Zukaria 5

• Schizophrenia in adults
• Acute treatment of manic or mixed episodes in bipolar I disorder (adults and pediatric patients 10-17 years)
• Maintenance treatment of bipolar I disorder in adults
• Adjunctive treatment to lithium or valproate in adults

Asenapine is a second-generation (atypical) antipsychotic that exerts its effects by antagonizing multiple neurotransmitter receptors in the brain. It has high affinity for serotonin receptors (5-HT2A, 5-HT2C, 5-HT6, 5-HT7), dopamine receptors (D2, D3), alpha-adrenergic receptors (α1, α2), and histamine H1 receptors.

Asenapine modulates dopaminergic and serotonergic neurotransmission, which helps reduce psychotic symptoms, mood disturbances, and manic episodes in schizophrenia and bipolar disorder. Preclinical studies have shown that asenapine increases dopamine, norepinephrine, and acetylcholine levels in cortical and limbic brain areas.

Adults - Schizophrenia: 5 mg sublingually twice daily. May be increased to 10 mg twice daily after one week.

Adults - Bipolar Mania (Monotherapy): 5-10 mg sublingually twice daily.

Adults - Bipolar Mania (Adjunctive): 5 mg sublingually twice daily; may increase to 10 mg twice daily.

Pediatric (10-17 years) - Bipolar Mania: 2.5 mg sublingually twice daily (initial). May increase to 5 mg after 3 days and to 10 mg after 3 more days.

Hepatic Impairment: Moderate impairment: reduce dose by 50%; severe impairment (Child-Pugh C): not recommended.

Renal Impairment: No dose adjustment needed for mild to moderate impairment.

Common Adverse Reactions (≥5% and at least twice placebo):

• Akathisia
• Somnolence
• Oral hypoesthesia/dysgeusia
• Dizziness
• Extrapyramidal symptoms (EPS)
• Nausea
• Increased appetite
• Fatigue
• Weight gain

Serious Adverse Reactions: Neuroleptic malignant syndrome (NMS), tardive dyskinesia, metabolic changes (hyperglycemia, dyslipidemia), orthostatic hypotension, leukopenia, neutropenia, agranulocytosis, seizures.

[CONSULT YOUR DOCTOR] Limited data on asenapine use in pregnancy (Category C). Third trimester exposure may cause extrapyramidal and/or withdrawal symptoms in neonates.

Serious Precautions:

• Elderly patients with dementia-related psychosis have an increased risk of death; asenapine is not approved for this population.
• If neuroleptic malignant syndrome (NMS) is suspected, discontinue immediately.
• If tardive dyskinesia occurs, discontinue if clinically appropriate.
• Monitor for metabolic changes - regular blood glucose and lipid testing.
• Orthostatic hypotension - caution in patients with cardiovascular or cerebrovascular disease.
• QT prolongation risk - avoid use with drugs that prolong QT interval.
• Caution in patients with a history of seizures.
• Caution when operating machinery - may cause somnolence and cognitive impairment.

There is no specific antidote for asenapine. Management should focus on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and symptom management. In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision should continue until the patient recovers.

Do not store above 30°C. Keep away from light and out of reach of children.