The Alleged Evils of Cytotec

Studies of Cytotec (misoprostol) over the last several decades have overstated the danger of using this medication for cervical ripening without differentiating its use for cervical ripening as opposed to induction. Today “evidence-based medicine” is considered to be the gold standard. Everybody uses the term. Often, a number multiplied by another number gives a third number which is considered “evidenced- based.” For example, a recent PubMed article reported on a study to try to determine the U.S. number of iatrogenic deaths (deaths caused by medical examinations or treatments).

This study collected data from 25 hospitals in Pennsylvania using the Medication Error Reporting (MEDMARX) system. In this PubMed article, we are told that “‘medical errors account for 251,000 deaths annually, making medical errors the third leading cause of death.”

Since this study was not done on all the hospitals in Pennsylvania, I’m not certain how the authors could even begin to extrapolate their numbers from 25 hospitals to represent all the hospitals in Pennsylvania, let all of the hospitals in the U.S. So, this “evidence-based” study cannot hope to represent the actual rates across Pennsylvania, much less the U.S. Yet these conclusions are graced with the labels “studies show” and the current buzzword, “evidence-based.”

On the other hand, anyone reporting one incidence of an occurrence is chastised for putting any credence in anecdotal evidence, even if that incidence is repeated 1000 or 2000 times. This gets us back to the topic of Cytotec and the often reported evils of this medication. The research studies of Cytotec do not differentiate between the use of a small dose of Cytotec for cervical ripening and the use of multiple large doses of Cytotec for induction.

The generic term for Cytotec is misoprostol, a synthetic prostaglandin E1 analog that is used off-label for a variety of indications in the practice of obstetrics and gynecology, including medical management of miscarriage, induction of labor, cervical ripening, and the treatment of postpartum hemorrhage. A PubMed article reports that due to its wide-ranging applications in reproductive health, misoprostol is on the World Health Organization (WHO) Model List of Essential Medicines.

The broad class of prostaglandins have been used for 50 years the for cervical ripening and induction of labor. Initially, the use of prostaglandins for cervical ripening and induction were off-label. Because these uses were off-label, the cost was low. I remember paying about five dollars for one application. Drug companies often don’t go through the expense of testing and getting approval for an “off-label” use of a medication if the pharmaceutical company doesn’t see an opportunity to recoup the costs of the government approval process. When certain prostaglandins became “on-label,” their price increased to $250 per application. Many people misunderstand the use of “off-label.” These medications are approved for human use and are safe, effective, readily available, and often inexpensive.

After having used many different kinds of prostaglandins, eventually I decided on the use of Cytotec. Naturally, I read the studies in which nurses in labor and delivery inserted 50 to 200 micrograms into a patient’s vagina every two hours until labor started. Using these large amounts of Cytotec were shown to be dangerous with a high risk of uterine rupture. These high dosages are now banned in many settings, and with good reason if the intent is induction.

I developed a protocol for the use of a single small dose of misoprostol given in my office for what can be called cervical ripening. I could see what happened to the patients who received misoprostol vaginally. I quickly learned that even 50 micrograms one time was excessive. I found that a single dose of 25 micrograms was sufficient to soften the cervix for 95 percent of my patients. I also learned that if one 25 microgram dose of misoprostol did not initiate cervical ripening, those patients were not ready for labor and delivery and I had them return to my office in a few days.

I watched my patients carefully in my office monitoring the baby’s and mother’s contractions for 4 to 6 hours. Initially the contractions would be small, frequent, and short. Mothers perceived these pains as menstrual cramps, but they were important for cervical ripening.

After 4 to 6 hours, I sent the mothers home for a few hours. Most of them returned to the hospital in a few hours 5, 6 or 7 cm dilated with a thin, soft, favorable cervix. With an amniotomy, most of these patients delivered within an hour or two. There were no complications. No babies were delivered outside of the hospital. No mothers had ruptured uteri. No mothers had blood transfusions. This method of cervical ripening led to what what was very similar to natural labor, and most of the mothers did not need an epidural.

To my knowledge, there are no research studies looking at how Cytotec can be safely used in a 25 microgram dose for cervical ripening.

We don’t need one more article talking about the evils of Cytotec. We need research studies of the use of a 25 microgram dose of Cytotec for cervical ripening.

Paracelsus said it well.

“What is there that is not poison? All things are poison, and nothing is without poison.
Solely the dose determines that a thing is not a poison.”

So, according to Paracelsus, the poison is in the dosing. With the small dose or Cytotec I used for cervical ripening, I never saw hyperstimulation or fetal distress. The key to successful management of cervical ripening is a one-time 25 microgram vaginal dose of misoprostol. I’d like to see some evidence-based studies of a small dose of Cytotec to initiate labor.