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Update on Spin Doctoring Misoprostol (Cytotec): Unsafe at Any Dose

Last August, I argued against ACOG’s current position on inducing labor with misoprostol, which is that misoprostol is safe “when used appropriately” (p. 387), by which ACOG means provided it is used in doses no greater than 50 micrograms in women with an unscarred uterus. In March, I started work on the induction chapter for the new edition of Obstetric Myths Versus Research Realities, and I decided to see if I could find evidence that ACOG’s confidence was misplaced. I looked for reports of misoprostol catastrophes occurring in U.S. hospitals in women with unscarred uteruses who received no more than 50 microgram doses of misoprostol. I found 11 cases fitting my criteria. Two were single case reports: a uterine rupture leading to hysterectomy in a woman induced solely with two 25 microgram vaginal doses of misoprostol, and a uterine rupture leading to stillbirth and hysterectomy in a woman induced solely with one 25 microgram vaginal dose. The other nine were reported in a case series of severe adverse events following misoprostol induction vaginally or, in one case, orally. All nine women experienced uterine hyperstimulation, which in seven cases was reported as accompanied by severely abnormal fetal heart rate, meconium, or both. The nine cases of hyperstimulation resulted in a total of two cases of uterine rupture, five cases of permanent fetal neurologic injury, two perinatal deaths, and three maternal deaths. One woman with uterine rupture experienced disseminated intravascular coagulation, a life-threatening consequence of severe hemorrhage, and three women had diagnoses of amniotic fluid embolism (AFE). The AFE cases resulted in a maternal death, a maternal death and a brain injured child, and a maternal and perinatal death among the mother-baby pairs. We probably have a twelfth case in comment #17 to the original blog post, but not enough information is given to be sure. (Maddy Oden also posted a comment, but Tatia Oden French’s case is the third of the three AFE cases reported in the case series, a case, by the way, in which Maddy tells me that the coroner’s report mentions AFE but lists the cause of maternal death as “natural causes: cardiac arrest.”)

We’re not done yet. I also ran across a study comparing 95 pre-eclamptic women undergoing pre-induction cervical ripening with vaginal misoprostol with 108 women having ripening with prostaglandin E2. Among women receiving misoprostol, 18% had cesareans for fetal heart rate abnormalities, A.K.A. fetal distress, versus 8% of those having prostaglandin E2, and 14% having misoprostol experienced placental abruption (the placenta detaches partially or completely before delivery) versus 2% receiving prostaglandin E2. So it isn’t just women with cesarean scars who are at especially high risk with misoprostol inductions but women with severe hypertension as well.

I don’t know about you, but if there were a compelling medical reason why I needed labor induced—and most inductions do not fall in this category—and the situation was, moreover, of such concern that induction could not wait for cervical readiness to labor, I would insist on using some means other than misoprostol.

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  1. avatar
    Laurie
    August 4th, 2010 at 03:37 | #1

    As a vbac mom, the dr. suggested trying cytotec if I do not want to try pitocin, as I am usually overdue with healthy babies. As an informed doula and proactive mom, I was way over stimulated by a very low dose of pitocin during my first vbac. I have every contraindication for use of cytotec and pitocin, and it is still being offered. If I were not informed they would probably just use it. And insurance companies are now being questioned on their ban of vbacs-I am currenty under review for our local hospital. The hospital seems pretty excited about this….

  2. August 5th, 2010 at 01:16 | #2

    Good Lord! The American Congress of Obstetricians and Gynecologists, the U.S. ob/gyn’s professional organization, is not known for publishing anything that would cramp the style of their members, but even they have a Committee Opinion going back to 1999 recommending against its use in women with previous cesareans because of the danger of scar rupture. Were I you, I wouldn’t let this doctor near me.

  3. August 5th, 2010 at 10:20 | #3

    Given that the majority of the research was done by Searle Pharmaceuticals (the original manufacturer), starting in the 80′s, how would a couple of case reports or tiny studies matter? Isn’t that just publication bias?

    And if you are inducing for a reason, like pre-eclampsia, and the alternative method doesn’t work as well, don’t you get problems, much more serious problems, related to that?

  4. August 7th, 2010 at 13:01 | #4

    I’m not exactly sure what you are referring to, but Searle has NEVER conducted research into misoprostol’s use as an obstetric agent, and, as my blog post makes clear, other agents are just as effective (prostaglandin E2 results in identical cesarean rates) while carrying a lower risk profile. Specifically, with respect to pre-eclampsia, as I also made clear in my blog post, misoprostol is MUCH more dangerous than prostaglandin E2.

  5. August 10th, 2010 at 06:35 | #5

    “I’m not exactly sure what you are referring to, but Searle has NEVER conducted research into misoprostol’s use as an obstetric agent”

    This is completely ridiculous. Searle and its successors have about 20 re-lablings of the drug. In every single blasted one of them, as in the original research, its abortifacient/obstetrical properties must be addressed.

    Your extremely limited knowledge and unscientific skills don’t allow you to know about these and access them. This is obvious plain-as-the-nose on-your-face level stuff to anyone in pharma or medicine. And you don’t even know it exists!!!

    The only way anyone knows cytotec can do these things is because it was found to cause spontaneous abortions in Phase III. Searle originally explored marketing this drug as the first abortion pill, but backed away due to threats of boycott or vandelism by anti-abortion groups. Its induction properties were also investigated at the same time, which is where the OB community got the idea from!!!!!

    They have to file reports. They have to keep track of adverse effects and other things, whether they are in label or not.

    Searle and successors have been able to have their cake and it too by not seeking FDA approval. They avoided the anti-abortion anger and then any product liability related to for OB. Nevertheless, it is widely used for both. I mean really, who uses this drug for ulcers anymore? It would have been relegated to the generic heap a long time ago, if that was the case. They have also been accused from time to time for covertly marketing it as an OB drug. Its acquistion of Roche’s women’s health product line in the 90′s was partly motivated by the need to have an excuse for it to be doing things with OBs!!!

    They have been researching this “side effect” for over 25 years.

    If you disagree with the blatantly obvious facts presented here, what is your story as to how this drug came to be so widely used for these off-label uses? I can’t wait to hear the laughably implausiable “old midwives tale”. The OBs that, you know, just don’t follow the evidence, just grabbed any ol’ drug off the formulary shelf and gave it to a mom in labor…….

    Bottom line is you don’t know what you are talking about because you know so little about medicine, research, and pharma. You only access data that unscientific amateurs can find through Google while watching Grey’s Anatomy.

    Obviously, your comments demonstrate you know absolutely nothing about the pharmaceutical industry and its research and regulation. Your comments, like most of this forum are amateurish attempts to present your agenda, beliefs and professional self-interests as science.

  6. avatar
    b
    August 12th, 2010 at 10:43 | #6

    Oh, yeah, right Searle NEVER did research on cytotec for obstetrics. Geez.

    http://www.nytimes.com/1988/10/29/world/us-may-allow-anti-ulcer-drug-tied-to-abortion.html

    “Ms. Bruno said the drug’s abortion-inducing effects were tested only to assess the dangers to patients taking it for other reasons.”

    “To test the drug’s hazards in pregnancy, Ms. Bruno said, Searle gave Cytotec to a small group of women in their first trimester of pregnancy who planned on having abortions. The tests, conducted in West Germany in the early 1980′s, showed that the drug caused ”uterine expulsion and bleeding,” Ms. Bruno said.”

    “Dr. Richard Glasow, another official of National Right to Life, said the group had not yet decided what actions to take against Searle, but that a boycott of Searle products, including Nutrasweet, was a possiblity.”

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