1. Flunarizine for migraine
prophylaxis
Steven Elliot GPwSI NHS Salford

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

3. 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

4. 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

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

6. Contra-indications
• Parkinson’s disease
• History of EP syndromes
• History of depression
• Breast feeding
• (Pregnancy)
Caution
• Elderly
• Hepatic disease

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

8. Interactions
• Alcohol
• Hypnotics /tranquilizers
• COC
• Anticholinergics
• Anticonvulsants

9. 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

10. 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

11. 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

12. 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)

13. M. Thomas
Headache 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

14. HC Deiner et al
Cephalalgia 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 effects
5mg:16.7%. 10mg: 19.3%. Propranolol:16.7%

15. HC Deiner et al
J 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%

16. Sorensen PS
Headache 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

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

18. 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

19. 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

21. 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?