Flunarizine for migraine prophylaxis

Steven Elliot GPwSI NHS Salford

Content

• Pharmacology• Indications for use• Contra-indications• Adverse effects• Evidence base• Prescribing issues

Pharmacokinetics

• Readily absorbed• Steady state after 5-6 weeks• Wide distribution• Lipophyllic • Binds strongly to protein• Dissolves poorly in water• Crosses blood brain barrier• Metabolised in liver with first pass effect• Half life 7-10days

Mechanism of action

• Non selective Calcium antagonist• Anti dopaminergic• H1 antihistamine• (Stabilizers vasomoticity)• Raises excitatory threshold in CSD• Protects against hypoxia• Reduces epileptic neuronal activity• Effect on Calmodulin

Indications

• Prophylaxis of migraine• Symptomatic treatment of dizziness• (Peripheral vascular disease)• (Alternating hemiplegia)• (Epilepsy adjuvant)

Contra-indications

• Parkinson’s disease• History of EP syndromes• History of depression• Breast feeding• (Pregnancy)Caution• Elderly• Hepatic disease

Adverse effects

• Weight gain• Sedation• Depression• EP syndrome (de Melo-Souza syndrome)• Headache/insomnia/asthenia/GI

Interactions

• Alcohol• Hypnotics /tranquilizers• COC• Anticholinergics• Anticonvulsants

P. Louis, Headache 1980 21:235-239,

• Belgium general practice• 3month double blind no crossover• 10mg v placebo• 58 patients• 57% v 14% reduction migraine attacks • (3.5 to 2 cf 3.5 to 3 in placebo)• More marked in month 3

C. Frenken Clin Neurol Neurosurg 1984 Vol 86 Pt 1 17-20

• Netherlands primary care• 35 patients• 12 weeks • 10mg v placebo• 75% reduction in active v 31% placebo

G. Mendenopoulous Cephalalgia 1985 ;5:31-7

• Greek secondary care• 20 patients• Placebo v 10mg 3-4 months• 50% reduction v 30% increase in placebo

PS Sorenson Cephalalgia 1986 ;6:7-14.

• Danish secondary care• 29 patients• Double blind crossover trial• 16 weeks treatment period• 10mg v placebo• 50% reduction in migraine frequency in last 4

weeks (15% placebo)

M. ThomasHeadache 31:613-615, 1991

• India• 29 patients (14 dropped out)• 6months double blind crossover• 10mg v placebo• No decrease in migraine frequency• Reduced duration and severity

HC Deiner et alCephalalgia 2002;22:209-221

• 808 patients• Double blind 16 week treatment phase• 10mg(5days/week) v 5mg v Propranolol

160mg• Responders (50% reduction) 5mg:46%. 10mg:53%. Propranolol:48%• Drop out due to adverse effects5mg:16.7%. 10mg: 19.3%. Propranolol:16.7%

HC Deiner et alJ Neurol 2004;251:943-950

• 176 patients• Topiramate 100mg v Topiramate 200mg v

Propranolol 160mg v Placebo• Responders:Placebo 23%TPM 100mg 37%TPM 200mg 35%Propranolol 43%

Sorensen PSHeadache 31:650-655 1991

• 149 patients• Double blind 10mg v Metoprolol 200mg• 16weeks treatment phase• Both 37% reduction migraine days /month• 8% depression cf 3% with Metoprolol

Legal

• Not licensed for use in UK• Named patient basis• Best option for patient• Clinician/pharmacist take responsibility• Complex procedure

Pharmacist’s duties

• Make clinician aware unlicensed• Use licensed preparation first• Demonstrate best interest of patient• Benefits outweigh risks• Informed consent• Keep records for 5 years• PILS

Experience of use

Dr Nick Silver , Walton Centre• Written and verbal advise• Stop if drowsy• Watch for mood change• Does not use with beta-blockers• Uses 5-15mg• Reserves for refractory patients/prolonged

aura/hemiplegic aura/severe migrainous vertigo

Questions

• Should we offer it at all?• If use which patient groups?• Is there a specific role in hemiplegic migraine

or migraine with prolonged aura?• Should BASH develop a guideline?