Generic Name

Asenapine Maleate

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Classification

FDA Approved Indications

• Schizophrenia
• Bipolar I disorder (manic or mixed episodes, as part of acute treatment)

Mechanism of Action

Asenapine is a serotonin (5-HT2A/2C, 5-HT6, 5-HT7), dopamine (D1, D2, D3, D4), alpha-adrenergic, and histamine (H1, H2) receptor antagonist. Its therapeutic effects are believed to result from dopamine and serotonin receptor antagonism.

Dosage and Administration

Adult: For schizophrenia, sublingual tablet: 5 mg twice daily. Dose can be increased to 10 mg twice daily based on response and tolerability.

Pediatric: Safety and efficacy not established in pediatric patients.

Geriatric: Start at the lower end of dosing. Monitor closely. Dose adjustments may be necessary based on tolerability.

Renal Impairment: Use with caution; no specific adjustments recommended, but monitor for adverse effects.

Hepatic Impairment: Use with caution; dose adjustments may be necessary, especially in moderate to severe hepatic impairment.

Pharmacokinetics

Absorption: Rapidly absorbed with sublingual administration; bioavailability around 35% due to first-pass metabolism.

Distribution: Extensive tissue distribution; high protein binding (~89%).

Metabolism: Primarily metabolized in the liver via CYP1A2, with minor CYP3A4 involvement.

Excretion: Excreted primarily in feces (>65%) and urine (~25%).

Half Life: Approximately 24 hours.

Contraindications

• Hypersensitivity to asenapine or any component of the formulation

Precautions

• Pregnancy and lactation: Risk vs benefit assessment necessary; use only if clearly needed.
• History of QT prolongation or other cardiac conduction issues.
• Caution in patients with seizure disorder, urinary retention, or severe hypotension.

Adverse Reactions - Common

• Akathisia (Common)
• Dizziness (Common)
• Somnolence (Common)
• Extrapyramidal symptoms (Common)

Adverse Reactions - Serious

• QT prolongation / arrhythmia (Serious)
• Neuroleptic Malignant Syndrome (Serious)
• Hyperglycemia / Diabetes Mellitus (Serious)
• Increased mortality in elderly with dementia-related psychosis (Serious (Black Box Warning))

Drug-Drug Interactions

• Other QT-prolonging agents (e.g., certain antidepressants, antiarrhythmics)
• CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine) may increase asenapine levels
• CYP1A2 inducers (e.g., smoking) may decrease levels

Drug-Food Interactions

• Concomitant use with alcohol increases sedative effects and risk of orthostatic hypotension.

Drug-Herb Interactions

• St. John's Wort (may decrease efficacy)

Nursing Implications

Patient/Family Teaching

• Instruct patient to take the medication sublingually and avoid eating or drinking until the tablet dissolves.
• Report signs of hallucinations, suicidal thoughts, or severe side effects.
• Caution about potential sedation, orthostatic hypotension, and navigating activities requiring alertness.
• Avoid alcohol and CNS depressants.
• Importance of regular blood tests to monitor metabolic parameters.

Special Considerations

Black Box Warnings:

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

Genetic Factors: CYP1A2 genetic variations may affect drug metabolism.

Lab Test Interference: None noted specific to asenapine.

Overdose Management

Signs/Symptoms: Drowsiness, agitation, dizziness, tachycardia or hypotension, seizures, QT prolongation.

Treatment: Supportive care, ECG monitoring, activated charcoal if ingestion recent, supportive measures for blood pressure and heart rhythm.

Storage and Handling

Storage: Store at room temperature, away from moisture and light.

Stability: Stable until expiration date if stored properly.