Misoprostol use in Obstetrics and Gynaecology

Post graduate presentation

1. MISOPROSTOL USE IN OBSTETRICS
AND GYNAECOLOGY
DR OBIOKONKWO, A.C.
[MBBS, U. PHARCOURT]
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY
FEDERAL MEDICAL CENTRE BIRNIN KEBBI
KEBBI STATE

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Outline

Introduction

Pharmacology

Uses in obstetrics and gynaecology

Other uses

Controversies

Conclusion & Recommendations

References

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Introduction

Drug use is almost as old as man. Records -
Sumerians use dating as far back as 5000 B.C.
[1]

Some drugs were found to be harmful, but
others found to be extremely useful

Misoprostol belongs to the useful group and in
2011, was added to the WHO model list of
essential medicines

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Introduction

Developed by G.D. Searle & Company in 1973

Originally approved by the Food and Drug
Administration (FDA) for the prevention of
stomach ulcers in patients taking nonsteroidal
anti-inflammatory drugs

Currently used for a variety on on- and off-label
indications

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Pharmacology
[2]
Synthetic analogue of prostaglandin E
1
(PgE
1
)
Formular – C
22
H
38
O
5
; molar mass – 382.534 g/mol

Routes of admin - oral, vaginal, sublingual,
buccal, rectal

Extensively absorbed, 80 – 90% protein bound

Metabolized in the liver, excreted in urine (80%)

Elimination half life 20 – 40 minutes

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Pharmacology
[2]
15-deoxy-16-hydroxy-16-methyl-PgE1

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Pharmacology
[2]

Cheap and heat-stable, able to stimulate uterine
contractility in early pregnancy & at term

There are no known drug interactions with
misoprostol
[3]

Pregnancy category X

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Pharmacology
[2]

It is considered a teratogen.
[3]
Absolute risk – 1%
-Congenital malformations thought to be due to
vascular disruptions secondary to uterine contractions
caused by misoprostol
-Defects: skull defects, bladder extrophy,
arthrogryposis, CN palsies, facial malformations, limb
defects, Moebius sequence

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Pharmacology
[2]

Adverse effects...
-Uterine hyperstimulation
-Hyperthermia
-Chills
-Vaginal bleeding

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Pharmacology
[2]

...Adverse effects
-Diarrhoea
-Abdominal pain
-Clinical exacerbation of inflammatory bowel disease
-Anaphylaxis

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Use in Obstetrics and Gynaecology

Obstetric uses
-Cervical ripening and induction of labour (IOL)
-Post partum haemorrhage (PPH)

Gynaecological uses
-Termination of pregnancy (medically)
-Cervical ripening before instrumentation

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Cervical ripening and induction of labour

Low dose oral misoprostol (20-25µg 2-hourly) is
safer and more effective than vaginal
misoprostol
[4]

Vaginal misoprostol in doses >25µg 4-hourly is
associated with a greater risk of uterine
hyperstimulation
[4]

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Cervical ripening and induction of labour

Misoprostol vs placebo...
-10 trials
[4]
involving 1141 women
-Vaginal misoprostol – less failure to deliver within 24
hours
-Uterine hyperstimulation without foetal heart
changes was increased

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Cervical ripening and induction of labour

...Misoprostol vs placebo
-Oral misoprostol - more likely to deliver in 24 hours,
less need for oxytocin use, lower caesarean delivery
rate

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Cervical ripening and induction of labour

Misoprostol vs oxytocin...
-25 trials
[4]
involving 3074 participants
-Vaginal misoprostol more effective than oxytocin for
IOL
-Use of less than 50µg misoprostol showed no
reduction in failure to deliver within 24 hours

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Cervical ripening and induction of labour

...Misoprostol vs oxytocin
-Uterine hyperstimulation without foetal heart
changes commoner in the misoprostol group
-No difference in perinatal or maternal adverse
outcome between groups
-Increase in meconium-stained liquor in oral
misoprostol vs intravenous oxytocin

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Cervical ripening and induction of labour

Misoprostol vs other prostaglandins (especially
dinoprostone)...
-38 trials,
[4]
7022 participants
-Failure to deliver vaginally within 24 hours less in
misoprostol group
-Uterine hyperstimulation with FHR changes and
meconium-stained liquor more with misoprostol

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Cervical ripening and induction of labour

...Misoprostol vs other prostaglandins
-Oral misoprostol less likely than vaginal dinoprostone
have a caesarean delivery
-Oral misoprostol group less likely to deliver within 24
hours vs vaginal dinoprostone

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Cervical ripening and induction of labour

Recommended dosing
[5]
-Intravaginally, 25µg 6-hourly or
-Orally, 25µg 2-hourly
-Contraindicated in women with a previous uterine
scar

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Safe single doses of vaginal misoprostol for
producing uterine contractions at various
gestations

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Post-partum haemorrhage

Useful for both the prevention and treatment of
PPH

For treatment, evidence
[6]
shows that...
-Oral route of admin fast uptake, but shortest duration
of action

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Post-partum haemorrhage

...For treatment, evidence
[6]
shows that
-Rectal route has slow uptake with a prolonged
duration of action
-Buccal and sublingual routes have rapid uptake,
prolonged duration of action and greatest total
bioavailability

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Post-partum haemorrhage

PPH prophylaxis
[7]
-Oral dose of 600µg stat
-Not as effective as oxytocin
-Exclude second twin before administration

PPH treatment
[8]
-Sublingual dose of 800µg stat

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Termination of pregnancy

First trimester medical abortion...
-Indicated for induced, missed or incomplete abortion
-FDA-approved regimen can be initiated up to 49 days
from 1
st
day of last menstrual period
-Involves use of misoprostol alone or in combination
with mifepristone or methotrexate

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Termination of pregnancy

...First trimester medical abortion
-Mifepristone, 600µg PO stat + misoprostol, 400µg PO
on day 3
-Methotrexate, 50 mg/m
2
IM + misoprostol 800µg PV
on day 5

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Termination of pregnancy

Second trimester...
[9]
-Indicated for IUFD and congenital anomalies
incompatible with life
-Vaginal misoprostol more effective than oral
misoprostol
[10]
in T2 and T3
-Also as effective as the traditionally used gemeprost
-IUFD:13-17 weeks, 200µg 6-hourly vaginally x4 max

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Termination of pregnancy

...Second trimester
[9]
-18-26 weeks. 100µg 6-hourly vaginally, x4 max
-Interruption of pregnancy: 400µg vaginally or
sublingually 3-hourly x5 max
-Caution in women with uterine scars

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Cervical ripening pre-instrumentation
[9]

First trimester
-Vaginally or sublingually, 400µg 3 hours prior to
procedure
-Indications

Insertion of IUD

Surgical termination of pregnancy

Hysteroscopy

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Other uses

Currently ONLY approved by the Food and Drug
Administration (FDA) for prevention of gastric
ulcers resulting from chronic administration of
non-steroidal anti-inflammatory drugs eg in the
elderly

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Known issues in our environment...

Difficulty in compounding recommended dose

Easy access to misoprostol by health and non-
health workers

Self administration by some at home for self
induction of labour or abortions

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...Known issues in our environment

The small chance of developing Moebius
syndrome in failed misoprostol-induced abortion

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Controversies

Manufacturers of Cytotec™ issued letters in
2000 warning against use of misoprostol in
pregnant women

Safety of misoprostol versus other agents used
for IOL

Political tussle of pro- versus anti-abortion
hardliners

Mifepristone versus misoprostol for TOP

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Recommendations

Consider oral route for IOL with misoprostol

Evidence
[6]
shows the sublingual route to be the
most promising. Consider this for treatment of
PPH

Consider local compounding of oral misoprostol
to easily administer the recommended dosage

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Conclusion

The discovery of misoprostol could easily be
regarded as one of the best things in modern
medicine secondary to antibiotics

Though the use in ObGyn is off-label, it's legal
and have been highly recommended by several
authorities

Misoprostol use in obstetrics is a double-edged
sword – our duty

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THANK YOU FOR LISTENING!

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References
1. The Schaffer Library of Drug Policy: A summary of Historical events.
Available from http://www.druglibrary.org/schaffer/history/histsum.htm
2.Hoogerwerf WA, Pasricha JP. Pharmacotherapy of gastric acidity,
peptic ulcers, and gastroesophageal reflux disease. In: Brunton LL,
Lazo JS, Parker KL, editors. Goodman & Gilman's The Pharmacological
Basis of Therapeutics. 11
th
ed. Chicago: McGraw-Hill; 2006
3.Goldberg AB, Greenberg MB, Darney PD. Misoprostol and pregnancy. N
Engl J Med. 2001; 334:38-47
4.Abdel-Aleem H. Misoprostol for cervical ripening and induction of
labour: RHL commentary (last revised: 1 May 2011). The WHO
Reproductive Health Library; Geneva: World Health Organization.
5.WHO recommendations for induction of labour, 2011. Retrieved from
http://www.misoprostol.org/dosage-guidelines/

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References
6. Hofmeyr GJ, Walraven G, Gulmezoglu AM, Maholwana B, Alfirevic Z,
Villar J. Misoprostol to treat postpartum haemorrhage: a systematic
review. BJOG 2005; 112: 547-53 doi: 10.1111/j.1471-
0528.2004.00512.x pmid: 15842275.
7.FIGO Guidelines: Prevention of PPH with misoprostol, 2012. Retrieved
from http://www.misoprostol.org/dosage-guidelines/
8.FIGO Guidelines: Treatment of PPH with misoprostol, 2012. Retrieved
from http://www.misoprostol.org/dosage-guidelines/
9.WHO/RHR. Safe abortion: technical and policy guidelines for health
systems (2nd edition), 2012. Retrieved from
http://www.misoprostol.org/dosage-guidelines/
10. Matthews JE. Misoprostol for induction of labour to terminate
pregnancy in the second or third trimester for women with a fetal
anomaly or after intrauterine foetal death: RHL commentary (last
revised: 1 October 2010). The WHO Reprobuctive Health Library; Geneva:
World Health Organization.