Asenapine

Asenapine is indicated for:

• Schizophrenia in adults
• Bipolar I disorder

The mechanism of action of asenapine, in schizophrenia and bipolar I disorder, is unknown. It has been suggested that the efficacy of asenapine in schizophrenia could be mediated through a combination of antagonist activity at D2 and 5-HT 2A receptors.

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. Patients should be instructed to not eat or drink for 10 minutes after administration.

Schizophrenia: The recommended dose of Asenapine 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.

Bipolar I Disorder: Acute Treatment of Manic or Mixed Episodes:

• Monotherapy in Adults: The recommended starting and treatment dose of Asenapine is 5 mg to 10 mg twice daily. The safety of doses above 10 mg twice daily has not been evaluated in clinical trials.
• 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. The safety of doses greater than 10 mg twice daily has not been evaluated in clinical trials.
• 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, 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.

Bipolar I Disorder: Maintenance Treatment of Bipolar I Disorder:

• Monotherapy in Adults: Continue on the Asenapine 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.

Antihypertensive Drugs: Asenapine may cause hypotension.
Paroxetine (CYP2D6 substrate and inhibitor): Reduce paroxetine by half when used in combination with Asenapine.

Asenapine is contraindicated in patients with:

• Severe hepatic impairment (Child-Pugh C).
• A history of hypersensitivity reactions to asenapine. Reactions have included anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing and rash.

The most commonly observed adverse reactions (incidence ≥5% and at least twice that for placebo) were:

• Schizophrenia Adults: akathisia, oral hypoesthesia, somnolence.
• Bipolar I Disorder Adults (Monotherapy): somnolence, oral hypoesthesia, dizziness, extrapyramidal symptoms (excluding akathisia) and akathisia.
• 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.

May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure.

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack).

Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring.

Tardive Dyskinesia: Discontinue if clinically appropriate.

Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain.

Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope.

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 SAPHRIS if a clinically significant decline in WBC occurs in absence of other causative factors.

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.

Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: Use caution when operating machinery.

Keep below 30ºC temperature, protected from light & moisture. Keep out of the reach of children.