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Dear Readers! I started this blog when my daughter was in the NICU. She had ventriculitis. Her CSF report grew E.coli. But, she was injected Teicoplanin directly into her brain. The doctors made two errors here:

Teicoplanin is for gram-positive bacteria only. It does not treat E.coli.
Teicoplanin is not for intraventricular use. The manufacturer strongly discourage injecting Teicoplanin into the brain.

My daughter bled into the brain. She lived for another two years and ultimately died.

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Flunarizine (Sibelium) - Uses, Dose, Side effects, Brands

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:

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)

Flunarizine (Sibelium) - Uses, Dose, Side effects, Brands

Flunarizine Uses:

Migraine:

Flunarizine dose in Adults

Flunarizine dose in the prophylaxis of Migraine:

Adults <65 years:

Off-label dosing:

Flunarizine use in children:

Pregnancy Risk Category: B

Use flunarizine while breastfeeding

Flunarizine Dose in Kidney Disease:

Flunarizine Dose in Liver disease:

Side effects of Flunarizine (Sibelium):

Central Nervous System:

Dermatologic:

Endocrine & Metabolic:

Gastrointestinal:

Neuromuscular & Skeletal:

Contraindications to Flunarizine (sibelium):

Warnings and precautions

CNS effects

Depression

Endocrine effects

Extrapyramidal symptoms

Hepatic impairment

Monitoring parameters:

How to administer Flunarizine (Sibelium)?

Mechanism of action of Flunarizine (Sibelium):

International Brands of Flunarizine:

Flunarizine Brand Names in Pakistan:

Flunarizine 5 mg capsules

Flunarizine 10 mg Capsules

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