Asenapine

Asenapine is a second-generation (atypical) antipsychotic used for the treatment of schizophrenia in adults and for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults and pediatric patients aged 10-17 years.

Asenapine should be placed under the tongue and allowed to dissolve completely. It should not be chewed, crushed, or swallowed. Eating and drinking should be avoided for 10 minutes after administration.

Asenapine works by blocking dopamine D2 and serotonin 5-HT2A receptors in the brain. Common side effects include akathisia, somnolence, oral hypoesthesia, dizziness, and weight gain.

• 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.

Asenapine blocks dopamine D2 and serotonin 5-HT2A receptors in the brain. This receptor blockade restores the balance of dopamine and serotonin neurotransmission, which helps control the positive and negative symptoms of schizophrenia and manic episodes in bipolar disorder.

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.

Place the tablet under the tongue and allow it to dissolve completely. Do not chew, crush, or swallow the tablet. Do not eat or drink for at least 10 minutes after administration.

If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.

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.

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.

• Severe hepatic impairment (Child-Pugh C)
• Known hypersensitivity to asenapine or any component (anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, rash)

• Antihypertensive drugs: Asenapine may cause hypotension; use with caution
• Paroxetine (CYP2D6 substrate and inhibitor): Reduce paroxetine dose by half when used with asenapine
• Drugs that prolong QT interval: Avoid concomitant use with other QT-prolonging drugs including Class 1A antiarrhythmics

No specific food restrictions. However, do not eat or drink for 10 minutes after sublingual administration.

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

[CONSULT YOUR DOCTOR] It is unknown whether asenapine is excreted in human milk. Breastfeeding is not recommended during treatment.

Bipolar I disorder in pediatric patients 10-17 years: 2.5-10 mg sublingually twice daily. Initial dose 2.5 mg twice daily, titrated gradually.

Schizophrenia in patients 13-17 years: 2.5-10 mg twice daily. Safety and efficacy in patients under 10 years (bipolar) and under 12 years (schizophrenia) have not been established.

Elderly patients with dementia-related psychosis have an increased risk of death; asenapine is not approved for this population.

Hepatic Impairment: Moderate impairment: reduce dose by 50%; severe impairment (Child-Pugh C): contraindicated.

Renal Impairment: No dose adjustment needed for mild to moderate impairment; use caution in severe 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.

Asenapine Maleate