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 : , 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 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. Thomas Headache 31: , 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 al Cephalalgia 2002;22: 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 effects 5mg:16.7%. 10mg: 19.3%. Propranolol:16.7%

HC Deiner et al J Neurol 2004;251: patients Topiramate 100mg v Topiramate 200mg v Propranolol 160mg v Placebo Responders: Placebo 23% TPM 100mg 37% TPM 200mg 35% Propranolol 43%

Sorensen PS Headache 31: 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?