Usage
Flunarizine is prescribed for the prophylaxis of migraine headaches, particularly in cases where other preventive treatments have been unsuccessful. It is also used to treat vestibular disorders (e.g., vertigo, dizziness). Its pharmacological classifications include calcium channel blocker, selective calcium entry blocker, and piperazine derivative.
Flunarizine’s mechanism of action involves blocking calcium channels in vascular smooth muscle, inhibiting calcium influx into cells, and stabilizing cell membranes. This action prevents excessive vasoconstriction and vasodilation, believed to contribute to migraine development. Additionally, it possesses some antihistaminic properties.
Alternate Names
Flunarizine dihydrochloride is the chemical name. Brand names include Sibelium, Flurizin, and Flunarin. Previously, it was marketed under Apo-Flunarizine in Canada. As of February 16th, 2025, Apo-Flunarizine is no longer available in Canada.
How It Works
Pharmacodynamics: Flunarizine primarily acts as a calcium channel blocker, preferentially affecting the cerebral vasculature. It inhibits calcium influx into vascular smooth muscle cells, leading to vasodilation and improved cerebral blood flow. This action also helps prevent the excessive arterial and arteriolar spasms thought to be associated with migraine attacks. Flunarizine does not alleviate acute migraine attacks.
Pharmacokinetics: Flunarizine is well-absorbed orally, reaching peak plasma concentrations in 2-4 hours. It has high protein binding (99%). The elimination half-life is highly variable, ranging from 5-15 hours in most individuals, but some may have measurable plasma concentrations for up to 30 days. Metabolism is primarily hepatic, with less than 6% of the administered dose excreted in feces and less than 1% in urine within the first 48 hours. The terminal elimination half-life is 19 days.
Mode of Action: Flunarizine selectively blocks calcium entry into cells via slow channels. This reduces intracellular calcium levels in vascular smooth muscle, inhibiting vasoconstriction. While its exact mechanism in migraine prevention is not fully elucidated, it’s believed to involve preventing excessive vasodilation of cerebral blood vessels.
Receptor Binding, Enzyme Inhibition or Neurotransmitter Modulation: Flunarizine predominantly interacts with calcium channels, although the specific subtypes are not fully characterized. It may also modulate neurotransmitter release, potentially contributing to its efficacy in other conditions like epilepsy. It does not interact with dopamine receptors, and its antihistaminic properties are relatively weak.
Elimination Pathways: Flunarizine is extensively metabolized in the liver, with minimal renal excretion. The metabolites are primarily eliminated via biliary/fecal routes.
Dosage
Standard Dosage
Adults:
The initial dose is 10 mg daily taken at night for adults under 65 years old. For adults 65 years and older, the initial dose is 5 mg daily at night. If depressive symptoms, extrapyramidal symptoms, or other intolerable adverse effects occur, discontinue the medication. If no significant improvement is observed after 2-3 months, the patient may be considered a non-responder, and flunarizine should be discontinued.
For maintenance therapy, if the initial treatment is successful, the daily dose can be continued but interrupted by two consecutive drug-free days per week (e.g., Saturday and Sunday). Even if effective and well-tolerated, prophylactic treatment should be interrupted after 6 months. Re-initiate treatment if migraines return.
Children:
Flunarizine is not recommended for children under 18. Some guidelines suggest starting at 5 mg daily for children weighing over 40 kg. Pediatric use requires careful monitoring.
Special Cases:
- Elderly Patients: The initial dose is reduced to 5 mg daily due to increased sensitivity to side effects.
- Patients with Renal Impairment: No dose adjustments are provided in the manufacturer’s labeling. Drug accumulation is unlikely, as minimal renal excretion takes place. Use with caution.
- Patients with Hepatic Dysfunction: No dose adjustments are provided. Use cautiously as flunarizine is metabolized by the liver.
- Patients with Comorbid Conditions: Use with caution in patients with depression, Parkinson’s disease, or other extrapyramidal disorders.
Clinical Use Cases
Flunarizine is not indicated for use in acute medical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergencies like status epilepticus or cardiac arrest. Its use is limited to migraine prophylaxis and vestibular disorders. It is not recommended or effective for treating acute migraine attacks.
Dosage Adjustments
Dose adjustments may be necessary for elderly patients and those with hepatic impairment. Clinical monitoring for adverse events, especially CNS-related effects, is crucial for determining dose modifications.
Side Effects
Common Side Effects:
Increased appetite, weight gain, drowsiness, fatigue, nasal congestion, depression.
Rare but Serious Side Effects:
Extrapyramidal symptoms (e.g., tremors, rigidity, parkinsonism), severe depression.
Long-Term Effects:
Weight gain, potential for extrapyramidal symptoms with prolonged use.
Adverse Drug Reactions (ADR):
Extrapyramidal reactions, severe depression, allergic reactions.
Contraindications
- Hypersensitivity to flunarizine.
- History of depression or recurrent depression.
- Pre-existing Parkinson’s disease or other extrapyramidal disorders.
- Concurrent use of CNS depressants.
Drug Interactions
Flunarizine interacts with several medications, including:
- CNS depressants (e.g., alcohol, benzodiazepines, antihistamines): Increased sedation.
- Anticonvulsants (e.g., phenytoin, carbamazepine): Reduced flunarizine levels.
- Tricyclic antidepressants (e.g., amitriptyline): Increased risk of side effects.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C. As a precautionary measure, it is preferable to avoid the use of flunarizine during pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy. However, human studies lack data. Fetal risks are not well-established but are not known to cause teratogenicity. Flunarizine is not recommended during breastfeeding due to potential neonatal exposure.
Drug Profile Summary
- Mechanism of Action: Calcium channel blocker, stabilizes vascular smooth muscle.
- Side Effects: Weight gain, drowsiness, fatigue, depression, extrapyramidal symptoms.
- Contraindications: Depression, Parkinson’s disease, extrapyramidal disorders.
- Drug Interactions: CNS depressants, anticonvulsants.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 5-10 mg daily (initially 10 mg at night for those under 65); Elderly: Initially 5 mg daily at night.
- Monitoring Parameters: Weight, mood, extrapyramidal symptoms.
Popular Combinations
Flunarizine is typically used as monotherapy for migraine prophylaxis. Combining it with other prophylactic agents is not routinely recommended due to the increased risk of side effects and lack of strong evidence for synergistic efficacy. However, some studies have explored combinations with topiramate.
Precautions
- Pre-screening for depression, Parkinson’s disease, and extrapyramidal disorders.
- Monitor weight gain.
- Avoid alcohol and other CNS depressants.
- Caution in elderly patients and those with hepatic impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Flunarizine?
A: Adults under 65: Initially 10 mg daily at night. Elderly (65 and over): Initially 5 mg daily at night. Maintenance dose: May continue daily dose with two drug-free days per week.
Q2: What are the most common side effects?
A: Weight gain, drowsiness, fatigue, nasal congestion.
Q3: Can Flunarizine be used to treat an acute migraine attack?
A: No, it is not effective for treating acute migraines. It is used for migraine prevention.
Q4: Is Flunarizine safe during pregnancy?
A: It’s generally avoided during pregnancy due to limited human safety data. Discuss with your doctor.
Q5: What are the contraindications for Flunarizine?
A: Depression, Parkinson’s disease, extrapyramidal disorders, hypersensitivity to flunarizine.
Q6: How long does it take for Flunarizine to become effective?
A: It may take several weeks (2-3 months) to see the full prophylactic effect.
Q7: Can Flunarizine be used in children?
A: It is not recommended for children under 18. Pediatric use should be closely monitored by a doctor.
Q8: Does Flunarizine interact with other medications?
A: Yes, it can interact with CNS depressants and certain anticonvulsants.
Q9: What should patients do if they miss a dose?
A: Take the missed dose as soon as remembered, unless it’s close to the next scheduled dose. Do not double the dose.
Q10: What is the maximum duration of treatment for Flunarizine?
A: Prophylactic treatment is generally interrupted after 6 months, even if effective.
