Generic Name

Asenapine

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Classification

FDA Approved Indications

• Schizophrenia
• Bipolar I disorder (manic or mixed episodes, as monotherapy or adjunctive therapy)

Mechanism of Action

Asenapine exerts its antipsychotic effects primarily by antagonizing dopamine D2 and serotonin 5-HT2A receptors, along with activity at other serotonergic, adrenergic, and histaminergic receptors, contributing to its efficacy and side effect profile.

Dosage and Administration

Adult: Initially, 10 mg twice daily; dose may be titrated based on response and tolerability, up to 20 mg twice daily.

Pediatric: Not approved for pediatric use; safety and efficacy not established.

Geriatric: Use with caution; starting dose typically lower and titrate carefully due to increased sensitivity.

Renal Impairment: No specific dosage adjustment recommended; monitor closely.

Hepatic Impairment: Use with caution; consider starting at lower doses due to possible decreased metabolism.

Pharmacokinetics

Absorption: Rapidly absorbed orally, with peak plasma concentrations in approximately 0.5–1 hour.

Distribution: Widely distributed; plasma protein binding approximately 89%.

Metabolism: Extensively metabolized in the liver primarily via CYP1A2, with minor contributions from CYP2D6 and CYP3A4.

Excretion: Metabolites excreted mainly in urine and feces.

Half Life: Approximately 24 hours.

Contraindications

• Hypersensitivity to asenapine or excipients

Precautions

• History of QT prolongation or cardiovascular disease
• Seizure disorder
• Orthostatic hypotension
• Elderly patients with dementia-related psychosis (risk of death)
• Use with caution in hepatic impairment

Adverse Reactions - Common

• Akathisia (Common)
• Sedation (Common)
• Somnolence (Common)
• Dizziness (Common)
• Weight gain (Common)

Adverse Reactions - Serious

• QT prolongation (Serious)
• Neuroleptic malignant syndrome (Serious)
• Hyperglycemia/Diabetes Mellitus (Serious)
• Orthostatic hypotension (Serious)
• Seizures (Serious)

Drug-Drug Interactions

• CYP1A2 inhibitors (e.g., fluvoxamine) can increase asenapine levels
• CYP1A2 inducers (e.g., smoking) can decrease levels
• Other QT prolonging agents

Drug-Food Interactions

• Caffeine may reduce plasma concentrations

Drug-Herb Interactions

• St. John's Wort may decrease plasma levels

Nursing Implications

Patient/Family Teaching

• Take medication exactly as prescribed; do not alter dose without consulting healthcare provider.
• Be aware of side effects such as drowsiness, dizziness, and movement disorders.
• Report signs of metabolic changes like significant weight gain, increased thirst, or urination.
• Caution about orthostatic hypotension and risk of falls.
• Limit alcohol intake and avoid other CNS depressants unless approved.

Special Considerations

Black Box Warnings:

• Elderly patients with dementia-related psychosis treated with antipsychotics are at increased risk of death.

Genetic Factors: CYP1A2 polymorphisms may influence plasma levels.

Lab Test Interference: No significant interference reported.

Overdose Management

Signs/Symptoms: Drowsiness, agitation, extrapyramidal symptoms, tachycardia, hypotension, QT prolongation.

Treatment: Supportive care, ECG monitoring, activated charcoal if early, and appropriate symptomatic treatment.

Storage and Handling

Storage: Store at room temperature, 20°C to 25°C (68°F to 77°F).

Stability: Stable until expiration date when stored properly.