1. Clinical Overview
Flunarizine is a selective calcium channel blocker of the diphenylpiperazine class, with potent cerebral and peripheral vasodilatory properties. It is a fluorinated derivative of cinnarizine. Its primary clinical utility in India is for the prophylaxis of migraine and management of vestibular vertigo. It acts by inhibiting calcium influx into vascular smooth muscle cells and neurons, reducing vasospasm and neuronal hyperexcitability. It also exhibits antihistaminic and antidopaminergic properties.
| Onset | Duration | Bioavailability |
|---|---|---|
| Therapeutic effects for migraine prophylaxis are typically observed within 2-4 weeks of continuous therapy. | Long duration due to extensive tissue distribution and long half-life; effects persist for weeks after discontinuation. | Approximately 80-90% following oral administration. |
2. Mechanism of Action
Flunarizine exerts its therapeutic effects through multiple mechanisms: 1) Selective blockade of voltage-gated T-type calcium channels in vascular smooth muscle and neuronal cells, preventing calcium influx. This leads to cerebral vasodilation and reduced vasospasm. 2) Inhibition of calcium overload in hypoxic cells, providing a cytoprotective effect. 3) Antagonism of dopamine D2 receptors in the chemoreceptor trigger zone (CTZ), contributing to its anti-vertigo and anti-emetic effects. 4) Antagonism of histamine H1 receptors, contributing to its sedative and vestibular suppressant properties.
3. Indications & Uses
- Prophylaxis of Migraine (with or without aura)
- Symptomatic management of Vestibular Vertigo (e.g., Ménière's disease, labyrinthine disorders)
4. Dosage & Administration
Adult Dosage: For Migraine Prophylaxis: 10 mg (two 5mg tablets) once daily at bedtime for initial therapy. Maintenance: After 2 months, may reduce to 5 mg once daily at bedtime if effective. For Vertigo: 10 mg daily at bedtime for acute control, reducing to 5 mg daily for maintenance.
Administration: Administer orally, preferably at bedtime to minimize daytime drowsiness. Can be taken with or without food. Swallow the tablet whole with a glass of water. Do not crush or chew.
5. Side Effects
Common side effects may include:
- Drowsiness, sedation
- Weight gain (increased appetite)
- Dry mouth
- Fatigue, asthenia
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Potentiated sedation, drowsiness, impaired motor skills. | Major |
| Antipsychotics (Haloperidol, Risperidone) | Increased risk of extrapyramidal symptoms (EPS) and hyperprolactinemia. | Major |
| Antidepressants (SSRIs, TCAs) | Increased risk of serotonin syndrome (theoretical) and additive CNS effects. | Moderate |
| Strong CYP2D6 Inhibitors (Paroxetine, Fluoxetine) | May increase flunarizine plasma levels, increasing toxicity risk. | Moderate |
| Antihypertensives | Potential additive hypotensive effect. | Moderate |
| Levodopa | Flunarizine may antagonize the therapeutic effect of levodopa in Parkinson's disease. | Major |
7. Patient Counselling
- DO take the medicine exactly as prescribed, usually at bedtime.
- DO inform your doctor if you have a history of depression, mood swings, or Parkinson's disease.
- DO report any unusual muscle stiffness, tremors, restlessness, or mood changes immediately.
- DONT consume alcohol while on this medication.
- DONT drive or operate heavy machinery until you know how the medicine affects you.
- DONT stop the medicine abruptly without consulting your doctor, even if you feel better for migraine.
8. Toxicology & Storage
Overdose: Symptoms are primarily an extension of side effects: Severe CNS depression (coma), marked hypotension, cardiac arrhythmias (bradycardia, QT prolongation), exacerbation of EPS (severe parkinsonism, agitation), and convulsions.
Storage: Store below 30°C. Protect from light and moisture. Keep the tablet strip/blister in the outer carton. Keep out of reach of children.