Transcript Flunarizine for migraine prophylaxis

Flunarizine for migraine
prophylaxis
Steven Elliot GPwSI NHS Salford
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Pharmacology
Indications for use
Contra-indications
Adverse effects
Evidence base
Prescribing issues
Pharmacokinetics
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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
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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
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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
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Weight gain
Sedation
Depression
EP syndrome (de Melo-Souza syndrome)
Headache/insomnia/asthenia/GI
Interactions
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Alcohol
Hypnotics /tranquilizers
COC
Anticholinergics
Anticonvulsants
P. Louis,
Headache 1980 21:235-239,
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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
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Netherlands primary care
35 patients
12 weeks
10mg v placebo
75% reduction in active v 31% placebo
G. Mendenopoulous
Cephalalgia 1985 ;5:31-7
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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.
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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 31:613-615, 1991
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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;22:209-221
• 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%
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%
Sorensen PS
Headache 31:650-655 1991
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149 patients
Double blind 10mg v Metoprolol 200mg
16weeks treatment phase
Both 37% reduction migraine days /month
8% depression cf 3% with Metoprolol
Legal
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Not licensed for use in UK
Named patient basis
Best option for patient
Clinician/pharmacist take responsibility
Complex procedure
Pharmacist’s duties
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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
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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?