Asenapine

AN D USAGE SAPHRIS is indicated for: Schizophrenia in adults Bipolar I disorder • 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 SAPHRIS is an atypical antipsychotic indicated for: Schizophrenia in adults Bipolar I disorder ○ Acute monotherapy treatment 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

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 D 2 and 5-HT 2A receptors.

2 D OSAGE AND ADMINISTRATION Starting Dose Recommended Dose Maximum Dose Schizophrenia – acute treatment in adults 5 mg sublingually twice daily 5 mg sublingually twice daily 10 mg sublingually twice daily Schizophrenia – maintenance treatment in adults 5 mg sublingually twice daily 5-10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania – adults: acute and maintenance monotherapy 5-10 mg sublingually twice daily 5-10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania –pediatric patients (10 to 17 years): monotherapy 2.5 mg sublingually twice daily 2.5-10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania – adults: as an adjunct to lithium or valproate 5 mg sublingually twice daily 5-10 mg sublingually twice daily 10 mg sublingually twice daily Do not swallow tablet.

SAPHRIS 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. Severe hepatic impairment (Child-Pugh C). Known hypersensitivity to SAPHRIS (asenapine), or to any components in the formulation.

Boxed 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. SAPHRIS ® (asenapine) is not approved for the treatment of patients with dementia-related psychosis. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis. 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.

The following adverse reactions are discussed in more detail in other sections of the labeling: Use in Elderly Patients with Dementia-Related Psychosis Neuroleptic Malignant Syndrome Tardive Dyskinesia Metabolic Changes Hypersensitivity Reactions Orthostatic Hypotension, Syncope, and other Hemodynamic Effects Falls Leukopenia, Neutropenia, and Agranulocytosis QT Interval Prolongation Hyperprolactinemia Seizures Potential for Cognitive and Motor Impairment Body Temperature Regulation Dysphagia The most common adverse reactions (≥5% and at least twice the rate of placebo) reported with acute treatment in adults with schizophrenia were akathisia, oral hypoesthesia, and somnolence. The safety profile of SAPHRIS in the maintenance treatment of schizophrenia in adults was similar to that seen with acute treatment.

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

Storage Store at 20 º C to 25 º C (68 º F to 77 º F), excursions permitted between 15 º C and 30 º C (59 º F and 86 º F).