Mifepristone label gets new safety information

The manufacturer of the abortion pill mifepristone (Mifeprex, Danco Laboratories; New York City) has revised the safety information for the drug’s label and issued a letter to health care providers in light of five deaths from serious bacterial infection and sepsis following use of the medication abortion regimen.

According to Danco, there have been more than 460,000 estimated uses of Mifeprex from September 2000 through June 2005. During that time, the company says it has received reports of five deaths following treatment with Mifeprex and misoprostol. One case occurred in 2001 during a Canadian clinical trial; the other four cases of septic deaths came from California during September 2003 to June 2005. Scientists have identified the bacteria in two of the cases as Clostridium sordellii, an anaerobic, gram-positive bacteria; the others cases are under investigation by the Food and Drug Administration (FDA), along with the Centers for Disease Control and Prevention (CDC), state and local health departments, and Danco Laboratories.

The company is working closely with FDA to alert health care providers. It has issued a "Dear Doctor Letter" to all Mifeprex providers and emergency department directors, reports Cynthia Summers, DrPH, Danco’s director of marketing and public affairs.

The FDA is working with the manufacturers of Mifeprex and misoprostol tablets to conduct special tests to ensure there was no contamination of either product with Clostridium sordellii. The investigations are ongoing, according to the agency.

In its alert to health care professionals, the FDA advises clinicians to tell patients to contact it if they develop weakness, nausea, vomiting or diarrhea, with or without abdominal pain and fever, more than 24 hours after taking misoprostol. These symptoms, even in the absence of fever, may indicate sepsis, the agency notes. Patients also should contact health care providers immediately if they have heavy bleeding (defined as soaking through two thick full-size sanitary pads per hour for two consecutive hours), or a fever of 100.4°F or higher that lasts for more than four hours.

In November 2004, the FDA announced the addition of information concerning rare cases of serious and sometimes fatal infections to the warnings section of the Mifeprex label.

Although the oral provision of misoprostol is the FDA-approved regimen, all four deaths in California involved intravaginal administration of misoprostol. A causal relationship between intravaginal administration of misoprostol and an increased risk of infection or death has not been established, states Summers. The company is closely working with the FDA, health care providers, and other medical experts to understand the circumstances surrounding these events, she adds.

Physicians are free to prescribe FDA-approved drugs as they wish. Summers points out. There are many studies published in the peer-reviewed medical literature that discuss various regimens of Mifeprex and misoprostol, and many physicians may be basing their regimens on that literature, she notes.

The FDA-approved regimen for medication abortion using mifepristone and misoprostol is:

  • Day One: Three tablets of 200 mg Mifeprex orally at once.
  • Day Two: Two tablets of 200 mcg misoprostol orally at once.
  • Day 14: The patient must return to confirm that a complete termination has occurred. "Danco uses only the FDA-approved regimen in its labeling and promotional materials and does not promote any other regimens," Summers explains.

Should women undergoing medication abortion receive antibiotics to prevent fatal infections? The FDA says it does not have sufficient information to recommend such use of preventive antibiotics.1

Fatal sepsis very rare

Reports of fatal sepsis in women undergoing medical abortion are very rare: 1 in 100,000, the agency reports.1

"Preventive antibiotic use carries its own risk of serious adverse events such as severe or fatal allergic reactions," the agency notes. "Also, preventive use of antibiotics can stimulate the growth of superbugs,’ bacteria resistant to everyday antibiotics."

Planned Parenthood Federation of America (PPFA), based in New York City, is revising its patient information to reflect the new information, reports Scott Spear, MD, chairman of PPFA’s National Medical Committee.

Remind patients that medication abortion (also known as medical abortion) is an evidence-based regimen, it appears to be safe, and that the infections that have been found do not appear causally related to mifepristone or misoprostol, he says.

Anita Nelson, MD, professor in the obstetrics and gynecology department at the University of California in Los Angeles (UCLA) and medical director of the women's health care programs at Harbor-UCLA Medical Center in Torrance, says, "The change in the warning for mifepristone to mention that generalized malaise even in the absence of fever should prompt the patient to seek evaluation seems prudent, as long as it is understood that medical abortions is a safe and effective procedure, with fewer risks than pregnancy."

Reference

  1. Food and Drug Administration (FDA). Questions and Answers on Mifeprex (mifepristone). Accessed at: www.fda.gov.

Resource

Visit the Mifeprex web site, www.earlyoptionpill.com, to download files of the health care provider letter, as well as the revised prescribing information, medication guide, and patient agreement. Information also is available in Spanish. At the opening page, scroll down to "Information for Providers." Click on the prescribing information, medication guide and patient agreement listed under it. The Spanish information is listed under the "En Español — Informacion Para Los Pacientes" section.