Usage
Pizotifen is prescribed for the prophylactic treatment of recurrent vascular headaches, such as migraine (with or without aura), cluster headaches, and vasomotor headaches. It is not effective for treating acute migraine attacks or tension headaches. Its pharmacological classification is serotonin antagonist with additional antihistaminic and anticholinergic properties. Pizotifen’s mechanism of action involves antagonizing serotonin, histamine, and tryptamine receptors, thereby reducing vascular permeability, inhibiting platelet aggregation, and modulating pain thresholds in the cranial blood vessels.
Alternate Names
Pizotifen is also known as pizotifen hydrogen malate (the salt form). Brand names include Sandomigran, Pizofen, Mosegor Vita (in combination with B vitamins), and Pizo-A.
How It Works
Pharmacodynamics: Pizotifen primarily acts as a serotonin (5-HT2) receptor antagonist. It also exhibits antihistaminic (H1) and anticholinergic effects, although relatively weak. These actions combine to reduce vascular permeability and inhibit the effects of vasoactive substances implicated in migraine pathogenesis. Pizotifen also appears to modulate central pain pathways.
Pharmacokinetics:
- Absorption: Pizotifen is rapidly and almost completely absorbed after oral administration, with an absorption half-life of approximately 0.5-0.8 hours.
- Metabolism: Extensively metabolized in the liver, primarily by N-glucuronidation. The major metabolite, pizotifen N-glucuronide, has a longer half-life (around 23 hours) than the parent drug (about 1 hour).
- Elimination: Primarily eliminated through renal excretion of metabolites, with less than 1% of the administered dose excreted unchanged in the urine.
Mode of Action: Pizotifen blocks 5-HT2 receptors, preventing serotonin-induced vasoconstriction in cranial blood vessels. Its antihistaminic and anticholinergic actions further contribute to vasodilation and decreased vascular permeability. Additionally, pizotifen can inhibit serotonin reuptake by platelets and interfere with tryptamine and kinin activity, further modulating the vascular and pain pathways involved in migraine.
Dosage
Standard Dosage
Adults:
Initial dose: 0.5 mg at bedtime.
Maintenance dose: 1.5 mg daily, either as a single dose at night or divided into three 0.5 mg doses throughout the day.
Maximum daily dose: 4.5 mg, with a single dose not exceeding 3 mg.
Children (2 years and above):
Initial dose: 0.5 mg at bedtime.
Maximum daily dose: 1.5 mg, given in divided doses.
Maximum single dose: 1 mg.
Children under 2 years of age: Not recommended.
Special Cases:
- Elderly Patients: No specific dosage adjustments are recommended for elderly patients, but caution is advised due to potential age-related decline in hepatic, renal, and cardiovascular function.
- Patients with Renal Impairment: Dosage adjustment may be necessary.
- Patients with Hepatic Dysfunction: Dosage adjustment may be necessary.
- Patients with Comorbid Conditions: Use with caution in patients with epilepsy, closed-angle glaucoma, or urinary retention. For obese patients, consider the potential for weight gain.
Clinical Use Cases
Pizotifen is not indicated for acute treatment of medical emergencies like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as status epilepticus or cardiac arrest. It is solely for prophylactic use in migraine and other vascular headaches.
Dosage Adjustments
Dosage adjustments may be necessary based on individual patient response, tolerability, and renal or hepatic function.
Side Effects
Common Side Effects:
Increased appetite, weight gain, drowsiness, sedation, fatigue, dry mouth, nausea, dizziness.
Rare but Serious Side Effects:
Hepatotoxicity (ranging from transaminase elevations to severe hepatitis), seizures (more frequent in patients with epilepsy), depression, anxiety, insomnia, allergic reactions (rash, urticaria), hallucinations, mood changes.
Long-Term Effects:
Weight gain, potential for tolerance development (reduced effectiveness over time).
Adverse Drug Reactions (ADR):
Hepatotoxicity, seizures, severe allergic reactions, paradoxical CNS stimulation (especially in children).
Contraindications
- Hypersensitivity to pizotifen or any of its components.
- Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapy.
- Pyloroduodenal obstruction or stenosing pyloric ulcer.
- Children under 2 years of age.
Drug Interactions
- CNS Depressants: Enhanced sedative effects with alcohol, sedatives, hypnotics, antihistamines (including some cold medications), tranquilizers, muscle relaxants, and some antidepressants.
- MAOIs: Contraindicated due to potential for prolonged and intensified anticholinergic effects.
- Cisapride: Reduced efficacy of cisapride.
- Antihypertensives (adrenergic neuron blockers): Pizotifen may antagonize their hypotensive effects.
- Drugs metabolized by N-glucuronidation: Potential for increased plasma concentrations of these drugs.
Pregnancy and Breastfeeding
Pregnancy: Limited data; use only if the potential benefit outweighs the risk. Not generally recommended during pregnancy.
Breastfeeding: Pizotifen can pass into breast milk and may harm a nursing infant. Not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Serotonin (5-HT2) receptor antagonist with antihistaminic and anticholinergic properties. Reduces vascular permeability and modulates pain pathways.
- Side Effects: Increased appetite, weight gain, drowsiness, sedation, dry mouth, nausea, dizziness. Rarely: hepatotoxicity, seizures, depression, anxiety.
- Contraindications: Hypersensitivity, concurrent MAOI use, pyloroduodenal obstruction, children under 2 years.
- Drug Interactions: CNS depressants, MAOIs, cisapride, antihypertensives.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 0.5 mg initially, up to 1.5 mg daily maintenance, maximum 4.5 mg/day. Children (2+ years): 0.5 mg initially, up to 1.5 mg/day, divided doses.
- Monitoring Parameters: Liver function tests (LFTs) with prolonged use, renal function, blood pressure, weight, visual disturbances.
Popular Combinations
Pizotifen is not typically used in combination with other migraine prophylactic drugs. However, acute migraine treatment may be necessary if breakthrough headaches occur during pizotifen therapy.
Precautions
- General Precautions: Pre-screening for allergies, glaucoma, urinary retention, epilepsy, hepatic/renal dysfunction, and metabolic disorders. Monitor for weight gain.
- Specific Populations: Avoid in children under 2 years. Use with caution in elderly patients. Not recommended during pregnancy and breastfeeding.
- Lifestyle Considerations: Avoid alcohol during therapy. May impair alertness; caution with driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pizotifen?
A: Adults: Initially 0.5 mg daily, increasing to a maintenance dose of 1.5 mg/day (single or divided doses), maximum 4.5 mg/day. Children (2+ years): Initially 0.5 mg daily, increasing to a maximum of 1.5 mg/day in divided doses.
Q2: How does Pizotifen work for migraine prevention?
A: Pizotifen blocks serotonin receptors, reduces inflammation in blood vessels, and affects pain pathways in the brain, all of which contribute to migraine prevention.
Q3: What are the most common side effects of Pizotifen?
A: Increased appetite, weight gain, drowsiness, and sedation.
Q4: Can Pizotifen be used to treat an acute migraine attack?
A: No, it is only for preventing migraines, not treating active attacks.
Q5: Are there any serious side effects I should be aware of?
A: Rarely, pizotifen can cause liver problems and seizures. Contact a healthcare professional immediately if you experience any signs of these.
Q6: Can I take Pizotifen if I am pregnant or breastfeeding?
A: It is generally not recommended during pregnancy and breastfeeding. Discuss with your doctor.
Q7: Does Pizotifen interact with any other medications?
A: Yes, it can interact with CNS depressants, MAOIs, cisapride, and some antihypertensives. Provide a complete medication list to your doctor.
Q8: What should I do if I miss a dose of Pizotifen?
A: Take the missed dose as soon as you remember, unless it is close to your next scheduled dose. Do not double the dose.
Q9: Can I stop taking Pizotifen suddenly?
A: No, abrupt discontinuation may cause “rebound headaches.” Taper the dose gradually under medical supervision.
Q10: How long does it take for Pizotifen to be effective?
A: It may take up to 4 weeks to see the full benefit of Pizotifen.
