Mifepristone/Misoprostol Abortion: FDA Rejects Safeguards Used in China, France, Sweden and the United KingdomMifepristone/Misoprostol Abortion: FDA Rejects Safeguards Used in China, France, Sweden and the United Kingdom
Fact Sheet: FDA rejects safeguards used in other countries
Dangers inherent in method evident in precautions used in France: The Food and Drug Administration based its 1996 finding that drug-induced abortion using mifepristone and misoprostol ("M/M") was "safe and effective" on results involving a subgroup of women (1,681) in French trials. M/M abortions in France are performed at government-operated hospitals and clinics, typically with or adjacent to emergency room facilities. Women are screened for numerous medical conditions that rule out use of the two drugs. Ultrasound is used to determine gestational age and to rule out tubal pregnancy.
After women are given prostaglandin (e.g., misoprostol), they are monitored on site for approximately four hours so that allergic reactions, cardiopulmonary "events," hemorrhaging and the like can be treated promptly before they become life-threatening. A 1990 directive jointly signed by the French Republic's Director General of Health, Director of Hospitals and Director of Pharmacy and Medication, states that whenever prostaglandins are given "in association with RU 486" the "following technical conditions ... are indispensable and are to be followed: ... b) The doctor must ensure that diagnostic instruments and machines are close by, such as electrocardiogram equipment and particularly resuscitative cardiopulmonary equipment (including nitrous oxide and injectable calcium antagonists and a fibrillator). ... c) [C]linical observations and blood-pressure readings every half hour are indispensable for several hours following the administration of these drugs. d) Whenever there is chest pain, an electrocardiogram should be taken on the suspicion of rhythm troubles and in case of significant lowering of blood pressure" (April 12, 1990 letter from the French Republic, Department of Solidarity, Health and Social Protection, reprinted in Child & Family 21:102-103, 1990).
In Sweden, women are "supervised by the midwife for 4 to 6 hours at the outpatient clinic" (M. Bygdeman et al., "Medical Termination of Early Pregnancy: The Swedish Experience," Journal of the American Medical Women's Assn. ["JAMWA"], Supplement 2000, 55:3; 195, 196).
In China "the emphasis on close medical supervision is well accepted. ... It is stressed that misoprostol should be taken in the clinic and followed by several hours of observation" (S. Wu, "Medical Abortion in China," JAMWA, Supplement 2000 at 197, 199). The long observation is one reason staffs in some large hospitals in China are growing reluctant to prescribe the drug combination: "The number of medical abortions has decreased recently in some of the large hospitals. The staffs were too busy to handle the procedure (more counseling, more visits, and observation), and they also have to manage the referred cases with serious side effects and complications" (Id. at 199).
Searle, which manufactures misoprostol under the brand name Cytotec, has consistently opposed the use of Cytotec for labor induction and for abortion. An August 23, 2000 letter from Searle, posted on the FDA's website (http://www.fda.gov/medwatch/safety/2000/cytote.htm), reiterates its opposition to these off-label uses and lists "serious adverse events" that have been reported: "maternal and fetal death; uterine hyperstimulation, rupture or perforation requiring uterine surgical repair, hysterectomy or salpingo-oophorectomy; amniotic fluid embolism; severe vaginal bleeding, retained placenta, shock, fetal bradycardia and pelvic pain." The Cytotec patent expired in July 2000.
FDA Proposed Modest Precautions: The private, less regulated health care system of the U.S. cannot offer women taking M/M the same level of safety unless the drugs are given, and women monitored, in settings like hospital out-patient facilities. It was widely reported in June 2000 that, nodding to these safety concerns, the FDA proposed making mifepristone available only to licensed physicians trained in surgical abortion, trained and certified in ultrasonography and in the use of M/M under an FDA-approved curriculum. Prescribing doctors also would need to maintain admitting privileges at a hospital no more than one hour from their main office. (See July 24, 2000 Release, American College of Obstetricians and Gynecologists.)
Inexplicably, the FDA-proposed protocol did not mandate on-site observation after taking misoprostol, although this protocol is followed in France, China, Sweden, the United Kingdom and is the common practice virtually everywhere the drug combination is used.
Final Approval Ignores Safety Concerns: Between June and September 2000, something caused the FDA to relax even these modest precautions. Under the final approval issued September 28, 2000, prescribing doctors need only sign an agreement with a distributor of mifepristone that he/she can do the following: assess pregnancy duration accurately; diagnose tubal pregnancy; provide surgical intervention OR have a referral arrangement with an abortion provider; assure patients access to medical facilities equipped to provide blood transfusions and resuscitation. Additionally, doctors must see patients at 14 days and report all on-going pregnancies, serious adverse events, hospitalizations and transfusions. (Mifeprex Prescriber's Agreement).
Bleeding: In U.S. trials conducted by Population Council ("PC"), 9% of women reported bleeding after 30 days and 1% were still bleeding after 60 days. "Excessive bleeding necessitated blood transfusions in four women and accounted for 25 of 27 hospitalizations (including [ER] visits), 56 of 59 surgical interventions, and 22 of 49 administrations of [IV] fluid" (I.M.Spitz, et al., "Early Pregnancy Termination with Mifepristone and Misoprostol in the United States," The New England Journal of Medicine, April 30, 1998, 338:18, 1241-47, hereinafter "NEJM"). In a Columbia University study, 20% of women bled or spotted for 5 to 6 weeks (A. Davis et al., "Bleeding Patterns After Early Abortion with Mifepristone and Misoprostol or Manual Vacuum Aspiration," JAMWA, Supplement 2000, 141, 143).
Dr. Mark Louviere treated a Waterloo, Iowa woman who had participated in Population Council trials. Two weeks after her M/M abortion, she was taken to a hospital emergency room where Dr. Louviere found her "in obvious shock" having "lost between one-half to two-thirds of her blood volume. ... It was my clinical opinion that she would die soon. ... Without even doing the routine preparation we normally do for surgery, I realized that I had to take her immediately to surgery to save her life" (FDA Reproductive Health Drugs Advisory Committee, Hearing Transcript, July 19, 1996 at 224). The next day, he advised Planned Parenthood of Greater Iowa which in turn informed Population Council. Both organizations, however, reported "no complications," and "no adverse events ... during the course of this trial" (Id. at 19-20).
Two patients in Des Moines, Iowa trials told a TIME magazine journalist that their bleeding was "like turning a jug of water upside down" and "like a faucet was turned on. There was a steady stream of blood. I passed a golf ball size blood clot that scared me" (Sachs, "Abortion Pills on Trial," TIME, 12/5/94, p. 45).
Allergic reactions: The FDA warns that M/M abortion is contraindicated in women with known allergies to either drug. (Mifeprex Package Insert ["MPI"]). But how would one know of such an allergy in advance? Dr. Wu Shangchun, with the National Research Institute for Family Planning in Beijing reports: "The common complications of medical [drug-induced] abortion are profuse bleeding and allergy. ... Allergic reactions to mifepristone or misoprostol were not uncommon, manifesting in facial edema, skin rash and itching, numbness of feet and hands, and even a serious case of allergic shock. The potential for such reactions is one reason to keep clients for observation" (Wu, op. cit., at 198).
Infection: Four percent of women in PC's U.S. trials had fever, viral infection and vaginitis associated with the abortion. Ten cases of study-related endometritis (inflammation of uterine lining) also occurred. (NEJM, op cit. at 1244). A recent review of M/M regimens around the world reports on a trial involving 2000 cases (P.W. Ashok et al., "An Effective Regimen for Early Medical Abortion: A Report of 2000 Consecutive Cases," Human Reprod. 1998; 13:2962-2965): "The most common problems reported at follow-up were continued pain, vaginal bleeding, and offensive discharge. Antibiotics were prescribed for 5% of the 1322 women for presumed genital infection" (H. Von Hertzen, "Research on Regimens for Early Medical Abortion," JAMWA, Supplement 2000, 133, 136). A World Health Organization study recommended giving antibiotics to women for six weeks following M/M abortions, finding an infection rate of 29.4% among women who had incomplete abortions. (World Health Organization, "Pregnancy Termination with Mifepristone and Gemeprost: A Multicenter Comparison Between Repeated Doses and a Single Dose of Mifepristone," Fertil. Steril., 56:1, 1990, 32-40).
Failure Rates: Mifepristone alone was effective for only 6% of women in PC's U.S. trials in the 48 hours preceding misoprostol administration. About half of the women studied expelled their embryo within four hours of taking misoprostol, and a total of 69% had completed abortions within 24 hours of taking misoprostol. Many of the remaining 31% faced up to two weeks of pain, nausea and bleeding. Eight percent of women in the PC trials needed surgery, due to incomplete abortions (4.7%), ongoing pregnancies (1%), and medical reasons, usually excessive bleeding (1.6%); an additional 0.6% requested surgery. (NEJM, op. cit., at 1242).
Accuracy in determining gestational age is critical because failure rates increase dramatically after 49 days LMP—17% at 50-56 days and 23% at 57-63 days. (Id. at 1243). Untreated, incomplete abortion can result in infection, sterility and death.
Additional Dangers to Women under Lax Standards Set by FDA: Failure to diagnose an ectopic pregnancy can result in maternal death. (Wu, op cit., 198-199) "Some recent adverse events resulting from undiagnosed ectopic pregnancies have led providers to pay more attention to ultrasound examination. One study found that 84% of providers in Beijing used ultrasound routinely..." (Id. at 197). The FDA has dropped the reported requirement that prescribers be certified in the use of ultrasound.
The nature of abortion practice in the United States is that nine out of ten abortions take place free-standing abortion clinics or in doctors' offices (Alan Guttmacher Institute, Facts in Brief) with minimal government supervision. There are no guarantees that doctors prescribing mifepristone and misoprostol to U.S. women will adequately screen for medical conditions that make use of these drugs dangerous, among which are: adrenal insufficiency; coagulation disorders; use of steroid medications; known allergies to the drugs; liver, respiratory, renal or cardiovascular disease, thromboembolism, hypertension, anemia and insulin-dependent diabetes mellitus. (Source: MPI and NEJM, op. cit.)
Women in the U.S. often do not return to abortion clinics for the required follow-up appointment. Suzanne Poppema, a Seattle abortion provider, has said they are "lucky if 30-40% of patients" return. In PC's U.S. trials, despite stringent counseling standards, 5% of women failed to return for the day 14 checkup. Not only do women with incomplete abortions or hemorrhaging risk death, but those with ongoing pregnancies are also at risk. Eight malformations to children were reported in 71 cases of continuing pregnancy in France, Sweden and the United Kingdom between 1987 and 1998. (Von Hertzen, op. cit. at 136).
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