Approved August 13, 2009

ASENAPINE
(FDA Category 1S)

SAPHRIS(R) (Schering-Plough) is a sublingual atypical antipsychotic belonging to the chemical class of dibenzo-oxepino pyrroles

DOSING INFORMATION: For the acute treatment of schizophrenia in adults, the recommended starting and target dose is 5 mg sublingually twice daily. For the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults, the recommended starting dose is 10 mg sublingually twice daily; decreasing to 5 mg twice daily if there are side effects. Asenapine sublingual tablets must not be swallowed. The tablet should be placed under the tongue and left to dissolve completely. Eating and drinking should be avoided for 10 minutes after administration.

PHARMACOKINETICS: Following sublingual administration, asenapine is rapidly absorbed with peak plasma concentrations occurring within 0.5 to 1.5 hr. The absolute bioavailability of the 5 mg sublingual tablet is 35%, while the absolute bioavailability of asenapine when swallowed is less than 2%. Asenapine is rapidly distributed with a large Vd (20 to 25 L/kg), and is 95% bound to plasma proteins, specifically albumin and alpha 1-acid glycoprotein. Asenapine is extensively metabolized by the liver via direct glucuronidation and oxidative metabolism. In vitro studies indicate asenapine is a substrate for UGT1A4, CYP1A2 and to a lesser extent CYP3A4 and CYP2D6. Terminal half-life is approximately 24 hr and steady-state concentrations are reached within 3 days.

CAUTIONS: Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Although the causes of death in clinical trials were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that antipsychotic drugs may increase mortality. It is unclear from the observational studies to what extent these mortality findings may be attributed to the antipsychotic drug as opposed to patient characteristics. Asenapine is not approved for the treatment of patients with dementia-related psychosis. Avoid using asenapine with any drug class that is known to prolong QTc interval, and in patients with risk factors for prolonged QT interval. Dizziness, tachycardia or bradycardia, and syncope may occur early in treatment. Use caution in patients with known cardiovascular or cerebrovascular disease, and in antipsychotic-naive patients. Commonly observed adverse events included akathisia, oral hypoesthesia, dizziness, somnolence, and weight gain.

FDA APPROVED INDICATIONS: Asenapine is indicated in adults for the acute treatment of schizophrenia and the acute treatment of manic or mixed episodes associated with bipolar I disorder.