Flunarizine Hydrochloride

1. Health Canada Product Monograph — Flunarizine Hydrochloride

• Used for the prevention of migraine, with or without aura, in patients with frequent and severe attacks who have not responded well to other treatments or who cannot tolerate them due to side effects.
• Not indicated for treating an acute migraine attack once it has already started.

• There is no data supporting use during pregnancy, so it should not be given to pregnant women unless the anticipated benefit outweighs the potential risk.

• Should not be used while breastfeeding, as animal studies show it passes into milk at concentrations well above those in plasma, and no human breast milk data are available.

• Safety and effectiveness for migraine prevention have not been established in patients over 65, and this age group appears to be at particular risk of movement disorders (extrapyramidal symptoms) with flunarizine treatment.

• Not authorized for use in patients under 18 years of age, as safety and effectiveness have not been established in this population.

• The recommended dose for adults under 65 is 10 mg taken once daily at night.
• If depressive, movement-related (extrapyramidal), or other unacceptable side effects occur, treatment should be stopped.
• If no meaningful improvement is seen after 3 months, the patient should be considered a non-responder and the medication discontinued.
• For treatment extending beyond 6 months, patients should continue to be monitored closely for side effects, particularly nervous system effects, with prompt discontinuation at the first sign of a problem.
• If a dose is missed, take it as soon as remembered; if it is almost time for the next dose, skip the missed one and resume the regular schedule rather than doubling up.

• Drowsiness or sedation is common and may be accompanied by a general sense of fatigue.
• Weight gain and increased appetite may occur.
• Anxiety may occur.
• Dizziness or a spinning sensation (vertigo) may occur.
• Insomnia or other sleep changes may occur.
• Nausea, heartburn, or stomach discomfort may occur.
• Dry mouth may occur.
• Muscle aches may occur.
• Skin rash may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Flunarizine can cause or worsen depression, which is the most serious effect seen in clinical use and has led to treatment discontinuation; this appears more common in younger patients and those with a personal or family history of depression.
• Movement disorders resembling Parkinson's disease, including tremor and slowed movements, can develop even at recommended doses and are more likely in older adults; these symptoms are generally reversible after stopping the drug but do not respond to standard anti-Parkinson's medication.
• Fatigue can progressively worsen during treatment and may require stopping the medication.
• Unexpected breast milk production (galactorrhea) has been reported in some female patients, sometimes accompanied by menstrual irregularities.
• Contact your prescriber promptly, or seek immediate medical attention, for new or worsening depression, tremor, muscle stiffness, uncontrolled movements, or significant ongoing fatigue.

• Flunarizine should not be used at all, rather than merely with caution, in patients with a history of depressive illness or pre-existing symptoms of Parkinson's disease or other movement disorders, as these are formal contraindications.
• Use with caution in patients with liver impairment, as the drug is metabolized by the liver.
• Patients should be monitored regularly for movement disorders, depressive symptoms, and fatigue throughout treatment.
• Caution is needed with driving or operating machinery, since sedation and drowsiness can occur.
• Alcohol, sleeping pills, and anti-anxiety medications should be avoided or used cautiously, as they can worsen sedation.

• Known hypersensitivity to flunarizine or to any ingredient in the formulation.
• Current or past history of depressive illness.
• Pre-existing symptoms of Parkinson's disease or other movement (extrapyramidal) disorders.

• Anticonvulsants such as phenytoin, carbamazepine, valproic acid, and mephenytoin can lower flunarizine blood levels through enhanced liver metabolism, and combining two or more anticonvulsants further reduces flunarizine levels, so monitoring of its effect is recommended.
• Alcohol, hypnotics, or tranquilizers taken together with flunarizine can cause excessive sedation and should be avoided.
• Other antihypertensive medications may have an additive blood-pressure-lowering effect when combined with flunarizine, and a dose reduction of the antihypertensive may be needed.
• No clinically significant interaction has been shown with warfarin, glibenclamide, or insulin, but caution and monitoring are still reasonable when starting or stopping flunarizine in patients taking these medications.

• No specific food interactions have been established for flunarizine.

• Taken once daily at night.

• Store at room temperature (15-30 degrees C) and protect from light and moisture.

• Flunarizine is used to help prevent migraine attacks in people with frequent, severe migraines who have not done well on other treatments; it does not treat a migraine once it has started.
• Take one capsule once daily at night, and do not double up if you miss a dose - just take it when you remember or skip it if it is almost time for the next one.
• Common effects include drowsiness, weight gain, dizziness, and anxiety.
• Contact your doctor or pharmacist promptly if you notice new or worsening low mood, tremor, stiffness, or unusual movements, or if fatigue becomes significant, as these need medical evaluation.
• Avoid alcohol and be cautious with driving or operating machinery until you know how this medication affects you.
• Store at room temperature away from light and moisture, and do not use if you are pregnant, breastfeeding, or have a history of depression or Parkinson's disease without discussing this with your doctor.