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
 Costa SH, Vessey MP. Misoprostol and illegal abortion in Rio de
summary table of the recommended dosages in each chapter
Janeiro, Brazil. Lancet May 15 1993;341(8855):1258–61.
 Miller S, Lehman T, Campbell M, Hemmerling A, Anderson SB,
Some concepts are repeated in all articles, such as
Rodriguez H, et al. Misoprostol and declining abortion-relatedmorbidity in Santo Domingo, Dominican Republics: a temporal
contraindications for the use of misoprostol. This is done so
association. BJOG 2005;112:1291–6.
that each article can be consulted independently from the
 Mariani Neto C, Leão EJ, Barreto MCP, Kenj G, Aquino MM, Tuffi
others. The exception is drug pharmacology, which called for
VHB. Uso do misoprostol para indução do parto com feto morto.
a whole separate chapter. For the sake of brevity, we give no
specific guidance on counseling before the drug's use. How-
 Bugalho A, Bique C, Machungo F, Faundes A. Induction of labor
ever, it should be taken as read that all patients will benefit
with intravaginal misoprostol in intrauterine fetal death. Am J
from receiving information about the likely course of the
Obstet Gynecol Aug 1994;171(2):538–41.
treatment and possible side-effects.
 Margulies M, Campos Perez G, Voto LS. Misoprostol to induce
No attempt has been made to classify the strength of
labor [letter]. Lancet 1992;339:364.
the evidence available for each indication. However, all
 Grimes DA. Mifepristone (RU 486) for induced abortion.
Womens Health Issues 1993;3(3):171–5.
statements about the use of misoprostol in this supple-
 Bugalho A, Bique C, Machungo F, Faundes A. Low-dose vaginal
ment have been agreed by the authors and submitted to
misoprostol for induction of labor with a live fetus. Int J
the scrutiny of other external experts. The papers on
Gynecol Obstet May 1995;49(2):149–55.
each indication were written by misoprostol experts
 Reichler A, Romem Y, Divon MY. Induction of labor. Curr Opin
brought together by the UNDP/UNFPA/WHO/World Bank
Obstet Gynecol Dec 1995;7(6):432–6.
Special Programme of Research, Development and
 Bauer T, Brown D, Chai L. Vaginal misoprostol for term labor
Research Training in Human Reproduction (HRP) for a
induction. Ann Pharmacother 1997;31:1391–3.
meeting in Bellagio, Italy in February 2007. Funding for
 el Refaey H, Jauniaux E. Methods of induction of labour. Curr
the meeting was provided from various sources including
Opin Obstet Gynecol Dec 1997;9(6):375–8.
HRP, the Rockefeller Foundation, Gynuity Health Projects
 Bugalho A, Bique C, Almeida L, Faúndes A. The effectiveness of
intravaginal misoprostol (Cytotec) in inducing abortion after
eleven weeks of pregnancy. Stud Fam Plann 1993;24(5):
We are aware that some of the recommended doses,
routes of administrations and intervals between doses may
 Murray S, Muse K. Mifepristone and first trimester abortion. Clin
change in the future, when further evidence becomes avail-
Obstet Gynecol Jun 1996;39(2):474–85.
able. This is just part of medical history. The combined
 Scheepers HC, van Erp EJ, van den Bergh AS. Use of misoprostol
contraceptive pills used today are considerably better than
in first and second trimester abortion: a review. Obstet Gynecol
the original pills of the 1950s, but millions of women bene-
fited from those early “imperfect” pills.
 Christin-Maitre S, Bouchard P, Spitz IM. Medical termination of
The intention of this publication is to make accessible to
pregnancy. N Engl J Med Mar 30 2000;342(13):946–56.
our colleagues throughout the world a synthesis of the
 Has R, Batukan C, Ermis H, Cevher E, Araman A, Kilic G, et al.
Comparison of 25 and 50 ug vaginally administered misoprostol
current knowledge on the use of this drug. It is hoped that
for preinduction cervical ripening and labor induction. Gynecol
this will avoid dangerous misuse and improve practice with a
view to reducing maternal morbidity and mortality.
 Perry KG, Larmon JE, May WL, Robinette LG, Martin RW.
Cervical ripening: a randomized comparison between intrava-
ginal misoprostol and an intracervical balloon catheter com-bined with intravaginal dinoprostone. Am J Obstet Gynecol1998;178:1333–40.
 Clark S, Blum J, Blanchard K, Galvao L, Fletcher H, Winikoff
 Wing DA, Ham D, Paul RH. A comparison of orally administered
B. Misoprostol use in obstetrics and gynecology in Brazil,
misoprostol with vaginally administered misoprostol for
Jamaica, and the United States. Int J Gynecol Obstet 2002;
cervical ripening and labor induction. Am J Obstet Gynecol
 Fletcher H, Hutchinson S. A retrospective review of pregnancy
 Diro M, Adra A, Gilles JM, Nassar A, Rodriguz A, Salamat S, et al.
outcome after misoprostol (prostaglandin E1) induction of
A double-blind randomized trial of two dose regimen of
labour. West Indian Med J Mar 2001;50(1):47–9.
misoprostol for cervical ripening and labor induction. J Matern
 Hofmeyr GJ, Gulmezoglu AM. Vaginal misoprostol for cervical
ripening and induction of labour (Cochrane Review). The
 Alfirevic Z, Weeks A. Oral misoprostol for induction of labour.
Cochrane Library, Issue 2. Oxford: Update Software; 2002.
Cochrane Database Syst Rev 2006(Issue 2) Art. No.: CD001338,
 Wagner M. Adverse events following misoprostol induction of
labor. Midwifery Today Int Midwife 2004(71):9–12.
 Golberg AB, Greenberg MB, Darney PD. Misoprostol and
 Garris RE, Kirkwood CF. Misoprostol: a prostaglandin E1
pregnancy. N Engl J Med 2001;344:38–47.
analogue. Clin Pharm Sep 1989;8(9):627–44.
 Neilson JP, Hickey M, Vazquez J. Medical treatment for early
 Walt RP. Misoprostol for the treatment of peptic ulcer and
fetal death (less than 24 weeks). Cochrane Database Syst Rev
antiinflammatory-drug-induced gastroduodenal ulceration.
N Engl J Med Nov 26 1992;327(22):1575–80.
 Barradell LB, Whittington R, Benfield P. Misoprostol: pharma-
 Clark W, Shannon C, Winikoff B. Misoprostol for uterine
coeconomics of its use as prophylaxis against gastroduodenal
evacuation in induced abortion and pregnancy failure. Expert
damage induced by nonsteroidal anti-inflammatory drugs.
Rev Obstet Gynecol 2007;2(1):67–108.
Pharmacoeconomics Feb 1993;3(2):140–71.
 Derman RJ, Kodkany BS, Goudar SS, et al. Oral misoprostol in
 Barbosa RM, Arilha M. The Brazilian experience with Cytotec.
preventing postpartum haemorrhage in resource-poor commu-
nities: a randomized controlled trial. Lancet 2006;368:1248–53.
 Hoj L, Cardosa P, Nielsen BB, Hvidman L, Nielsen J, Aaby P.
 McManus A, Herring C, Weeks A. What proportion of antenatal
Effect of sublingual misoprostol on severe postpartum haemor-
prescriptions are licensed at Liverpool Women's’ Hospital? Data
rhage in a primary health centre in Guinea–Bissau: randomized
presented at British International Congress of Obstetrics and
double blind clinical trial. BMJ 2005;331:723.
 Briozzo L, Vidiella G, Rodriguez F, Gorgoroso M, Faúndes A, Pons
 USFDA. “Off-label” and Investigational Use of Marketed Drugs,
JE. A risk reduction strategy to prevent maternal deaths asso-
Biologics and Medical Devices. Guidance for Institutional
ciated with unsafe abortion. Int J Gynecol Obstet Nov 2006;95
Review Boards and Clinical Investigators: 1998 Update. Avail-
 Faúndes A, Santos LC, Carvalho M, Gras C. Post-abortion
complications after interruption of pregnancy with misopros-
 Faundes A, editor. Uso De Misoprostol En Obstetricia Y
tol. Adv Contracep 1996;12(1):1–9.
Ginecologia. Federacion Latinoamericana De Sociedades De
 Viggiano M, Faúndes A, Borges AL, Viggiano ABF, Souza GR,
Obstetricia Y Ginecologia (FLASOG); 2005.
Rabello I. Disponibilidade de misoprostol e complicações de
 Abdel-Aleem H. Misoprostol for labour induction. Reproductive
aborto provocado em Goiana. J Bras Ginecol 1996;106(3):
Health Library commentary, vol. 7. Oxford: Reproductive
 American College of Obstetricians and Gynecologists. New US
Food and Drug Administration Labelling on Cytotec (misopros-tol) Use and Pregnancy, vol. 283. ACOG Comm Opin; 2003.
 World Health Organization. 15th WHO Model List of
Essential Medicines. Geneva: World Health Organization;
 Weeks AD, Fiala C, Safar P. Misoprostol and the debate over
off-label drug use. BJOG: Int J Obstet Gynaecol 2005;112:
Sunflower Facts The sunflower is a distinctive, flowering plant ( Helianthus annuus L. ), the seeds of which contain a valuable edible oil that contains more Vitamin E than any other vegetable oil. Most sunflower oil is used in food products. The seeds of confection varieties of sunflower are also sold for human consumption and birdseed. Industry Overview U.S. sunflower oil crushers can
Schweinegrippe (Influenza A/H1N1) Die Schweinegrippe ist eine Infektion mit Viren vom Typ Influenza A (H1N1), die inden letzten Tagen vor allem in Mexiko und in den USA aufgetreten ist. Mittlerweilewurden auch Fälle aus anderen Teilen der Welt gemeldet. Es handelt sich um einneuartiges Schweineinfluenzavirus, das nicht nur vom Schwein auf den Menschen,sondern auch von Mensch zu Mensc