Flunarizine (Sibelium) is a calcium channel blocker with cerebrovascular selectivity. It has an antihistamine (H1-blocking) and calmodulin-binding properties.
Flunarizine Uses:
-
Migraine:
- It is used in the prophylaxis of migraine with or without aura in patients who have frequent and severe attacks and do not tolerate or do not respond to other therapies (due to adverse effects).
-
Limitation of use:
- It is not indicated for the treatment of acute attacks of migraine.
Flunarizine dose in Adults
Flunarizine dose in the prophylaxis of Migraine:
-
Adults <65 years:
- 10 mg orally once a day.
- The treatment may be discontinued if no improvement is noted after 3 months of the treatment.
- Withholding the drug for two consecutive days in a week reduces the incidence of adverse events associated with the drug.
-
Off-label dosing:
- Adults: 5 to 10 mg orally once a day.
Flunarizine use in children:
Not indicated for use in children.
Pregnancy Risk Category: B
- Negative events have been documented in animal reproduction studies.
Use flunarizine while breastfeeding
- It is unknown if the drug will be excreted into breastmilk. It is recommended that breastfeeding mothers avoid its use.
Flunarizine Dose in Kidney Disease:
- The manufacturer has not recommended any adjustments in the dose.
- It has minimal urinary excretion, therefore, dose adjustment is less likely to be required.
Flunarizine Dose in Liver disease:
- The manufacturer has not recommended any adjustments in the dose.
- Since, it is metabolized in the liver, it should be used with caution in patients with liver disease.
Side effects of Flunarizine (Sibelium):
-
Central Nervous System:
- Drowsiness
- Anxiety
- Depression
- Dizziness
- Extrapyramidal Reaction
- Fatigue
- Insomnia
- Motor Dysfunction
- Sedation
- Sleep Disorder
- Vertigo
-
Dermatologic:
- Skin Rash
-
Endocrine & Metabolic:
- Weight Gain
- Galactorrhea
- Increased Serum Prolactin
- Menstrual Disease
-
Gastrointestinal:
- Heartburn
- Increased Appetite
- Nausea
- Stomach Pain
- Vomiting
- Xerostomia
-
Neuromuscular & Skeletal:
- Myalgia
- Weakness
Contraindications to Flunarizine (sibelium):
- Allergy reactions to any component of the drug or the drug itself
- Patients who have a history depressed
- Patients who have preexisting Parkinson disease symptoms or extrapyramidal disorders
Warnings and precautions
-
CNS effects
- It is possible to develop CNS depression after using it. This can lead to mental and physical impairments.
- People who perform tasks that require mental alertness, such as drivers or those who operate heavy machinery, may be advised to take the drug with caution.
- It has been reported that it can cause progressive fatigue. It is important to monitor patients for symptoms and severity. It is possible that treatment should be stopped.
-
Depression
- Young patients may experience depression or worsening symptoms.
- Patients who have had depression in the past should not use it.
- For the detection of depression symptoms in other patients, it is possible to monitor them at regular intervals.
-
Endocrine effects
- Galactorrhea may occur in female patients who have mild, but significant hyperprolactinemia or menstrual irregularities.
- Releasing treatment results in improvement.
-
Extrapyramidal symptoms
- Extrapyramidal symptoms can be observed that may need treatment interruption. The drug can be discontinued to reverse the symptoms.
- Elderly patients are at greater risk for extrapyramidal symptoms.
- Patients suffering from Parkinson's disease or extrapyramidal disorders should not use it.
-
Hepatic impairment
- Patients with liver disease should not use it as it undergoes hepatic metabolic.
Flunarizine: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Alcohol (Ethyl) |
CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). |
|
Alizapride |
May enhance the CNS depressant effect of CNS Depressants. |
|
Brexanolone |
CNS Depressants may enhance the CNS depressant effect of Brexanolone. |
|
Brimonidine (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Bromopride |
May enhance the CNS depressant effect of CNS Depressants. |
|
Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Cannabis |
May enhance the CNS depressant effect of CNS Depressants. |
|
CarBAMazepine |
May decrease the serum concentration of Flunarizine. |
|
Chlorphenesin Carbamate |
May enhance the adverse/toxic effect of CNS Depressants. |
|
CNS Depressants |
May enhance the adverse/toxic effect of other CNS Depressants. |
|
Dimethindene (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Doxylamine |
May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. |
|
Dronabinol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Esketamine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Fosphenytoin |
May decrease the serum concentration of Flunarizine. |
|
HydrOXYzine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Kava Kava |
May enhance the adverse/toxic effect of CNS Depressants. |
|
Lofexidine |
May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Magnesium Sulfate |
May enhance the CNS depressant effect of CNS Depressants. |
|
MetyroSINE |
CNS Depressants may enhance the sedative effect of MetyroSINE. |
|
Minocycline |
May enhance the CNS depressant effect of CNS Depressants. |
|
Mirtazapine |
CNS Depressants may enhance the CNS depressant effect of Mirtazapine. |
|
Nabilone |
May enhance the CNS depressant effect of CNS Depressants. |
|
Phenytoin |
May decrease the serum concentration of Flunarizine. |
|
Piribedil |
CNS Depressants may enhance the CNS depressant effect of Piribedil. |
|
Pramipexole |
CNS Depressants may enhance the sedative effect of Pramipexole. |
|
ROPINIRole |
CNS Depressants may enhance the sedative effect of ROPINIRole. |
|
Rotigotine |
CNS Depressants may enhance the sedative effect of Rotigotine. |
|
Rufinamide |
May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. |
|
Selective Serotonin Reuptake Inhibitors |
CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. |
|
Tetrahydrocannabinol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tetrahydrocannabinol and Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Trimeprazine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Risk Factor D (Consider therapy modification) |
|
|
Blonanserin |
CNS Depressants may enhance the CNS depressant effect of Blonanserin. |
|
Buprenorphine |
CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. |
|
Chlormethiazole |
May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. |
|
Droperidol |
May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Flunitrazepam |
CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. |
|
HYDROcodone |
CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Methotrimeprazine |
CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. |
|
Opioid Agonists |
CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
OxyCODONE |
CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Perampanel |
May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. |
|
Sodium Oxybate |
May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. |
|
Suvorexant |
CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. |
|
Tapentadol |
May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Zolpidem |
CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. |
|
Risk Factor X (Avoid combination) |
|
|
Azelastine (Nasal) |
CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). |
|
Bromperidol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Orphenadrine |
CNS Depressants may enhance the CNS depressant effect of Orphenadrine. |
|
Oxomemazine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Paraldehyde |
CNS Depressants may enhance the CNS depressant effect of Paraldehyde. |
|
Thalidomide |
CNS Depressants may enhance the CNS depressant effect of Thalidomide. |
Monitoring parameters:
Monitor the patients for
- extrapyramidal effects,
- Depression
- Fatigue and somnolence
How to administer Flunarizine (Sibelium)?
It should be administered at bedtime with a glass of water.
Mechanism of action of Flunarizine (Sibelium):
- Flunarizine, a selective calcium channel blocking agent, prevents calcium from entering cells by inhibiting transmembrane calcium flow.
- It is antihistamine (H-1-blocking) and has other properties. It reduces migraine attacks, both acute and long-term.
Absorption:
- Well absorbed
Protein binding:
- 90%
Metabolism:
- Hepatic: N-oxidation, aromatic hydroxylation
Half-life:
- Variable; Alpha: about 2.4 to 5.5 hours (single dose);
- Beta: about 4 days (single dose),
- About 19 days (multidose)
Time to peak Plasma concentrations:
- 2 to 4 hours
Excretion:
- Feces (<6% at 48 hours);
- urine (minimal)
International Brands of Flunarizine:
- NOVO-Flunarizine
- Axilin
- Bartolium
- Bedriol
- Buflin
- Cebrium
- Cevadil
- Cymalium
- Dinegal
- Dizine
- Fasolan
- Flarin
- Flaryzil
- Flucilium
- Fludan
- Fludil
- Flumig
- Flunarin
- Flunariz
- Flunatop
- Flunavert
- Fluver
- Fluzina
- Forknow
- Frego
- Galium
- Gradient
- Headache
- Irrigor
- Liberal
- Lunar
- MGR
- Migon
- Natil-N
- Norium
- Poli-Flunarin
- Seremig
- Sibelium
- Silium
- Sinral
- Suzin
- Vanid
- Vertig
- Vertimigr
- Veseda
- Xepalium
- Zinasen
Flunarizine Brand Names in Pakistan:
Flunarizine 5 mg capsules |
|
| Flunzic | Panacea Pharmaceuticals |
| Migram | Amarant Pharmaceuticals (Pvt) |
| Polyzine | Polyfine Chempharma (Pvt) Ltd. |
| Sibelium | Janssen-Cilag |
Flunarizine 10 mg Capsules |
|
| Migram | Amarant Pharmaceuticals (Pvt) |
