International Journal of Gynecology and Obstetrics (2007) 99, S156–S159
a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m
w w w. e l s e v i e r. c o m / l o c a t e / i j g o
Although misoprostol is generally not registered for repro-
experiences have been described in other Latin American
ductive health use, it is widely used by gynecologists and
obstetricians. In a survey on the use of misoprostol con-
Misoprostol's undisputed ability to bring on uterine
ducted in three contrasting countries (Brazil, Jamaica and
contractions led to it being evaluated as a means of inducing
the USA), 61% of obstetricians and gynecologists stated that
abortion or labor with a dead or live fetus, or
they used it to evacuate the uterus after intrauterine fetal
to interrupt pregnancy Its potential was especially
death, 57% used it for missed abortions, and 46% to induce
promising in the developing world where maternal mortality
labor Its popularity may be accounted for by the fact that
is high and where an effective, low-cost and stable prosta-
it is as effective as the best available prostaglandin at soft-
glandin is urgently needed. The benefits of misoprostol in
ening the cervix and producing contractions of the uterus,
settings with few resources have since been widely demon-
while at the same time being low-cost and heat-stable.
strated. It has been possible to reduce failed inductions and
The absence of registration for its obstetrical and gyne-
the proportion of cesarean sections and it has
cological applications is an important problem. The pharma-
facilitated the difficult challenge of evacuating a dead fetus
ceutical industry is normally responsible for informing
during the second trimester of pregnancy, substituting
physicians about drugs' indications, effectiveness, correct
methods that carry a high risk of morbidity and mortality
dosages, route of administration, dosage interval, contra-
It has also proved its capacity to prevent postpartum
indications, precautions, side-effects and management of
hemorrhage in situations where oxytocin is not available or
complications. However, as misoprostol is generally not re-
may lose effectiveness due to high ambient temperatures
gistered for reproductive health indications, the industry has
and there is also now evidence to correlate the
neither provided this information for physicians nor pack-
increase in its use with the reduction of morbidity and
aged the drug in appropriate dosages. The result is that this
mortality associated with abortion in countries with restric-
drug is used in many different ways according to informal
local protocols. While this may not be a serious problem in
In spite of all these advantages, misoprostol has not been
early pregnancy, the use of too high a dose in late pregnancy
approved for use in gynecology or obstetrics in most
can have serious consequences. In induction of labor, for
countries. However, there are signs that health regulators
example, too high a dose of misoprostol may cause uterine
are embracing the use of misoprostol. In 2003, the use of
hyperstimulation and rupture of the uterus, thus jeopardiz-
misoprostol in combination with mifepristone was approved
ing the life of the mother and of the fetus
by the United States Food and Drug Administration for the
Misoprostol is an analogue of prostaglandin E1 (PG E1)
induction of abortion and misoprostol has been added
which was registered in many countries during the second
to the World Health Organization (WHO) Model List of
half of the 1980s under the proprietary name Cytotec
Essential Drugs for the induction of labor and abortion
(Pharmacia), for the treatment of peptic ulcers, particularly
In 2006, the government of Nigeria registered misoprostol for
those caused by non-steroidal anti-inflammatory drugs
the prevention and treatment of postpartum hemorrhage,
Its use for this purpose is contraindicated for pregnant
and a national distribution program is underway in Ethiopia
women as it may cause uterine contractions and miscarriage.
In Brazil, as in many other countries where abortion is
exclusive rights to misoprostol ran out in 2005, and a number
illegal, employees of retail pharmacies are accustomed to
of generic alternatives to Cytotec are now being produced.
selling a wide range of drugs to “bring on periods”. In the
Misoprostol 200 μg tablets are now produced in France,
1980s they realized that the uterine “side-effect” of Cytotec
China, Brazil and Taiwan, and 25 μg vaginal pessaries are
made it a highly effective drug for “bringing on periods” in
cases of delayed menses. The knowledge that misoprostol
was very effective at causing abortions spread rapidly and,
The absence of clear guidance relating to use of
by the end of the 1980s, a high proportion of clandestine
misoprostol in gynecology and obstetrics has meant that
abortions in Brazil were induced by misoprostol . Similar
physicians and their patients run the risk of inappropriate
0020-7292/$ - see front matter 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.
All rights reserved.
use, with potentially severe consequences for both woman
ogy and obstetrics in this supplement is to enable practi-
and fetus. It also places the attending physicians at risk of
tioners to use the drug safely outside the approved
litigation as, in the absence of a license for use in pregnancy,
indications, while being well informed about the product,
legal liability rests with the prescriber.
to base its use on firm scientific rationale and on soundmedical evidence. Guidelines for misoprostol use in repro-
ductive health are available in South America and on theinternet (but it is hoped that this
supplement will make knowledge about optimal misoprostoldosages more widely available.
Use of drugs for indications other than those approved (‘off-label’ use) is common practice in obstetrics . In a recentstudy of 17,000 consecutive antenatal prescriptions in a large
UK government hospital, only 1% of drugs were unlicensedHowever, 75% of all prescriptions were ‘off-label’, most
This supplement is designed to provide guidance to help our
of which would be considered safe for use in pregnancy. They
fellow gynecologists and obstetricians to take decisions on
included betamethasone (for the prevention of respiratory
treatment for a number of specific conditions. This requires
distress syndrome in premature neonates), erythromycin
an evaluation of the evidence and a weighing up of the
(for the prevention of chorioamnionitis after ruptured mem-
potential risks and benefits of the drug's use in each specific
branes) and magnesium sulfate (for eclampsia). Only 10% of
the drugs prescribed were considered high risk. ‘Off-label’
Misoprostol has a large number of potential uses. In this
therapy is also accepted, for example, by the United States
supplement, a team of experts has assessed the existing
Food and Drug Administration, which stated, “Good medical
evidence and has suggested an optimal dose and route. In
practice and the best interests of the patient require that
clinical practice, however, it is for each physician to decide
physicians use legally available drugs … according to their
how best to apply it in his or her own practice, depending on
best knowledge and judgment. If physicians use a product
the circumstances of each individual case
for an indication not in the approved labeling, they have the
In an effort to include the different uses of misoprostol in
responsibility to be well informed about the product, to
gynecology and obstetrics, this supplement includes the fol-
base its use on firm scientific rationale and on sound medical
lowing articles: “pharmacokinetics and basic science”; “cer-
evidence, and to maintain records of the product's use and
vical priming”; “induced abortion in 1st trimester”;
“induced abortion in 2nd trimester”; “incomplete abortion”;
Our objective in publishing the essential points of our
“missed abortion”; “early embryonic loss”; “intrauterine
existing knowledge about the use of misoprostol in gynecol-
fetal death”; “induction of labor with a live fetus”, and
Misoprostol dosages for reproductive health
Ideally used 48 h after mifepristone 200 mg
Leave to work for 1–2 weeks (unless heavy
Use 200 μg only in women with cesarean scar.
Ideally used 48 h after mifepristone 200 mg
Reduce doses in women with previous cesarean
25 μg vaginally 4-hrly OR 50 μg orally Do not use if previous cesarean section
Not as effective as oxytocin or ergometrine.
Exclude second twin before administration.
Do not repeat within 2 h
Limited evidence for benefit — use conventionaloxytocics first
400 μg vaginally 3 h before procedure Use for insertion of intrauterine device, surgical
termination of pregnancy, dilatation andcurettage, hysteroscopy
Wallchart with summary of misoprostol dosages for reproductive health indications (stat = single dose taken immediately, PPH = postpartumhemorrhage) International Journal of Gynecology and Obstetrics 2007
“prevention and treatment of postpartum hemorrhage”. A
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Some concepts are repeated in all articles, such as
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others. The exception is drug pharmacology, which called for
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a whole separate chapter. For the sake of brevity, we give no
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 Bugalho A, Bique C, Machungo F, Faundes A. Induction of labor
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Clinical Infectious Diseases Advance Access published September 9, 2012 Clinical Practice Guideline for the Diagnosisand Management of Group A StreptococcalPharyngitis: 2012 Update by the InfectiousDiseases Society of AmericaaStanford T. Shulman,1 Alan L. Bisno,2 Herbert W. Clegg,3 Michael A. Gerber,4 Edward L. Kaplan,5 Grace Lee,6Judith M. Martin,7 and Chris Van Beneden81Department of Pediat
Kjære venner! Først av alt vil vi få ønske dere alle et Godt og velsignet år 2006!! Vi kan se tilbake på året som gikk, takke for Guds trofasthet og hjelp, men også se framover med håp og forventning. Guds Ord står fast og Herren har lovt at Hans miskunnhet ikke er forbi. Nei, den er ny for hver morgen, for hvert år. Klages. 3,22-23. Er ikke det fantastisk!! Det gir i alle fall meg oppm