The Great Cytotec Debate

“Fear of a name increases fear of a thing itself.” Albus Dumbledore

Of course the name the quote above references is Voldemort, the bad guy in the Harry Potter series, but in the birthing world our Voldemort of the moment seems to be Cytotec aka Misoprostil aka Miso.

The similarities between Voldemort and Cytotec end at the fear of the mere mention of the name itself, and in the fact that they’ve both been the catalyst in the deaths of people, either real or imagined so we’ll hold those thoughts and jump into the heart of the Cytotec issue and leave our Harry Potter friends behind.

It’s no great mystery that there is a lot of fear surrounding the use of Cytotec in the birth community today. However I’m often puzzled by assertions and claims made by doulas and other birth advocates when it comes to this issue. There is a lot of outdated information and complete lack of understanding as to not only the use of this drug, but the use of drugs in an off-label situation.

I’d like to start with my opinion of why Misoprostil has wound up with such a bad name. The primary factor in my opinion is that when Misoprostil began to be used for the induction of labor there was no established “safe dose”. There were no randomized controlled trials to establish safety and efficacy and thusly providers across the US were left to try and figure out what worked best. As a result women were given too much, and tragedy occurred. We’ve also learned that the use of prostatglandins in women with a previous cesaeran scar is a huge no no. Cytotec was being given to women with a history of cesarean surgery add in the lack of any established ‘safe dose’ and it was a disaster.

Off label use of drugs is an accepted practice in the medical community. Children who are born with congenital heart defects that require surgery can be given Viagra to help support their hearts.

Magniesum Sulfate when used for premature labor and/or preeclampsia is being used off label.

Off label use in and of itself is NOT bad. But all too often I see “Cytotec is not approved for labor induction, it’s being used OFF LABEL” as some kind of justification as to why it shouldn’t be used. If that’s the case then Mag Sulfate is off the table now too, right?

Another common reference I see made is that Cytotec carries a black box warning against its use in pregnancy and that the manufacturer has said that it shoudln’t be used to induce labor. In August of 2000 Searle did send out a letter the summary of which can be boiled down to:

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.

The above isn’t a statement that it shouldn’t be used for labor induction, it’s a legal move to protect them from lawsuits should it be used and/or misused and a lawsuit ensues.

The current warning against use in pregnancy is stated as such:
WARNINGS. Cytotec should not be taken by pregnant women to reduce the risk of
ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs).

Since the 2000 letter to physicians Pfizer has acquired Searle and the current package inserts state:

Cytotec can induce or augment uterine contractions. Vaginal administration of Cytotec, outside of its
approved indication, has been used as a cervical ripening agent, for the induction of labor and for
treatment of serious postpartum hemorrhage in the presence of uterine atony. A major adverse effect of
the obstetrical use of Cytotec is hyperstimulation of the uterus which may progress to uterine tetany with
marked impairment of uteroplacental blood flow, uterine rupture (requiring surgical repair, hysterectomy,
and/or salpingo-oophorectomy), or amniotic fluid embolism. Pelvic pain, retained placenta, severe
genital bleeding, shock, fetal bradycardia, and fetal and maternal death have been reported.
There may be an increased risk of uterine tachysystole, uterine rupture, meconium passage, meconium
staining of amniotic fluid, and Cesarean delivery due to uterine hyperstimulation with the use of higher
doses of Cytotec; including the manufactured 100 mcg tablet. The risk of uterine rupture increases with
advancing gestational ages and with prior uterine surgery, including Cesarean delivery. Grand multiparity
also appears to be a risk factor for uterine rupture.

All package inserts list possible known side effects. So the citation of the above is common and accepted practice. Has anyone read the package inserts for Mag Sulfate, Pitocin, etc? Same types of disclosures.

In addition to the more recent updates to the package inserts to outline the risks for the now accepted use of Cytotec in obstetrics, randomized controlled trials have been conducted to test and establish efficacy for a Misoprostol Vaginal Insert that will be used for cervical ripening and labor induction.

I have not seen the full study results but my suspicion is that if the results are favorable that we will see the implementation of this product in the years to come.

Having said all of the above, you might wonder where I stand when it comes to Cytotec and its use in obstetrics. My general approach is to avoid the use of “always” and “never” much preferring the middle ground of “It depends.” I’ve had clients participate in the MVI trial I linked above since one of our local hospitals was the study site. I’ve seen Cytotec (as traditionally used with a scored tablet) be effective if not intense, and effective and totally bearable without pain medication among my clients. I’ve seen the same with the MVI. I’ve also seen inductions follow the same paths with Pitocin.

My bottom line is that any drug can be abused and mis-used. In my approach to discussing induction methods with clients I suggest they do their own research. Why are we inducing? Is there a medical reason? What is her Bishop’s Score? What is her personal risk threshold when it comes to the use of induction agents and cesarean?

When talking specifically about Cytotec we discuss it’s history, how it came to be used, why it is considered preferential to some providers, how it’s administered and the possible variances in doses when using a scored tablet, and what viable alternative induction methods are available and their benefits or risks.

Beyond that it’s up to my clients to decide what they feel is the best option for them. I have no desire to sway them in any particular direction because my risk threshold may be different than theirs and I am not the one who will have to live with the outcome of this decision. My personal opinion has no place in the discussion.

At the end of the day we as birthing professionals need to be able to sit down and intelligently discuss the issues surrounding Cytotec. We benefit no one, least of all our clients when we run around like our hair is on fire at the mere mention of the possibility of its use. Using arguments like “Have you read the package insert?” or “It’s not been approved for use in labor.” to argue against its use just make us look silly and unprofessional.

**Disclaimer: This post was not meant to be a comprehensive on Cytotec. The idea for the post came from a few recent discussions I’ve participated in or have been reading in other forums where the repeated arguments against Cytotec was “Off Label” and “Package Insert” as if those two statements could or should stand on their own. My desire is to give clarity to the flaws in those two arguments as I see them. **

2 thoughts on “The Great Cytotec Debate

  1. I always cringe when I hear/read the “off label” argument. I’m looking forward to the MVI trial results and the standardization that will hopefully follow. That will allow our clients to make much better decisions about its use.

  2. Cytotec has now been around for decades. Many many studies have evaluated cytotec. Tell me which inducing medicines, tocolytics, or anti seizure meds are FDA approved.
    Cytotec
    Misoprostol (Cytotec), a synthetic analogue of PGE1, has been extensively investigated for use in cervical ripening and labor induction. Originally marketed as a gastric cytoprotective agent in the prevention of gastric ulcers, it is also an effective, safe, and inexpensive agent for cervical ripening, although it is not FDA-labeled for this purpose.
    The peak concentration and the half-life of misoprostol acid (the active metabolite) are 12 and 21 minutes, respectively. When used for cervical ripening or induction of labor, 25 μg placed in the posterior vaginal fornix should be considered for the initial dose (ACOG, 1999).
    Misoprostol can be repeated every 3–6 hours for up to six doses in 24 hours. The 6-hour interval between dosages has been associated with less uterine tachysystole than the 3-hour interval (ACOG, 1999). Redosing is withheld if the woman has greater than 2 contractions in 10 minutes, achieves adequate cervical ripening (Bishop ≥ 8), enters the active phase of labor, or the FHR is Category II or Category III.
    Uterine rupture is a reported complication with the use of misoprostol and its use is therefore contraindicated for women with a history of prior uterine surgery or cesarean birth (ACOG, 1999).
    If induction or augmentation of labor is required after cervical ripening, some providers use oxytocin. Plasma concentration of misoprostol after vaginal administration attains peak levels in 1–2 hours. While there are no recommendations from ACOG about the safe time interval from last dose of misoprostol to initiation of oxytocin, ACOG recommends, in its letter to the FDA (2000), at least 3–6 hours between doses. A reasonable and safe approach is to delay oxytocin administration for induction or augmentation until at least 4 hours after the last dose of misoprostol (based on assessment of uterine activity and fetal status). (Simpson, 2000).

    Given the current evidence, intravaginal misoprostol tablets appear to be effective in inducing labor in pregnant women who have unfavorable cervices. Misoprostol’s cost compares favorably with other prostaglandins used for cervical ripening or induction regimens—for example, a 100 μg tablet of misoprostol costs between $.36 and $1.20, while PGE2 gel costs $65 to $75 and a PGE2 insert costs $165. Further prospective trials are required to define an optimal dosing regimen for misoprostol. This agent is not recommended for patients with prior uterine surgery.

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