Misoprostol use in Obstetrics and Gynaecology

MISOPROSTOL USE IN OBSTETRICS AND GYNAECOLOGY

DR OBIOKONKWO, A.C.[MBBS, U. PHARCOURT]

DEPARTMENT OF OBSTETRICS AND GYNAECOLOGYFEDERAL MEDICAL CENTRE BIRNIN KEBBI

KEBBI STATE

05/03/23 facebook.com/imezi2

Outline

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


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


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


Pharmacology [2]

Synthetic analogue of prostaglandin E1 (PgE1)

Formular – C22H38O5 ; 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


Pharmacology [2]

15-deoxy-16-hydroxy-16-methyl-PgE1


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


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


Pharmacology [2]

Adverse effects...

Uterine hyperstimulation

Hyperthermia

Chills

Vaginal bleeding


Pharmacology [2]

...Adverse effects

Diarrhoea

Abdominal pain

Clinical exacerbation of inflammatory bowel disease

Anaphylaxis


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


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]



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



...Misoprostol vs placebo

Oral misoprostol - more likely to deliver in 24 hours, less need for oxytocin use, lower caesarean delivery rate



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



...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



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



...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



Recommended dosing [5]

Intravaginally, 25µg 6-hourly or

Orally, 25µg 2-hourly

Contraindicated in women with a previous uterine scar


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

gestations


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



...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



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


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



...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



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



...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


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


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


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


...Known issues in our environment

The small chance of developing Moebius syndrome in failed misoprostol-induced abortion


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


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


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


THANK YOU FOR LISTENING!


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/

http://www.druglibrary.org/schaffer/history/histsum.htm

http://www.misoprostol.org/dosage-guidelines/


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.




Health & Medicine

Misoprostol use in Obstetrics and Gynaecology