Fetal Heart Rate Abnormalities Higher With Cytotec Inductions

OB/GYN News, July 1, 2001 by Heidi Splete

SAN DIEGO -- Cytotec was more effective for cervical ripening and labor induction with an unfavorable cervix than were two forms of dinoprostone, but it was associated with a higher incidence of fetal heart tracing abnormalities.

In a prospective, randomized study of 111 obstetric patients, those who received Cytotec (misoprostol) had a quicker induction of labor, averaging 24 hours from the administration of the drug until delivery, compared with 30 hours in patients who received either Cervidil or Prepidil, Dr. Patrick S. Ramsey said at the annual meeting of the Society for Obstetric Anesthesia and Perinatology.

Nevertheless, Cytotec was associated with a significantly higher incidence of fetal heart tracing abnormalities and contraction abnormalities (50%), compared with Cervidil (14%) and Prepidil (11%), said Dr. Ramsey, who conducted the study while at the Mayo Clinic in Rochester, Minn.

Cytotec is approved by the Food and Drug Administration solely for the prevention and treatment of peptic ulcers. Nevertheless, it is frequently used off label for cervical ripening and labor induction in pregnant women.

Searle, which manufactures Cytotec, sent a letter to health care providers last year reminding them not to use the drug in pregnancy.

In response, the American College of Obstetricians and Gynecologists issued a statement that Cytotec, when used appropriately, is a safe and effective agent for cervical ripening and labor induction as well as for treating serious postpartum hemorrhage.

Cervidil and Prepidil are both indicated for cervical ripening.

In the current study, which is part of an ongoing, randomized trial comparing cervical ripening products, the women were randomized to receive either 50 [micro]g of Cytotec every 6 hours for a maximum of two doses, 0.5 mg of Prepidil every 6 hours for two doses, or 10 mg of Cervidil for 12 hours.

There was no significant difference among the three groups in maternal age, gestational age, epidural use, or cesarean rate, according to Dr. Ramsey, who is now with the University of Alabama, Birmingham.

The investigators studied the overall incidence of fetal heart tracing and contraction abnormalities during the first 24 hours after administration of the drugs.

The incidence of tracing abnormalities within 6 hours of the initial dose was significantly higher in the Cytotec group (34%), compared with the Cervidil (2.9%) and Prepidil (3.7%) groups.

Tracing abnormalities induded hypertonus, defined as a single uterine contraction lasting more than 2 minutes, and tachysystole, defined as more than six uterine contractions in a 10-minute window for two consecutive 10-minute windows.

In addition, Cytotec was associated with a higher mean number of adverse events (3.5 per patient), compared with Cervidil (0.4 per patient) and Prepidil (0.2 per patient).

There was no significant difference between groups in the incidence of hyperstimulation syndrome, which was defined as the presence of either hypertonus or tachysystole with fetal bradycardia, tachycardia, and heart rate decelerations, Dr. Ramsay reported.

Because of the interest in outpatient use of Cytotec for cervical ripening, the investigators reviewed the average time to the first fetal heart tracing abnormality.

This time was significantly shorter in patients receiving Cytotec--approximately 6 hours--compared with 10 hours for the Cervidil patients and 12 hours for the Prepidil patients.

"The abnormalities in the fetal heart tracings occurred as little as 3 hours after Cytotec administration, raising important concerns about potential outpatient use of this agent," Dr. Ramsey noted during the meeting.