The Food and Drug Administration's announcement that it will strengthen the warning label for the drug RU-486, known by the brand name Mifeprex and often called the French abortion pill, is a case of too little too late.
Three Americans have died (as of Nov 2004) after taking the pill since it was approved, during a heavily politicized process by Congress and the Clinton administration, in September 2000. The new announcement suggests that the FDA still hasn't learned its lesson – and that this drug should be taken off the pharmacy shelves.
The story of how RU-486 got approval is buried in 9,300 pages of documents released by the drug agency to the legal watchdog group Judicial Watch, which filed a Freedom of Information Act suit.
These documents show that the Clinton administration – which had been warned of the drug's potential hazards as far back as 1995 in a citizen petition filed by Americans United for Life – pushed to get RU-486 approved before the 2000 election despite the lack of reliable data demonstrating its safety.
Congress may have been satisfied, but many doctors were not. Some researchers had detailed the dangers of RU-486 – including me, in an article I helped write that appeared in The Annals of Pharmacotherapy in January 2003 – but neither the public nor our elected officials took notice.
Then, last September, an 18-year-old named Holly Patterson died after an RU-486 abortion at a Planned Parenthood clinic in CA. An autopsy found that she died of septic shock caused by endomyometritis, an inflammation of the uterus, "due to therapeutic, drug-induced abortion."
One other American, one Canadian, two Britons and one Swede are also known to have died after taking RU-486. And on Monday, the FDA revealed that a third American woman died last January…this newspaper reported that the agency "has received 676 reports of problems with the drug, including 17 ectopic pregnancies, 72 cases of blood loss so severe that they required transfusions and 7 cases of serious infections."
An RU-486 abortion is not a "little white pill," as its advocates like to say, but actually a two-drug regimen, consisting of 600 milligrams of mifepristone followed, one to two days later, by 400 milligrams of a drug called misoprostol. The first pill starves the developing embryo, the second induces uterine contractions to expel it and other tissue.
Serious dangers can arise if a pregnant woman takes the first pill but fails to take the second, or if she or her clinic miscalculate dates, since the dangers of the regimen substantially increase after 49 days from conception, and the ability to cause a complete abortion significantly decreases.
Infection caused by an incomplete abortion that leaves fetal tissue in the uterus has been linked to two deaths while bleeding caused by an incomplete abortion has been linked to one near-death. In addition, RU-486 may mask symptoms of ectopic pregnancy (linked to one death) or lead to cardiac problems, including a myocardial infarction in a 21-year-old woman three days after an abortion.
So how did such a dangerous drug get approval? Investigations of the records have shown that five standard procedural and scientific requirements to prove safety and effectiveness were circumvented to get RU-486 onto the market quickly.
The most serious was the FDA's approval of the drug solely on the basis of uncontrolled clinical trials, contrary to the agency's standard requirement of two randomized, blinded and controlled tests for new drug applications.
Second, the agency approved the drug using its "accelerated approval regulations," which were created by Congress for drugs with higher risks that are justified only because the drugs are better than current therapies for life-threatening illnesses like AIDS and cancer. Pregnancy, needless to say, isn't an illness, serious or life-threatening.
Third, the agency mandated a previously unapproved use for misoprostol, the second drug in the chemical abortion process, over the objections of its manufacturer, Searle. The company had created and marketed the drug to treat gastric ulcers.
Fourth, the FDA approved RU-486 for use without the safeguards observed in the original clinical tests. For example, the agency did not require those who write prescriptions for RU-486 to order an ultrasound, which is necessary to both date pregnancies (ensuring the 49-day limit) and to rule out ectopic pregnancies, in which the fetus develops outside the uterus.
Because RU-486 cannot end an ectopic pregnancy and in some cases mimics the symptoms of one, it is extremely difficult to diagnosis one after the drug is taken. If untreated, ectopic pregnancy can be fatal.
Last, the agency approved the drug for use on women of any age, yet it had no clinical data on the impact on those under 18. This was contrary to the agency's 1996 written directive to the manufacturer that such data would be required for approval.
Safety has been further undermined since the drug's approval. The FDA has effectively stopped enforcing the 49-day limit by doing nothing about abortion providers who prescribe RU-486 beyond that point.
Some providers even advertise on their Web sites that they administer the drug beyond 49 days.
To insulate themselves if anything goes wrong, some providers require women to sign a patient agreement that authorizes the provider to use misoprostol off label and beyond the 49-day limit.
If RU-486 is dangerous, the skeptics will ask, why are there not more reports of women and girls injured from a drug that 360,000 Americans have taken? In part, I suspect, because the reporting of complications ("adverse events" in medical jargon) to the FDA or other agencies is voluntary, even if the patient dies.
But even the incomplete picture we have shows that the drug is dangerous. How many deaths are acceptable from a drug that is never medically necessary?
Last year Senator Sam Brownback, Republican of Kansas, and Representative (and now Senator-elect) Jim DeMint of South Carolina unsuccessfull
y put forward a bill – with the backing of Holly Patterson's parents – that would have suspended the drug's approval pending further study. They should renew their effort; if the FDA isn't going to look after the safety of American women and girls, Congress must.
Donna J. Harrison, an obstetrician-gynecologist, is chairman of the subcommittee on Mifeprex of the American Association of Pro-Life Obstetricians and Gynecologists. [DONNA J. HARRISON, M.D.; http://www.nytimes.com/2004/11/19/opinion/19harrison.html?pagewanted=all; 19Nov04]
Mifeprex (mifepristone) Information (FDA)
Mifeprex is used, together with another medication called misoprostol, to end an early pregnancy (within 49 days of the start of a woman's last menstrual period). Since its approval in September 2000, the Food and Drug Administration has received reports of serious adverse events, including several deaths, in the United States following medical abortion with mifepristone and misoprostol. Each time FDA receives a report of a serious adverse event or death after medical abortion with these drugs, the agency carefully analyzes the available scientific information to determine whether or not the serious adverse event or death is related to the use of the drugs.
As previously reported by the agency, several of the women who died in the United States died from sepsis (severe illness caused by infection of the bloodstream) after medical abortion with mifepristone and misoprostol. Sepsis is a known risk related to any type of abortion. Most of these women were infected with the same type of bacteria, known as Clostridium sordellii. The symptoms in these cases of infection were not the usual symptoms of sepsis. We do not know whether using mifepristone and misoprostol caused these deaths.
Patients should contact a healthcare practitioner right away if they have taken these medications for medical abortion and develop stomach pain or discomfort, or have weakness, nausea, vomiting or diarrhea with or without fever, more than 24 hours after taking the misoprostol. These symptoms, even without a fever, may indicate sepsis. Patients should make sure their healthcare practitioner knows they are undergoing a medical abortion.
All providers of medical abortion and emergency room healthcare practitioners should investigate the possibility of sepsis in women who are undergoing medical abortion and present with nausea, vomiting, or diarrhea and weakness with or without abdominal pain. These symptoms even without a fever may indicate a hidden infection. Strong consideration should be given to obtaining a complete blood count in these patients. Significant leukocytosis with a marked left shift and hemoconcentration may be indicative of sepsis.
FDA recommends that healthcare practitioners have a high index of suspicion for serious infection and sepsis in patients with this presentation and consider immediately initiating treatment with antibiotics that includes coverage of anaerobic bacteria such as Clostridium sordellii.
FDA does not have sufficient information to recommend the use of prophylactic antibiotics for women having a medical abortion. Reports of fatal sepsis in women undergoing medical abortion are very rare (approximately 1 in 100,000). Prophylactic antibiotic use carries its own risk of serious adverse events such as severe or fatal allergic reactions. Also, prophylactic use of antibiotics can stimulate the growth of “superbugs,” bacteria resistant to everyday antibiotics. Finally, it is not known which antibiotic and regimen (what dose and for how long) will be effective in cases such as the ones that have occurred.
These recommendations are consistent with warnings in the Prescribing Information and information for the patient in the Medication Guide for Mifeprex.
The approved Mifeprex regimen for a medical abortion through 49 day’s pregnancy is:
* Day One: Mifeprex Administration: 3 tablets of 200 mg of Mifeprex orally at once
* Day Three: Misoprostol Administration: 2 tablets of 200 mcg of misoprostol orally at once
* Day 14: Post-Treatment: The patient must return to confirm that a complete termination has occurred. If not, surgical termination is recommended to manage medical abortion treatment failures.
The safety and effectiveness of other Mifeprex dosing regimens, including use of oral misoprostol tablets intravaginally, has not been established by the FDA.
On May 11, 2006, FDA, in conjunction with the Centers for Disease Control and Prevention (CDC) and the National Institute of Allergy and Infectious Diseases (NIAID), conducted a public workshop.
This workshop, entitled “Emerging Clostridial Disease,” discussed the scientific and medical circumstances associated with reports of morbidity and mortality with Clostridium sordellii and Clostridium difficile infections.
Information pertaining to the Emerging Clostridial Disease Public Workshop can be found at: http://www.fda.gov/cder/meeting/clostridia_disease.htm
* Questions and Answers (issued 8/29/2007)
* Mifeprex Label (approved 7/19/2005)
o Medication Guide PDF document
o Patient Agreement PDF document
* Public Workshop on Emerging Clostridial Disease, May 11, 2006
Historical Information: http://www.fda.gov/cder/drug/infopage/mifepristone/mifepristone_historical.htm
[This is historical information only. For current information, please see http://www.fda.gov/cder/drug/infopage/mifepristone/default.htm]
* You should not buy Mifeprex over the Internet because you will bypass important safeguards designed to protect your health (and the health of others).
* Mifeprex has special safety restrictions on how it is distributed to the public. Also, drugs purchased from foreign Internet sources are not the FDA-approved versions of the drugs, and they are not subject to FDA-regulated manufacturing controls or FDA inspection of manufacturing facilities.
To learn more about buying drugs safely, please see
* Buying Prescription Medicines Online: A Consumer Safety Guide.
* FDA strengthens controls, issues consumer alert on importing certain prescription drugs
* FDA Import Alert
Date created: November 15, 2004; Updated August 29, 2007
November 15, 2004
* FDA announces important labeling changes for Mifeprex (mifepristone, also known as RU-486). Mifeprex Info. [http://www.fda.gov/cder/previous_news2004.htm]