Transcript MISOPROSTOL: a drug that´s too hot to handle?

Off-label use of
MISOPROSTOL
Dr Andrew Weeks
Clinical Lecturer
“Misoprostol seems excellent for use in
obstetrics and gynaecology”
“But its not licensed, and the drug
company haven’t approved it. You
will be in trouble if you use it”
Outline
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History of misoprostol
Drug company attitudes
Licensing laws
The way forward
History of Misoprostol
1985
1985
2000
2003
Misoprostol licensed by Searle
Searle & Monsanto merger
Monsanto & Pharmacia merger
= Pharmacia
Pharmacia and Pfizer merger
= Pfizer
Misoprostol
1984 first licensed
1987 first use for abortion
(1989 illegal use in brazil common)
1992 first use for IOL and miscarriage
1996 first use for PPH prevention
2000 FDA license for abortion (with
mifepristone for medical abortion)
But - no license applied for
• Searle decision not to apply for it
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Lucrative gastric ulcer market
Costs in price and reputation
US publicity on ‘abortion drug’
Experience of Roussel with mifepristone
• 1997 gave miso to WHO for PPH trial
• Public letter in 2000
What is a license?
• Protect patients from drug companies
• NOT to guide doctors
• Costs $900 million to get a license
National drug authorities (MHRA / FDA)
- risk benefit analysis
Drug company - cost-benefit analysis
Licensing of drugs
• Usually new expensive drugs in low risk
indications
NOT FOR
• Old drugs in new indications
• Cheap / generic drugs
• High risk situations (paeds / O&G)
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Nitrofurantoin for UTI in pregnancy
Nevirapine for reduction of mother-tochild HIV transmission
Nifedipine for high bp in pregnancy
Oxytocin 10iu im to prevent PPH
Betamethasone for lung maturation
46% off-label use in European paediatric wards
Conroy et al BMJ 2000;320:79-82.
Misoprostol use for
Reproductive Health
"Yes "
– FDA
– RCOG / ACOG
– Specialist societies
– British National Formulary
" No "
– Drug company
Who do you trust?
Drug and indication
1. Oxytocin 10 im to prevent PPH
2. Misoprostol for social induction or pregnancy
before 24 weeks
3. Antenatal betamethasone to prevent neonatal
respiratory distress syndrome in premature
deliveries
4. Clindamycin to treat  haemolytic streptococci
in pregnancy
5. Oxytocin 5iv to treat missed miscarriage
6. Norethisterone (day 19-26) to treat
menorrhagia
Licensed?
BNF
RCOG
X
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X
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X
X
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X
X
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X
X
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X
Legal Test in UK
Bolam test
‘what a representative group of doctors at the
same level would reasonably be expected to do’
1. Government guidelines committee (NICE)
2. WHO / National O&G Society guidelines
3. Local guidelines
4. BNF
5. License
The Way Forward
• Produce evidence-based guidelines at
national / international level
• Ignore drug license for now if better
evidence available
(consider joint licensing / guideline groups)
• RH organisations should produce
statements to support local doctors
www.misoprostol.org