Flunarazine

about flunarizine drug

1. Flunarizine Diphenylpiperazine

2. BRAND NAME Fluvert Migarid 10mg Sibelium 10mg Flunarsac 10mg Grenil F 10mg Fludrin 10mg

3. INDICATION The medication is a calcium channel blocker prescribed for Migraine occlusive peripheral vascular disease Vertigo of central and pheripheral origin

4. DOSE AND DOSAGE It comes as a tablet to take by mouth, with or without food. DOSAGE AND DIRECTIONS FOR USE Migraine Prophylaxis Starting Dose: Two 5 mg capsules (10 mg) SIBELIUM at night in patients less than 65 years of age and 5 mg daily in patients older than 65 years . If, during this treatment depressive, extrapyramidal or other unacceptable symptoms occur, administration should be discontinued. If, after 2 months of this initial treatment, no significant improvement is observed, the patient should be considered a non-responder and administration should be discontinued.

5. Maintenance Treatment: If a patient is responding satisfactorily and if a maintenance treatment is needed, the dose should be decreased to 5 days treatment at the same daily dose with two successive medicine free days every week. Even if the prophylactic maintenance treatment is successful and well tolerated, it should be interrupted after 6 months and it should be re-initiated only if the patient relapses. Vertigo The same dosage should be used as for migraine, but the starting treatment should not be given longer than needed for symptom control, which generally takes less than two months . After one month of treatment for chronic vertigo or after two months treatment for paroxysmal vertigo, no significant improvement is observed, the patient should be considered a non-responder and administration should be discontinue

6. CONTRA INDICATION Parkinson’s disease History of Extra pyramidal disorders History of depression Breast feeding (Pregnancy).

7. Pregnancy Category : Category C : Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

8. Extra pyramidal disorder : Extra pyramidal motor signs have been reported in 12 patients given flunarizine 10-40mg daily for between 3 weeks and 15 months - 11 had depression Partial and complete improvement of symptoms occurred after withdrawal of flunarizine

9. Side effects Most Common - Drowsiness 20 %,weight gain 15% and depression.  Gastrointestinal - Heartburn, nausea, vomiting and stomach pain.   Central Nervous system  - dizziness , and anxiety disorder .   Miscellaneous - Dry mouth, weakness, muscle aches and skin rash.

10. PHARMACOKINETICS PROFILE Absorption -   Flunarizine is well absorbed(>80%) from the gut, reaching peak plasma levels within 2 - 4 hours ( 50-100 micro gram ) and reaching steady state at 5 - 6 weeks . Distribution - Highly lipophilic . Protein-binding: >90%. It has a larger volume of distribution of approximately 78L/ kgin healthly subjects .

11. Approximately 207L/kg in epileptic patients indicating extensive distribution to the extravascular tissue. The drug quickly crosses the blood brain barrier; concentrations in the brain are approximately 10 times higher than those in plasma. Metabolism – Flunarizine is metabolised in the liver into at least 15 metabolites. The primary metabolic pathway is CYP2D6 Half life – 18 days .

12. 00000 Excretion:   Flunarizine is primarily eliminated as parent drug and metabolites through the faeces via bile. Within 24 to 48 hours after administration, approximately 3% to 5% of the administered dose of flunarizine is eliminated in the faeces as parent drug and metabolites and <1% is excreted as unchanged drug in urine. 

13. INTERACTION Hepatic enzyme inducers such as carbamazepine,phenytoin,valporate may interact by increasing its metabolism. Excessive sedation can occur when alcohol, hypnotics are taken simultaneously with flunarizine

14. MECHANISM OF ACTION Mechanism of action for migraine prophylaxis is unclear Flunarizine is a relatively weak Calcium channel blocker that also inhibit sodium channels. It is claimed to be cerebro -selective calcium channel blocker:may benefit migraine by reducing intracellular calcium overload by reducing excessive transmembrane calcium influxes due to brain hypoxia and other cause .

15. Special precaution Caution should be exercised in patients with history of heart, liver, kidney diseases, glucoma , elderly, children, during pregnancy and breastfeeding.

16. A small number of comparative studies have shown flunarazine to be effective as PIZOTIFEN in migraine prophylaxis ,in longer term studies as effective as cinnarizine in vertigo of central origin .

17. Do not stop taking the medication due to lack of effect within the first six to eight weeks. it is probable that the considerable inter-individual variability that occurs in the plasma concentrations of flunarizine at the steady state is a consequence of the extensive pre-systemic metabolism that the drug undergoes.

18. Causes of Migraine Migraine is a complex disorder involving the brain and the blood vessels around the brain and head.  The brain may become hyperactive in response to certain environmental triggers, such as light or smells, for reasons that are not known. This starts a series of chemical changes that irritate the pain sensing nerves around the head and cause blood vessels to expand and leak chemicals which further irritate the nerves.