Zukaria

• Schizophrenia:
  Treatment of schizophrenia in adults and pediatric patients aged 13 years and older.
• Bipolar I Disorder:
• Acute treatment of manic or mixed episodes associated with Bipolar I Disorder in adults and pediatric patients aged 10 years and older.
• Maintenance treatment of Bipolar I Disorder in adults to reduce the risk of recurrence of manic or mixed episodes.
• Off-label Uses (Clinically Accepted):
• Adjunctive therapy in treatment-resistant depression (limited evidence).
• Management of other psychotic disorders in select cases under specialist supervision.

• Adults:
• Schizophrenia:
  Initial dose: 5 mg sublingually twice daily.
  May increase to 10 mg twice daily based on response and tolerability.
• Bipolar I Disorder (manic/mixed episodes):
  Initial dose: 10 mg sublingually twice daily.
  Dose may be adjusted to 5 mg twice daily depending on clinical response.
• Pediatrics:
• Schizophrenia (13–17 years): 2.5 mg to 10 mg sublingually twice daily.
• Bipolar I Disorder (10–17 years): Initial dose 2.5 mg twice daily; may be increased to 10 mg twice daily.
• Elderly:
  No specific dose adjustments; use caution due to increased sensitivity.
• Hepatic Impairment:
• Moderate impairment: reduce dose by 50%.
• Severe impairment: use not recommended.
• Renal Impairment:
  No dose adjustment recommended for mild to moderate impairment; use caution in severe impairment.
• Administration:
• Administer sublingually; do not swallow or chew tablets.
• Avoid eating or drinking for at least 10 minutes post-dose to ensure absorption.

Asenapine is a second-generation (atypical) antipsychotic that exerts its effects primarily 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. This broad receptor blockade modulates dopaminergic and serotonergic neurotransmission, which helps reduce psychotic symptoms, mood disturbances, and manic episodes, restoring neurotransmitter balance implicated in schizophrenia and bipolar disorder.

• Absorption:
  Rapid sublingual absorption; bioavailability ~35% due to extensive first-pass metabolism if swallowed.
• Distribution:
  Volume of distribution approximately 20 L; ~95% plasma protein binding.
• Metabolism:
  Extensive hepatic metabolism primarily via CYP1A2, with minor contributions from CYP3A4 and CYP2D6. Also metabolized by glucuronidation.
• Half-life:
  Approximately 24 hours.
• Excretion:
  Metabolites excreted mainly via urine (50%) and feces (40%).

• Pregnancy:
  Category C (FDA). Animal studies indicate potential risks; use only if benefits justify potential risks. Limited human data available.
• Lactation:
  Unknown if excreted in human milk; potential risk to infant. Breastfeeding not recommended during treatment.

• Atypical (Second-generation) Antipsychotic

• Known hypersensitivity to asenapine or any formulation components.
• Severe hepatic impairment (due to altered metabolism).
• Concurrent use with other medications known to prolong QT interval with caution.

• Severe allergic reactions: Anaphylaxis, angioedema, urticaria reported.
• Orthostatic hypotension and syncope: Caution in patients at risk.
• QT prolongation: Monitor in patients with cardiovascular risk factors or on concomitant QT-prolonging drugs.
• Neuroleptic malignant syndrome (NMS): Rare but serious; discontinue immediately if suspected.
• Hyperglycemia and diabetes mellitus: Monitor blood glucose regularly.
• Extrapyramidal symptoms (EPS): Including akathisia, dystonia; monitor especially during initial treatment.
• Suicidal ideation: Increased risk in pediatric and young adult patients; monitor closely.

• Common:
• Oral hypoesthesia (numbness or altered taste)
• Somnolence, dizziness
• Akathisia, extrapyramidal symptoms
• Weight gain
• Dry mouth
• Serious/Rare:
• Severe hypersensitivity reactions
• QT prolongation and cardiac arrhythmias
• Neuroleptic malignant syndrome
• Hyperglycemia, diabetic ketoacidosis
• Timing:
  Side effects often appear within the first weeks but can occur anytime during therapy.

• CYP1A2 inhibitors (e.g., fluvoxamine): Increase asenapine plasma levels; dose adjustment may be needed.
• CYP1A2 inducers (e.g., smoking, carbamazepine): May reduce asenapine effectiveness.
• Other CNS depressants: Additive sedation.
• QT-prolonging drugs: Increased risk of cardiac arrhythmias.
• Food and drink: Avoid intake for 10 minutes post-dose to prevent reduced absorption.

• Updated guidelines emphasize sublingual administration and the importance of avoiding food and drink post-dose for absorption.
• Warnings regarding hypersensitivity reactions and QT prolongation have been strengthened.
• Pediatric use approved for schizophrenia (≥13 years) and bipolar disorder (≥10 years) with appropriate monitoring.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Protect from moisture and light; keep in original blister packaging until use.
• Keep out of reach of children.
• Do not freeze.