Sibelium, with the active ingredient flunarizine dihydrochloride, is a selective calcium channel blocker specifically indicated for the prophylaxis of migraine. It represents a cornerstone in preventive neurological therapy, designed to reduce the frequency and severity of migraine attacks by modulating vascular and neuronal calcium influx. This expert-focused product card provides a comprehensive overview of its pharmacological profile, clinical application, and essential safety information for healthcare professionals managing patients with debilitating migraine disorders.

Features

• Active Ingredient: Flunarizine dihydrochloride 10mg
• Pharmacological Class: Selective calcium entry blocker with calmodulin binding properties
• Formulation: Film-coated tablet for oral administration
• Mechanism of Action: Inhibits calcium influx into vascular smooth muscle and neurons; also exhibits dopaminergic D2 receptor antagonist and histamine H1 antagonist activity
• Bioavailability: Nearly complete following oral administration, with peak plasma concentrations reached within 2-4 hours
• Half-life: Approximately 18 days, allowing for once-daily dosing and stable plasma levels
• Metabolism: Extensively hepatic, primarily via CYP2D6

Benefits

• Significantly reduces the frequency of migraine attacks, helping patients regain control over their daily lives.
• Decreases the intensity and duration of migraine episodes when they do occur, minimizing functional impairment.
• Offers a favorable pharmacokinetic profile with a long half-life, ensuring consistent 24-hour coverage from a single daily dose.
• Provides a well-tolerated prophylactic option with a established efficacy and safety profile based on decades of clinical use.
• Can lead to a reduced reliance on acute migraine medications (triptans, NSAIDs), potentially mitigating medication-overuse headache.
• Improves overall quality of life by reducing the burden of a chronic neurological condition.

Common use

Sibelium (flunarizine) is primarily prescribed for the prophylactic management of migraine headache. It is indicated for patients who experience frequent or severe migraine attacks that significantly impact their quality of life, typically defined as four or more migraine days per month. Its use is considered when non-pharmacological measures and other first-line prophylactic agents are ineffective, contraindicated, or not tolerated. It is not intended for the acute treatment of a migraine attack already in progress.

Dosage and direction

The recommended adult dosage for migraine prophylaxis is 10 mg (one tablet) once daily, taken in the evening with a meal to minimize potential drowsiness.

• Initiation: Treatment is usually initiated at 10 mg daily.
• Maintenance: After one month, if a satisfactory response is achieved and the drug is well-tolerated, the dose may be continued. In patients who respond but experience troublesome side effects (e.g., weight gain, drowsiness), a maintenance dose of 5 mg (half a tablet) every other day may be considered, though this is off-label and requires careful clinical judgement.
• Elderly: A starting dose of 5 mg daily is recommended due to potentially increased sensitivity.
• Duration: Treatment should be reassessed after 6 months of successful prophylaxis. A drug-free interval may be attempted to evaluate the continued need for therapy.
• The tablets should be swallowed whole with a glass of water and not chewed or crushed.

Precautions

• Extrapyramidal Symptoms: Flunarizine has dopamine antagonist properties. Use with extreme caution in patients with a history of extrapyramidal symptoms (e.g., parkinsonism, tremor, akathisia) or depression, as it may precipitate or exacerbate these conditions.
• Sedation: Sibelium can cause drowsiness and somnolence, especially at the beginning of therapy. Patients should be cautioned against driving or operating machinery until their individual response is known.
• Weight Gain: Significant weight gain is a commonly reported side effect. Patients should be advised to monitor their weight and maintain a healthy diet and exercise regimen.
• Hepatic Impairment: As flunarizine is extensively metabolized in the liver, it should be used with caution in patients with hepatic impairment. Consideration of a lower dose may be necessary.
• Renal Impairment: Caution is advised in patients with severe renal impairment, although dosage adjustment is not usually required.
• Pregnancy and Lactation: The use of Sibelium during pregnancy is not recommended unless the potential benefit justifies the potential risk to the fetus. It is excreted in breast milk; a decision should be made whether to discontinue nursing or discontinue the drug.

Contraindications

Sibelium is contraindicated in patients with:

• Known hypersensitivity to flunarizine, other piperazine derivatives, or any of the excipients in the formulation.
• History of depressive illness, or current symptoms of depression.
• Pre-existing extrapyramidal disorders, such as Parkinson’s disease.
• Severe hepatic impairment (Child-Pugh class C).

Possible side effect

The following adverse reactions have been reported, listed by system organ class and frequency (Very common: ≥1/10; Common: ≥1/100 to <1/10; Uncommon: ≥1/1,000 to <1/100).

• Nervous System Disorders: Very common: drowsiness, sedation. Common: headache, insomnia, dizziness, akathisia, depression. Uncommon: extrapyramidal symptoms (e.g., parkinsonism, tremor), exacerbation of pre-existing epilepsy.
• Gastrointestinal Disorders: Common: nausea, dry mouth, abdominal pain, increased appetite.
• General Disorders: Very common: weight gain. Common: fatigue, asthenia.
• Psychiatric Disorders: Common: depressive mood.
• Skin and Subcutaneous Tissue Disorders: Common: rash.

Drug interaction

• CNS Depressants: (e.g., alcohol, benzodiazepines, opioids, sedating antihistamines, other antipsychotics). Concomitant use may potentiate sedative effects. Enhanced caution is advised.
• Antihypertensives: Flunarizine may have additive hypotensive effects when combined with other blood pressure-lowering medications.
• Dopamine Agonists: (e.g., levodopa, bromocriptine). Flunarizine’s dopamine antagonist effect may reduce the efficacy of dopamine agonists used in Parkinson’s disease.
• CYP2D6 Inhibitors: (e.g., paroxetine, fluoxetine, quinidine). May increase plasma concentrations of flunarizine, potentially increasing the risk of adverse effects. Monitor patients closely.
• Hepatotoxic Drugs: Concurrent use with other drugs known to cause hepatotoxicity may increase the risk of liver injury.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. If it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not take a double dose to make up for the forgotten one. Maintaining the regular dosing schedule is more important than catching up on a single missed dose due to the drug’s long half-life.

Overdose

• Symptoms: Overdose would be expected to produce exaggerated pharmacological effects, primarily severe CNS depression (profound drowsiness, coma), hypotension, and bradycardia. Extrapyramidal symptoms and cardiac arrhythmias may also occur.
• Management: There is no specific antidote. Treatment is supportive and symptomatic. Gastric lavage may be considered if presented early. Vital signs, including ECG, should be monitored continuously. Management of hypotension and bradycardia may require appropriate supportive measures. Due to the long half-life, monitoring and supportive care may be required for an extended period.

Storage

• Store below 30°C (86°F).
• Keep the blister strips in the outer carton to protect from light and moisture.
• Keep out of the sight and reach of children.
• Do not use after the expiration date printed on the packaging.

Disclaimer

This information is intended for healthcare professionals and is a summary of the product characteristics. It is not exhaustive. The prescriber should refer to the full local prescribing information for complete details on contraindications, warnings, precautions, and adverse reactions before initiating treatment. The ultimate responsibility for patient care lies with the healthcare professional based on their clinical judgement and knowledge of the patient.

Reviews

• “A mainstay in my neurology practice for refractory migraine. The long half-life is a significant advantage for adherence. Monitoring for weight gain and mood changes is paramount, but in the right patient, the reduction in attack frequency is profound.” – Consultant Neurologist, 15 years experience.
• “Effective for many of my patients who have failed first-line options like beta-blockers or topiramate. The sedative effect, while common initially, often diminishes over time. Requires careful patient selection and ongoing dialogue about side effects.” – General Practitioner with a special interest in headache.
• “From a pharmacological perspective, its multi-modal mechanism provides a unique approach to prophylaxis. Its use has declined somewhat with newer agents, but it remains a valuable and cost-effective tool in the therapeutic arsenal.” – Clinical Pharmacologist.