Instructions for use
Misoprostol for treatment of postpartum hemorrhage
BACKGROUND
Misoprostol is a prostaglandin E1 analog developed for prevention of gastric ulcers due to chronic use of non-steroidal anti-inflammatory drugs (NSAIDs). As misoprostol also induces uterine contractions, it is commonly used for obstetric indications. Postpartum hemorrhage (PPH) is excessive bleeding following birth and occurs in ~5-10% of deliveries. Approximately 70% of PPH cases are due to inadequate uterine contractions. The recommended treatment for PPH is oxytocin which requires parenteral administration, trained providers, and cold storage and is thus not feasible in some contexts. Misoprostol is a tablet that is easily administered and stable at ambient temperatures. The following information is presented for the guidance of healthcare providers where access to oxytocin is limited.
INDICATION AND USAGE
Misoprostol is indicated for treatment of postpartum hemorrhage suspected to be due to uterine atony after vaginal delivery.
Use of misoprostol for PPH treatment is effective in reducing postpartum blood loss following vaginal delivery. A single dose of misoprostol has been shown to control active bleeding within 20 minutes of administration for approximately 90% of women in hospital settings.
CONTRAINDICATIONS
History of allergy to misoprostol or other prostaglandins.
PRECAUTIONS
Providers should try to determine that the PPH is not due to factors besides uterine atony (tears, clotting disorders, retained tissue).
Providers should be prepared to manage moderate/severe shivering and fever.
If misoprostol was used for prevention of PPH during the third stage of labor, it is recommended that oxytocin or ergometrine be given to treat women with continued bleeding. If other uterotonics are not available, misoprostol can be used but side effects may be increased.
Small amounts of misoprostol or its active metabolite may appear in breast milk. No adverse effects on nursing infants have been reported.
EFFECTS AND SIDE EFFECTS
Prolonged or serious side effects are rare.
SHIVERING
Shivering is the most common side effect of misoprostol following its postpartum administration. Shivering usually occurs within the first hour of taking misoprostol. This side effect is transient.
FEVER
Fever is less common than shivering and does not necessarily indicate infection. Elevated body temperature is often preceded by shivering, peaks 1-2 hours after taking misoprostol, and gradually subsides within 2-6 hours. An antipyretic and cool compress can be used for relief of fever, if needed. If fever or shivering persists beyond 24 hours, infection should be ruled out.
DIARRHEA, NAUSEA AND VOMITING
Diarrhea may also occur but should resolve within a day. Nausea and vomiting may occur and will resolve 2-6 hours after taking misoprostol. An antiemetic can be used if needed.
DOSAGE AND ADMINISTRATION
The recommended regimen for treatment of postpartum hemorrhage is a single dose of 800 mcg misoprostol sublingually (under the tongue).
Notes:
Adjunct use of misoprostol for PPH treatment (simultaneous administration of misoprostol and standard uterotonics) has been shown to offer no beneficial effect and is associated with increased side effects.
SUGGESTED CITATION
Instructions for Use: Misoprostol for Treatment of Postpartum Hemorrhage. Gynuity Health Projects. February 2011.
For more information, refer to www.gynuity.org
This document will be periodically reviewed and updated with current information and research developments.
© 2011 Gynuity Health Projects.
February 2011
REFERENCES
Aronsson, A., Fiala, C., Stephansson, O., Granath, F., Watzer, B., Schweer, H., et al. (2007). Pharmacokinetic profiles up to 12 h after administration of vaginal, sublingual and slow-release oral misoprostol.
Human Reproduction (Oxford, England), 22(7), 1912-1918. Blum, J., Alfirevic, Z., Walraven, G., Weeks, A., & Winikoff, B. (2007).Treatment of postpartum hemorrhage with misoprostol. International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics, 99 Suppl 2, S202-5.
Blum, J., Winikoff, B., Raghavan, S., Dabash, R., Ramadan, M. C., Dilbaz, B., et al. (2010). Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: A double-blind, randomised, non-inferiority trial. Lancet, 375(9710), 217-223.
Chong, Y. S., Chua, S., Shen, L., & Arulkumaran, S. (2004). Does the route of administration of misoprostol make a difference? the uterotonic effect and side effects of misoprostol given by different routes after vaginal delivery. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 113(2), 191-198.
Durocher, J., Bynum, J., Leon, W., Barrera, G., & Winikoff, B. (2010).High fever following postpartum administration of sublingual misoprostol. BJOG: An International Journal of Obstetrics and Gynaecology.
Hofmeyr, G. J., Ferreira, S., Nikodem, V. C., Mangesi, L., Singata, M., Jafta, Z., et al. (2004). Misoprostol for treating postpartum haemorrhage: A randomized controlled trial [ISRCTN72263357].
BMC Pregnancy and Childbirth, 4(1), 16. Hofmeyr, G. J., Gulmezoglu, A. M., Novikova, N., Linder, V., Ferreira, S., & Piaggio, G. (2009).Misoprostol to prevent and treat postpartum haemorrhage: A systematic review and meta-analysis of maternal deaths and dose-related effects. Bulletin of the World Health Organization, 87(9), 666-677.
Lokugamage, A. U., Sullivan, K. R., Niculescu, I., Tigere, P., Onyangunga, F., El Refaey, H., et al. (2001). A randomized study comparing rectally administered misoprostol versus syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage. Acta Obstetricia Et Gynecologica Scandinavica, 80(9), 835-839.
Mousa, H. A., & Alfirevic, Z. (2007). Treatment for primary postpartum haemorrhage. Cochrane Database of Systematic Reviews (Online), (1)(1), CD003249.
Tang, O. S., Gemzell-Danielsson, K., & Ho, P. C. (2007). Misoprostol: Pharmacokinetic profiles, effects on the uterus and side-effects. International Journal of Gynaecology and Obstetrics, 99 Suppl 2, S160-7.
Walraven, G., Dampha, Y., Bittaye, B., Sowe, M., & Hofmeyr, J. (2004). Misoprostol in the treatment of postpartum haemorrhage in addition to routine management: A placebo randomised controlled trial. BJOG : An International Journal of Obstetrics and Gynaecology, 111(9), 1014-1017.
Widmer, M., Blum, J., Hofmeyr, G. J., Carroli, G., Abdel-Aleem, H., Lumbiganon, P., et al. (2010). Misoprostol as an adjunct to standard uterotonics for treatment of post-partum haemorrhage: A multicentre, double-blind randomised trial. Lancet, 375(9728), 1808-1813.
Winikoff, B., Dabash, R., Durocher, J., Darwish, E., Nguyen, T. N., Leon, W., et al. (2010). Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: A double-blind, randomised, non-inferiority trial. Lancet, 375(9710), 210-216.
MISOPROSTOL FOR THE TREATMENT OF POSTPARTUM HEMORRHAGE
Misoprostol has been shown to be an effective treatment for postpartum hemorrhage (PPH) if administered sublingually.
Adapted from image provided courtesy of Ipas
5 things you should know about the sublingual route
1. EVIDENCE-BASED
Two large randomized controlled trials showed the efficacy of 800 mcg of misoprostol given sublingually to treat postpartum hemorrhage. There are no large, randomized clinical trials (RCTs) testing any other route.
2. EASY TO ADMINISTER
When misoprostol is taken sublingually, the woman holds the pills under her tongue for 20 – 30 minutes. Any remaining pill fragments can be swallowed. This route is easy for providers and feasible for women who are unconscious.
3. WORKS QUICKLY
In treating PPH, rapid induction of uterine contractions is desirable and is best achieved through the sublingual route which has the fastest absorption, highest serum levels, and highest bioavailability. In the two large RCTs, misoprostol administered by the sublingual route controlled postpartum hemorrhage within 20 minutes for 9 out of 10 women.
4. MANAGEABLE SIDE EFFECTS
Shivering and fever are common after administration of misoprostol. Studies have shown that these side-effects are transient and easily managed. Vomiting after pills are given sublingually is infrequent and does not interfere with treatment.
5. ACCEPTABLE TO WOMEN
Studies have shown that women are satisfied with sublingual administration of misoprostol and have little difficulty holding the pills under their tongues.