Misoprostol use in Obstetrics and Gynaecology

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

04/29/16 facebook.com/imezi
2
Outline

Introduction

Pharmacology

Uses in obstetrics and gynaecology

Other uses

Controversies

Conclusion & Recommendations

References

3
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

4
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

5
Pharmacology [2]
 Synthetic analogue of prostaglandin E1
(PgE1
)
 Formular – C22
H38
O5
; 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

6
Pharmacology [2]
15-deoxy-16-hydroxy-16-methyl-PgE1

7
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

8
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

9
Pharmacology [2]

Adverse effects...
− Uterine hyperstimulation
− Hyperthermia
− Chills
− Vaginal bleeding

10
Pharmacology [2]

...Adverse effects
− Diarrhoea
− Abdominal pain
− Clinical exacerbation of inflammatory bowel disease
− Anaphylaxis

11
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

12
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]

13

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

14

...Misoprostol vs placebo
− Oral misoprostol - more likely to deliver in 24 hours,
less need for oxytocin use, lower caesarean delivery
rate

15

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

16

...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

17

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

18

...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

19

Recommended dosing [5]
− Intravaginally, 25µg 6-hourly or
− Orally, 25µg 2-hourly
− Contraindicated in women with a previous uterine
scar

20
Safe single doses of vaginal misoprostol for
producing uterine contractions at various
gestations

21
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

22

...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

23

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

24
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 1st
day of last menstrual period
− Involves use of misoprostol alone or in combination
with mifepristone or methotrexate

25

...First trimester medical abortion
− Mifepristone, 600µg PO stat + misoprostol, 400µg PO
on day 3
− Methotrexate, 50 mg/m2
IM + misoprostol 800µg PV
on day 5

26

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

27

...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

28
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

29
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

30
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

31
...Known issues in our environment

The small chance of developing Moebius
syndrome in failed misoprostol-induced abortion

32
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

33
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

34
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

35
THANK YOU FOR LISTENING!

36
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. 11th
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/

37
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

Misoprostol use in Obstetrics and Gynaecology

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