1” on the other side.
• Asenapine sublingual 10 mg tablets are round, white, uncoated tablets debossed “B” on one side and “2” on the other side.
• Asenapine sublingual 2.5 mg tablets, black cherry flavor, are white colored, round shaped, uncoated tablets debossed with “B” on one side and “5” on the other side.
• Asenapine sublingual 5 mg tablets, black cherry flavor, are round, white, uncoated tablets debossed “B” on one side and “3” on the other side.
• Asenapine sublingual 10 mg tablets, black cherry flavor, are round, white, uncoated tablets debossed “B” on one side and “4” on the other side.

4 CONTRAINDICATIONS

Asenapine sublingual tablets are 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)].

5 Asenapine Warnings and Precautions

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. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.

[see Boxed Warning and Warnings and Precautions (5.2)].

5.2 Cerebrovascular Adverse Events, Including Stroke, In Elderly Patients with Dementia-Related Psychosis

In placebo-controlled trials in elderly subjects with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. Asenapine sublingual tablets are not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning, Warnings and Precautions (5.1)].

5.3 Neuroleptic Malignant Syndrome

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue asenapine sublingual tablets and provide intensive symptomatic treatment and monitoring.

5.4 Tardive Dyskinesia

Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs, including asenapine sublingual tablets. The risk appears to be highest among the elderly, especially elderly women, but it is not possible to predict which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

The risk of tardive dyskinesia and the likelihood that it will become irreversible increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses. It may also occur after discontinuation of treatment.

There is no known treatment for tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of tardive dyskinesia is unknown.

Given these considerations, asenapine sublingual tablets should be prescribed in a manner most likely to reduce the risk of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients: 1) who suffer from a chronic illness that is known to respond to antipsychotic drugs; and 2) for whom alternative, effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. Periodically reassess the need for continued treatment.