International Journal of Gynecology and Obstetrics (2006) 94 (Supplement 2), S149-- S150 The safety of misoprostol Anke Hemmerling * University of California, Berkeley, School of Public Health, 513 Warren Hall, Berkeley,CA 94720-6390, USA
Misoprostol is currently on the WHO Essential Drug
with supportive care within 12 hours. Bentov 
List for treatment of gastric ulcers, for induced
concludes that his case of overdose with 42 tablets
abortion in combination with mifepristone, and
(8.4 mg) over three days "illustrates the relative
more recently for induction of labor. The WHO will
review its role as an essential drug for control of
The literature also reports one case of severe
postpartum hemorrhage (PPH) in early 2007. Rel-
hyperthermia postpartum reaching 41.9°C follow-
evant data on the safety of misoprostol has accu-
ing a normal dose of 800 mcg of oral misopros-
mulated since the introduction of the drug in the
tol and requiring intensive supportive care . Al-
late 1980s. Since then, millions of individuals world-
though no other extreme cases of pyrexia are re-
wide have used up to four tablets (800 mcg) daily for
ported, several studies on PPH using oral misopros-
treatment and prevention of gastric ulcer.
tol of 400-- 600 mcg describe transient pyrexia of
Multi-center trials following thousands of users
38°C (100.4°F) or higher [10-- 14]. In these trials
[1,2], as well as a review of the worldwide safety
a limited number of parturients (5--28%) were af-
data  and a Cochrane Review in 2002  failed to
fected and very few sustained a fever of 39--40°C.
report any misoprostol related deaths or side effects
The temperature elevations generally last 1-- 2 hours
severe enough to demand the cessation of treat-
and then rapidly cease with minor or no interven-
ment. Common side effects for long term misopros-
tion. Oral and sublingual routes of administration
tol users with gastric ulcers were the same as seen
seem to trigger pyrexia more frequently than the
in some women treated for PPH -- and include chills,
Interestingly, pyrexia after misoprostol adminis-
Four cases of acute toxicity after accidental or
tration also seems to occur in women using the drug
intentional overdose with misoprostol are described
late in gestation and at delivery but rarely in ulcer
in the peer-reviewed literature, two of them in
patients or women in early pregnancy. The author is
women beyond 30 weeks of pregnancy [5--8]. Af-
not aware of a conclusive explanation for this phe-
ter ingesting a large number of misoprostol tablets,
nomenon at this time. Including careful monitoring
sometimes mixed with other medication, tachycar-
of body temperature into the design of future miso-
dia, nausea and abdominal pain and, in some cases,
prostol studies would be helpful, and users should
hyperthermia was reported, although the authors
be taught simple techniques of diagnosing and treat-
of these reports emphasize the complete resolution
ing transient fevers associated with misoprostol use.
Among more than two dozen studies of the use
* Corresponding author. Tel.: +1 510 643-7627.
of misoprostol for PPH, death was not reported to
E-mail: email@example.com (A. Hemmerling).
have occurred during these trials. In four other stud-
0020-7292/$ -- see front matter 2006 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
ies, deaths were reported, and for six of the total
intestinal complications in patients with rheumatoid
of eight cases detailed information was presented.
arthritis receiving nonsteroidal anti-inflammatory drugs.
One woman died of a malaria-related disseminated
A randomized, double-blind, placebo-controlled trial. AnnIntern Med 1995;123(4):241-- 9.
intravascular coagulation after average blood loss.
 Herting RL and Clay GA. Overview of clinical safety with
A high risk multiparous woman with a low prena-
misoprostol. Dig Dis Sci 1985;30(11 Suppl):185S-- 93S.
tal hemoglobin level died of severe PPH before she
 Wildeman RA. Focus on misoprostol: review of worldwide
reached the hospital . One woman died sec-
safety data. Clin Invest Med 1987;10(3):243-- 5.
ondary to a coagulopathy after hysterectomy and
 Rostom A, Dube C, Wells G, Tugwell P, Welch V, Jolicoeur E,
et al. Prevention of NSAID-induced gastroduodenal ulcers.
consequent re-laparotomy 48 hours after delivery.
Cochrane Database Syst Rev 2002(4): CD002296.
Another woman with a previous C-section died of
 Graber DJ and Meier KH. Acute misoprostol toxicity. Ann
PPH and did not receive an autopsy to evaluate the
possibility of a ruptured scar. A third woman in the
 Bond GR and Van Zee A. Overdosage of misoprostol in preg-
same trial died of severe blood loss caused by a torn
nancy. Am J Obstet Gynecol 1994;171(2):561-- 2.
 Bentov Y, Sheiner E and Katz M. Misoprostol overdose dur-
cervix after labor induction and postpartum appli-
ing the first trimester of pregnancy. Eur J Obstet Gynecol
cation of several uterotonics . In another trial,
a woman died suddenly after severe blood loss 90
 Austin J, Ford MD, Rouse A and Hanna E. Acute intravagi-
minutes after delivery of an inconclusive cause of
nal misoprostol toxicity with fetal demise. J Emerg Med
death . In a fourth trial with two cases no reason
 Chong YS, Chua S and Arulkumaran S. Severe hyperther-
for death was specified by the authors . None of
mia following oral misoprostol in the immediate postpar-
the cases with fatal complications were associated
tum period. Obstet Gynecol 1997;90(4 Pt 2):703-- 4.
with misoprostol side effects such as severe hyper-
 Chandhiok N., Dhillon BS, Datey S, Mathur A and Saxena
NC. Oral misoprostol for prevention of postpartum hem-
In conclusion, there have been no serious side ef-
orrhage by paramedical workers in India. Int J GynaecolObstet 2006;92(2):170-- 5.
fects among millions of ulcer patients using miso-
 Gulmezoglu AM, Villar J, Ngoc NT, Piaggio G, Carroli G,
prostol. The few reported cases of extreme over-
Adetoro L, et al. WHO multicentre randomised trial of
dose experienced a rapid recovery. None of the fatal
misoprostol in the management of the third stage of
cases among misoprostol recipients in PPH trials is
labour. Lancet 2001;358(9283):689-- 95.
definitively linked to a misoprostol side effect. The
 Hofmeyr GJ, Ferreira S, Nikodem VC, Mangesi L, Singata M,
Jafta Z, et al. Misoprostol for treating postpartum haem-
occurrence of transient pyrexia of 38--40°C among
orrhage: a randomized controlled trial [ISRCTN72263357].
a minority of women receiving misoprostol for PPH
BMC Pregnancy Childbirth 2004;4(1):16.
should be monitored in the future and clearly ad-
 Lumbiganon P, Hofmeyr J, Gulmezoglu AM, Pinol A and Vil-
dressed during the training of community health
lar J. Misoprostol dose-related shivering and pyrexia in the
workers. The data from several dozen trials com-
third stage of labour. WHO Collaborative Trial of Misopros-tol in the Management of the Third Stage of Labour. Br J
pleted at this time -- combining the experience of
Obstet Gynaecol 1999;106(4):304-- 8.
more than 17,000 women who have used misoprostol
 Walraven G, Blum J, Dampha Y, Sowe M, Morison L,
to control PPH -- shows that the drug has a remark-
Winikoff B, et al. Misoprostol in the management of the
ably benign safety profile and would appear safe to
third stage of labour in the home delivery setting in rural
use outside of hospital settings. This stable, low cost
Gambia: a randomised controlled trial. Bjog 2005;112(9):1277-- 83.
and easy-to-use medication has the potential to im-
 Hoj L, Cardoso P, Nielsen BB, Hvidman L, Nielsen J
prove significantly the control of postpartum hem-
and Aaby P. Effect of sublingual misoprostol on severe
postpartum haemorrhage in a primary health centre inGuinea-Bissau: randomised double blind clinical trial. BMJ2005;331(7519):723. References
 Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers
BJ, Bittman RM, et al. Misoprostol reduces serious gastro-
Economic Evaluation of Treatment Strategies for Benign Prostatic Hyperplasia—Is Medical Therapy More Costly in the Long Run? Christopher S. Saigal,* Mehran Movassaghi, Jennifer Pace, Geoffrey Joyce and the Urologic Diseases in America Project From the Department of Urology, University of California-Los Angeles Medical Center, Los Angeles, California Purpose: Although medical therapy fo
JS'12, Cnam Paris, 3-4 Avril 2012 Effets comportementaux d’une exposition de rats Wistar mâles adultes à des ondes électromagnétiques impulsionnelles de forte puissance (3 GHz) Behavioural effects of radar type (3 GHz) microwave exposure: study on male adult Wistar rats Céline Crétallaz*, Ioannis Lamproglou**, Christine Amourette*, Michel Diserbo*, William Fauquette*,