Antigrain

• Approved Indications:
• Prophylaxis of migraine headaches in adults and children aged 5 years and older.
• Prevention and treatment of cluster headaches.
• Off-label/Clinically Accepted Uses:
• Occasionally used in other types of vascular headaches.
• Sometimes employed in cyclic vomiting syndrome under specialist supervision.

• Route: Oral (tablets or syrup).
• Adults:
• Initial dose: 0.5 mg to 1 mg once daily at bedtime.
• Maintenance dose: 1.5 mg to 3 mg per day, divided into two or three doses.
• Maximum dose: Generally up to 4.5 mg daily.
• Pediatrics (≥5 years):
• Start with 0.5 mg daily at bedtime.
• May be increased gradually to a maximum of 1.5 mg daily based on response and tolerability.
• Elderly:
• Start with lower doses and monitor closely; adjust as needed.
• Renal/Hepatic impairment:
• Use with caution in severe hepatic impairment; no formal dose adjustments recommended.
• Duration:
• Treatment is usually long-term and effectiveness should be assessed after several weeks.

Pizotifen is a serotonin (5-HT2) receptor antagonist with additional antihistaminic and anticholinergic effects. It blocks 5-HT2 receptors involved in vasodilation and neurotransmitter release that contribute to migraine and cluster headache pathogenesis. By inhibiting serotonin-induced vasodilation and platelet aggregation, pizotifen reduces headache frequency. Its antihistamine and anticholinergic properties contribute to sedation and modulation of central neurotransmission.

• Absorption: Well absorbed orally; peak plasma levels in 2–3 hours.
• Distribution: Widely distributed; crosses blood-brain barrier; large volume of distribution.
• Metabolism: Extensive hepatic metabolism via CYP2D6 enzymes.
• Elimination: Excreted primarily as metabolites in urine and feces.
• Half-life: Approximately 22–30 hours.
• Onset of action: Therapeutic effects typically seen after 1–2 weeks.

• Pregnancy: Category C — animal studies show adverse effects; human data are insufficient. Use only if benefits justify risks.
• Lactation: Unknown if excreted in human milk; caution advised. Breastfeeding is generally not recommended during therapy.

• Serotonin (5-HT2) receptor antagonist
• Antimigraine agent
• Antihistamine and anticholinergic agent

• Hypersensitivity to pizotifen or excipients.
• Severe hepatic impairment.
• Angle-closure glaucoma.
• Use cautiously in patients with cardiovascular disease or urinary retention.

• May cause sedation and drowsiness; caution when driving or operating machinery.
• Monitor for weight gain due to increased appetite.
• May worsen urinary retention and glaucoma.
• Use cautiously in patients with depression or seizure disorders.
• Avoid abrupt withdrawal to prevent rebound headaches.
• Regular monitoring recommended during prolonged therapy.

• Common:
• Drowsiness, fatigue, sedation
• Increased appetite, weight gain
• Dry mouth, dizziness
• Less common/rare:
• Gastrointestinal upset (nausea, constipation)
• Blurred vision
• Urinary retention
• Mood changes, depression
• Side effects are usually dose-dependent and may decrease with continued use.

• Additive CNS depression with alcohol, benzodiazepines, and other sedatives.
• Possible increased risk of serotonin syndrome with other serotonergic drugs.
• CYP2D6 inhibitors (e.g., fluoxetine) may raise plasma pizotifen levels.
• Enhanced anticholinergic effects when combined with other anticholinergic agents.
• Caution with monoamine oxidase inhibitors (MAOIs).

• Pizotifen remains a recommended prophylactic agent for migraines and cluster headaches, especially when beta-blockers or calcium channel blockers are unsuitable.
• Recent guidelines emphasize monitoring metabolic side effects like weight gain.
• No major recent changes in dosing or indications.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in tightly closed original container.
• Do not freeze.
• Keep out of reach of children.