Re: Cytotec
From: Efrain Ramirez (eramirezt@coqui.net)
Fri May 12 06:38:38 2006
Sorry - here is ACOG's response
Committee
Opinion
[PDF format]
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Number 248, December 2000
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Response to Searle's Drug Warning on Misoprostol
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On August 23, 2000, G.D. Searle & Co. issued a letter entitled
"Important Drug Warning Concerning Unapproved Use of Intravaginal or
Oral Misoprostol in Pregnant Women for Induction of Labor or Abortion."
This letter cautions that Cytotec (misoprostol) is indicated for
prevention of nonsteroidal-antiinflammatory-drug-induced gastric ulcers
and states, "...Cytotec administration by any route is contraindicated
in women who are pregnant because it can cause abortion." The letter
further states that Searle has become aware of the drug's use for
induction of labor or as a cervical ripening agent prior to termination
of pregnancy. Moreover, the letter notes serious adverse events,
including uterine hyperstimulation and uterine rupture, which have
resulted in fetal and maternal death. Finally, the company cautions,
"In addition to the known and unknown acute risks to the mother and
fetus, the effect of Cytotec on the later growth, development, and
functional maturation of the child when Cytotec is used for induction of
labor or cervical ripening has not been established."
The American College of Obstetricians and Gynecologists (ACOG) is
concerned about the content, timing, and tone of this letter. Given
that misoprostol is commonly employed in conjunction with mifepristone
(RU 486) to achieve nonsurgical early pregnancy terminations, the
arrival of the Searle letter within weeks of the U.S. Food and Drug
Administration's (FDA) approval of mifepristone could limit the use of
this new option for reproductive choice. Also, although the letter
correctly points out the potentially serious, but relatively rare, risks
of misoprostol when employed for cervical ripening and labor induction,
it fails to comment on the extensive clinical experience with this agent
and the large body of published reports supporting its safety and
efficacy when used appropriately. A recent review of the Cochrane
Pregnancy and Childbirth group trials registry identified 26 clinical
trials of misoprostol for cervical ripening or induction of labor or
both (1). These studies indicate misoprostol is more effective than
prostaglandin E2 in achieving vaginal deliveries within 24 hours and
reduces the need for and total amount of oxytocin augmentation. Although
these studies do suggest misoprostol is associated with a higher
incidence of uterine hyperstimulation and meconium-stained amniotic
fluid, these complications were more common with higher doses(>25 µg) of
misoprostol. Other recent reviews and clinical trials support these
conclusions (2–4). No studies indicate that intrapartum exposure to
misoprostol (or other prostaglandin cervical ripening agents) has any
long-term adverse health consequences to the fetus in the absence of
fetal distress, nor is there a plausible biologic basis for such a
concern.
A review of published reports and of MedWatch, the FDA medical products
reporting program, indicates the vast majority of adverse maternal and
fetal outcomes associated with misoprostol therapy resulted from the use
of doses greater than 25 µg, dosing intervals more frequent than 3–6
hours, addition of oxytocin less than 4 hours after the last misoprostol
dose, or use of the drug in women with prior cesarean delivery or major
uterine surgery. Grand multiparity also appears to be a relative risk
factor for uterine rupture.
Thus, based on recently published series and a detailed review of
adverse outcomes reported to the FDA, the ACOG Committee on Obstetric
Practice strongly endorses its previous conclusion, published in
Committee Opinion Number 228 (November 1999), Induction of Labor with
Misoprostol, which states, "Given the current evidence, intravaginal
misoprostol tablets appear effective in inducing labor in pregnant women
who have unfavorable cervices" (5). Nonetheless, the committee would
like to emphasize that the following clinical practices appear to
minimize the risk of uterine hyperstimulation and rupture in patients
undergoing cervical ripening or induction in the third trimester:
If misoprostol is to be used for cervical ripening or labor induction in
the third trimester, one quarter of a 100-µg tablet (ie, approximately
25 µg) should be considered for the initial dose.
Doses should not be administered more frequently than every 3–6 hours.
Oxytocin should not be administered less than 4 hours after the last
misoprostol dose.
Misoprostol should not be used in patients with a previous cesarean
delivery or prior major uterine surgery.
The use of higher doses of misoprostol (eg, 50 µg every 6 hours) to
induce labor may be appropriate in some situations, although there are
reports that such doses increase the risk of complications, including
uterine hyperstimulation and uterine rupture (6). There is insufficient
clinical evidence to address the safety or efficacy of misoprostol in
patients with multifetal gestations or suspected fetal macrosomia.
In conclusion, the ACOG Committee on Obstetric Practice reaffirms that
misoprostol is a safe and effective agent for cervical ripening and
labor induction when used appropriately. Moreover, misoprostol also
contributes to the obstetrician–gynecologist's resources as an effective
treatment for serious postpartum hemorrhage in the presence of uterine
atony (7–12).
References
Hofmeyr GJ, Gulmezoglu AM. Vaginal misoprostol for cervical ripening
and labour induction in late pregnancy (Cochrane Review). In: The
Cochrane Library, Issue 3, 2000. Oxford: Update Software
Wing DA. Labor induction with misoprostol. Am J Obstet Gynecol
1999;181:339–345
Nunes F, Rodrigues R, Meirinho M. Randomized comparison between
intravaginal misoprostol and dinoprostone for cervical ripening and
induction of labor. Am J Obstet Gynecol 1999;181:626–629
Blanchette HA, Nayak S, Erasmus S. Comparison of the safety and
efficacy of intravaginal misoprostol (prostaglandin E1) with those of
dinoprostone (prostaglandin E2) for cervical ripening and induction of
labor in a community hospital. Am J Obstet Gynecol 1999;180:1551–1559
American College of Obstetricians and Gynecologists. Induction of labor
with misoprostol. ACOG Committee Opinion 228. Washington, DC: ACOG,
1999
American College of Obstetricians and Gynecologists. Induction of
labor. ACOG Practice Bulletin 10. Washington, DC: ACOG, 1999
El-Refaey H, O'Brien P, Morafa W, Walder J, Rodeck C. Use of oral
misoprostol in the prevention of postpartum haemorrhage. Br J Obstet
Gynaecol 1997;104:336–339
O'Brien P, El-Refaey H, Gordon A, Geary M, Rodeck CH. Rectally
administered misoprostol for the treatment of postpartum hemorrhage
unresponsive to oxytocin and ergometrine: a descriptive study. Obstet
Gynecol 1998; 92:212–214
Bamigboye AA, Hofmeyr GJ, Merrell DA. Rectal misoprostol in the
prevention of postpartum hemorrhage: a placebo-controlled trial. Am J
Obstet Gynecol 1998;179: 1043–1046
Surbek DV, Fehr PM, Hosli I, Holzgreve W. Oral misoprostol for third
stage of labor: a randomized placebo-controlled trial. Obstet Gynecol
1999;94:255–258
Hofmeyr GJ, Nikodem VC, de Jager M, Gelbart BR. A randomised placebo
controlled trial of oral misoprostol in the third stage of labour. Br J
Obstet Gynaecol 1998;105:971–975
Bamigboye AA, Merrell DA, Hofmeyr GJ, Mitchell R. Randomized comparison
of rectal misoprostol with Syntometrine for management of third stage of
labor. Acta Obstet Gynecol Scand 1998;77:178–181
At Fri, 12 May 2006, GA12L@aol.com wrote:
>
>I'm sorry, but I don't understand why Cytotec is used to induce labour.
>Pharmacia Limited who market Cytotec here clearly state that
>
>"Cytotec is contraindicated in pregnant women and in women planning a
>pregnancy as it increases uterine tone and contractions in pregnancy which may
>cause partial or complete expulsion of the products of conception. Use in
>pregnancy has been associated with birth defects."
>
>Cytotec is indicated for the healing of duodenal ulcer and gastric ulcer
>including those induced by nonsteroidal anti-inflammatory drugs (NSAID) in
>arthritic patients at risk, whilst continuing their NSAID therapy. In addition,
>Cytotec can be used for the prophylaxis of NSAID-induced ulcers. It says nothing
> about using it to induce labour in fact Pharmacia says that when used in
>pre-menopausal women they should ensure that they have adequate contraception.
>The Summary of Product Characteristics (SPC) clearly says in the section
>Undesirable effects
>"A number of side effects have been reported in clinical studies or in the
>literature following use of misoprostol for non-approved indications. These
>include abnormal uterine contractions, uterine haemorrhage, retained placenta,
>amniotic fluid embolism, incomplete abortion and premature birth."
>So using Cytoec for inducing labour is a) using it for a non-approved
>indication and b) it CAN cause AFE.
>So why is it used to induce labour? Sorry, I don't understand but I'm sure
>one of you will enlighten me!
>Gail
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“ The greatest obstacle to knowledge is not ignorance,
it is the illusion of knowledge.” Daniel J. Boorstin - Historian
