FLUNARIZINE

2 Recommended Dose and Dosage Adjustment  Adults The recommended dose is 10 mg daily (at night) for patients younger than 65 years of age. If, during this treatment, depressive, extrapyramidal or other unacceptable adverse experiences occur, administration should be discontinued.

If, after 3 months of this initial treatment, no significant improvement is observed, the patient should be considered a non-responder and administration should also be discontinued. If treatment goes beyond 6 months, patients should continue to be closely monitored for side effects, in particular CNS related events and therapy should be discontinued at the first sign of adverse reactions.

See 7 WARNINGS AND PRECAUTIONS, Extrapyramidal Symptoms. FLUNARIZINE (flunarizine hydrochloride) Page 5 of 23 Although there are no long-term controlled clinical trials with FLUNARIZINE, clinical experience suggests that two successive drug-free days per week may decrease the potential for adverse reactions.

However, it should be noted that a brief interruption in therapy will not significantly reduce the exposure to FLUNARIZINE, given its long half-life (19 days).  Pediatrics Health Canada has not authorized an indication for pediatric use.

5 Missed Dose If the patient misses a dose, instruct the patient to take the dose as soon as they remember. If it is almost time for the next dose, inform the patient to skip the missed dose and continue the regular dosing schedule.

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. In clinical trials with FLUNARIZINE in migraine patients, drowsiness (also described as sedation or fatigue) as well as weight gain (and/or increased appetite) occurred fairly frequently, in the order of 20 and 15%, respectively.

1%) required withdrawal from FLUNARIZINE therapy due to drowsiness and weight gain, respectively. The most serious side effect encountered in migraineurs during clinical trials was depression. 3%) were withdrawn due to depression. Clinical experience in other indications and epidemiologic surveys suggest that extrapyramidal symptoms may develop during FLUNARIZINE therapy.

Elderly patients are particularly at risk. See 2 CONTRAINDICATIONS and 7 WARNINGS AND PRECAUTIONS, Extrapyramidal Symptoms. Other side effects encountered in clinical trials for migraine prophylaxis included the following: FLUNARIZINE (flunarizine hydrochloride) Page 8 of 23 Central Nervous System Disorders: Anxiety, dizziness/vertigo insomnia and sleep change; Gastrointestinal Disorders: Emesis, gastralgia, heartburn, nausea; Miscellaneous: Asthenia, dry mouth, muscle aches, skin rash.

5 Post-Market Adverse Reactions International post-marketing experience suggests that patients between 20 and 54 years of age with a personal or familial history of depression are particularly at risk. See 2 CONTRAINDICATIONS and 7 WARNINGS AND PRECAUTIONS, Depression.

2 Recommended Dose and Dosage Adjustment  Adults The recommended dose is 10 mg daily (at night) for patients younger than 65 years of age. If, during this treatment, depressive, extrapyramidal or other unacceptable adverse experiences occur, administration should be discontinued.

If, after 3 months of this initial treatment, no significant improvement is observed, the patient should be considered a non-responder and administration should also be discontinued. If treatment goes beyond 6 months, patients should continue to be closely monitored for side effects, in particular CNS related events and therapy should be discontinued at the first sign of adverse reactions.

See 7 WARNINGS AND PRECAUTIONS, Extrapyramidal Symptoms. FLUNARIZINE (flunarizine hydrochloride) Page 5 of 23 Although there are no long-term controlled clinical trials with FLUNARIZINE, clinical experience suggests that two successive drug-free days per week may decrease the potential for adverse reactions.

However, it should be noted that a brief interruption in therapy will not significantly reduce the exposure to FLUNARIZINE, given its long half-life (19 days).  Pediatrics Health Canada has not authorized an indication for pediatric use.

5 Missed Dose If the patient misses a dose, instruct the patient to take the dose as soon as they remember. If it is almost time for the next dose, inform the patient to skip the missed dose and continue the regular dosing schedule.

5 OVERDOSAGE Symptoms On the basis of the pharmacological properties of the drug, sedation and asthenia may be expected to occur. g. g. tachycardia). Treatment There is no specific antidote. Activated charcoal may be given if considered appropriate.

For management of a suspected drug overdose, contact your regional poison control centre. 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 1 – Dosage Forms, Strengths, Composition and Packaging Each grey opaque body, red opaque cap, hard gelatin capsule, imprinted "5", with a white powder fill, contains flunarizine hydrochloride equivalent to 5 mg flunarizine.

FLUNARIZINE is contraindicated in:  Patients with known hypersensitivity to the drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

 Patients with a history of depressive illness, or with pre-existing symptoms of Parkinson's disease or other extrapyramidal disorders. 5 Post Market Adverse Reactions)