Consortium for the Evidence

Misoprostol , given as a 1/4 of a small tablet placed in the vagina.
Misoprostol is an ulcer drug that is contra-indicated in pregnant women, not approved for induction of labor, associated with increased uterine rupture and maternal/fetal/neonatal death.

Uterine hyperstimulation / tetonic contractions -- less than 2 1/2 minutes between contractions or lasting longer than 75 seconds, can occur up to 12 hours later;

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From: DMECNM@aol.com
Date: Wed, 3 Feb 1999
To: Midwives@lists.alaska.net
Subject: Amniotoic Fluid Embolism (AFE

The June 1999 issue of the American Journal of Obstetrics and Gynecology published the article "Uterine rupture associated with the use of misoprostol in the gravid patient with a previous cesarean section." The data in this article are truly frightening. "Uterine rupture occurred in 5 of 89 patients with previous cesarean delivery who had labor induced with misoprostol. The uterine rupture rate for patients attempting vaginal birth after cesarean was significantly higher in those who received misoprostol, 5.6 percent, than in those who did not, 0.2 percent or 1 in 423, p=0.0001)." Furthermore, a medical records review turned up several more cases of uterine rupture associated with using Cytotec with VBAC not included in their calculations.

Be clear on what this says. Over five percent of women given Cytotec for VBAC had a ruptured uterus, a 28-fold increase over those who did not have Cytotec induction for VBAC. This is a truly shocking rate of uterine rupture. And one of the five women with uterine rupture ended up with a dead baby as a result of the rupture. Just in case you think this paper reports an aberration, the same issue of this journal has a second paper in which three of eighty-one women receiving Cytotec for a VBAC had uterine rupture--a still shocking rate of 3.7 percent. And one of the three babies died in the NICU after the rupture. Both these papers were retrospective which means that none of the women given Cytotec were part of a research project. Thus, none had received the protection of research subjects, including information on the experimental nature of the drug given to them.

So in these two papers, of 170 women given Cytotec for induction with VBAC, eight have lost their uterus and two lost a baby as well. It is my educated guess that to this day none of them has been told that they were given a drug for a purpose not approved by the FDA nor has been told their case is described in published papers saying this drug should not be used in this way. These women and babies paid a very big price because their practitioners were willing to use a very powerful drug before it has been approved by the FDA for this purpose and before it was adequately evaluated by prospective, controlled research.

Marsden Wagner MD, MSPH

Subject: Cytotec warning from Searle Pharmaceuticals

Please forward this warning letter to MDs, CNMs, MWs, RNs on your address books.

> August 23, 2000

> Re:Cytotec? (misoprostol)

> IMPORTANT DRUG WARNING CONCERNING UNAPPROVED USE OF INTRAVAGINAL OR ORAL MISOPROSTOL IN PREGNANT WOMEN FOR INDUCTION OF LABOR OR ABORTION

> Dear Health Care Provider:

> The purpose of this letter is to remind you that Cytotec administration by any route is contraindicated in women who are pregnant because it can cause abortion. Cytotec is not approved for the induction of labor or abortion.

> Cytotec is indicated for the prevention of NSAID (nonsteroidal anti-inflammatory drugs, including aspirin)-induced gastric ulcers in

> patients at high risk of complications from gastric ulcer, e.g., the elderly and patients with concomitant debilitating disease, as well as patients at high risk of developing gastric ulceration, such as patients with a history of ulcer.

> The uterotonic effect of Cytotec is an inherent property of prostaglandin E1(PGE1), of which Cytotec is stable, orally active,

> synthetic analog. Searle has become aware of some instances where Cytotec, outside of its approved indication, was used as a cervical ripening agent prior to termination of pregnancy, or for induction of labor, in spite of the specific contraindications to its use during pregnancy.

> Serious adverse events reported following off-label use of Cytotec in pregnant women include maternal or fetal death; uterine

> hyperstimulation, rupture or perforation requiring uterine surgical repair, hysterectomy or salpingo-oophorectomy; amniotic fluid embolism; severe vaginal bleeding, retained placenta, shock, fetal bradycardia and pelvic pain.

> Searle has not conducted research concerning the use of Cytotec for cervical ripening prior to termination of pregnancy or for induction of labor, nor does Searle intend to study or support these uses. Therefore, Searle is unable to provide complete risk information for Cytotec when it is used for such purposes. 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.

> Searle promotes the use of Cytotec only for its approved indication.

> Please read the enclosed updated complete Prescribing Information for Cytotec.

> Further information may be obtained by calling 1-800-323-4204.

> Michael Cullen, MD

> Medical Director, U.S.

> Searle

Letter / Petition on Cytotec to Acting Commissioner of the Food and Drug Administration