General Information / History / Stats / Types

Mifeprex (mifepristone) (RU 486) (1/01)

On September 28, 2000, the United States Food and Drug Administration (FDA) announced the approval of mifepristone, in combination with misoprostol, for early pregnancy termination. This decision received the enthusiastic approval of the American College of Obstetricians and Gynecologists (ACOG).

Mifepristone is also known as RU 486 and is marketed in the United States under the brand name Mifeprex. When the drug was introduced in France, 1/3 of all abortions became RU 486 abortions. If the same acceptance is found in the United States, 400,000 women per year will undergo Mifeprex abortions, making it a an extremely significant health care issue.

The American Association of Pro-Life Obstetricians and Gynecologists (AAPLOG) opposes the destruction of an unborn human being at any stage of development. Therefore, we oppose pharmaceutical abortion with the same vigor that we oppose surgical abortion. However, pharmaceutical abortion has now become a reality of American medical practice, sanctioned by the FDA and ACOG. A stipulation of the FDA’s approval of Mifeprex is that its distribution be restricted to physicians able to meet certain standards, or "qualifications."

The American Association of Pro-Life Obstetricians and Gynecologists believes these qualifications are insufficiently circumscribed to adequately safeguard the health of American women. We therefore make the following statements regarding these qualifications:

The American Association of Pro-Life Obstetricians and Gynecologists believes these qualifications are insufficiently circumscribed to adequately safeguard the health of American women. We therefore make the following statements regarding these qualifications:

FDA Qualification: Physicians providing, or supervising the provision of, Mifeprex must be able to assess the duration of pregnancy accurately.

Comment: Mifeprex is approved only for the termination of intrauterine pregnancy through 49 days' pregnancy, yet this guideline mentions no required standard for pregnancy dating. Relying on the onset of the last menstrual period to determine early gestational age is inadequate for the purpose of early pregnancy termination with mifepristone and misoprostol. According to the American study by Spitz et al,2 complications of mifepristone/misoprostol abortions are doubled if the gestation is 56 to 63 days, rather than 49 days, at the time of treatment. This same dating discrepancy also resulted in a nine-fold increase in the "complication" of ongoing pregnancy. For purposes of distinguishing a 49 day gestation from a 56 or 63 day gestation, the menstrual history and physical examination will often be unreliable. An imprecise estimation of gestational age is not in the best interest of women using mifepristone since complication rates double with only a one to two week dating discrepancy.

Transvaginal sonography is an established standard for dating in early pregnancy. There is almost a doubling of embryonic size between 49 and 56 days gestation. For the safety of the women involved it would have been prudent for the FDA to require sonographic dating for mifepristone abortions. The American College of Obstetricians and Gynecologists also should have insisted on this standard of care.

FDA Qualification: Physicians providing, or supervising the provision of, Mifeprex must be able to diagnose ectopic pregnancies.

Comment: Ectopic pregnancy occurs in 2% of clinically recognized pregnancies in the United States, and is one of the leading causes of maternal mortality in this country. Therefore, it is imperative that it be recognized and treated in a timely fashion. A woman with an ectopic pregnancy who is mistakenly subject to an attempted mifepristone abortion may have an ongoing ectopic pregnancy, as mifepristone does not effectively abort these pregnancies. She will undoubtedly interpret bleeding and pain as consistent with a pharmaceutical abortion, since these are nearly universal effects of mifepristone and misoprostol. This leaves her with the immediate threat of serious harm, or death, if the ectopic pregnancy ruptures.

Ectopic pregnancy is a contraindication to the administration of mifepristone and the only practical and reliable way to assess for ectopic pregnancy in early gestation is with sonography. Any physician prescribing mifepristone and misoprostol to a pregnant woman without first confirming an intrauterine pregnancy by ultrasound is providing suboptimal care, in our view. Women are entitled to this common evaluation in order to minimize their risk of avoidable harm. Yet ACOG has not supported any standard that would require sonographic evaluation before the administration of mifepristone/misoprostol.

FDA Qualification: Physicians providing, or supervising the provision of, Mifeprex must have the ability to provide surgical intervention in cases of incomplete abortion or severe bleeding, or have made plans to provide such care through other qualified physicians, and be able to assure patient access to medical facilities equipped to provide blood transfusions and resuscitation, if necessary.

Comment: Currently, in many communities, it is status quo for providers of surgical abortions at freestanding facilities to abdicate responsibility for complications of their practice. In these communities, women experiencing a complication of an abortion procedure are left on their own to initiate follow-up with another provider or local hospital emergency department. Mifepristone abortions have an emergency dilatation and curettage (D&C) rate of 2% for excessive bleeding.2

FDA Qualification: Physicians providing, or supervising the provision of, Mifeprex must provide each patient with a Medication Guide and must fully explain the procedure to each patient, provide her with a copy of the Medication Guide and Patient Agreement, give her an opportunity to read and discuss both the Medication Guide and the Patient Agreement, obtain her signature on the Patient Agreement and must sign it as well.

Comment: The FDA's RU 486 approval letter indicates that application for the drug was approved under 21 CFR 314 Subpart H.1 Subpart H–Accelerated Approval of New Drugs for Serious or Life Threatening Illness–is FDA policy which was instituted to provide expedited approval of new treatments for acquired immunodeficiency syndrome (AIDS) and other life-threatening diseases. We are not aware of any approved indication that makes mifepristone a candidate treatment for serious or life-threatening illness. Its only approved indication is termination of early pregnancy. This dishonest use of the FDA's protocol to approve Mifeprex slights American women. Drugs approved under this accelerated approval process can still be considered new and experimental, which generally means that manufacturers and sellers of the drug cannot be held strictly liable for injuries sustained from its use. Patients injured by mifepristone may have less legal recourse to a tort action. Yet there is no requirement that women be informed that they are using a medication not subjected to the usual testing requirements of the FDA and which may have unknown risks. Information about this is not included in the Medication Guide provided for patients, or in the Patient Agreement they sign. Nor is it acknowledged in the literature prepared for abort

ion providers. ACOG should insist that women be notified of this unique status of mifepristone as part of appropriate informed consent. Anything less is an abandonment of quality assurance and patient safety in favor of easy access to abortion.

Further, in another unprecedented move, the FDA did not release the name of the Chinese pharmaceutical firm manufacturing the Mifeprex sold in the United States. This is particularly concerning as there have been recent quality control concerns related to other pharmaceuticals imported from this same manufacturer. It is not clear what warranted the withholding of this information from the American public, especially by a federal agency charged with protecting consumers and patients. With these actions the FDA has applied a lower standard for approving and overseeing the safety of this drug compared to other pharmaceuticals. Meanwhile, the American College of Obstetricians and Gynecologists, self-titled "Advocates for women's health in the 21st century," has been silent with regard to these matters.
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The American College of Obstetricians and Gynecologists has been at the forefront of setting standards in reproductive health care for 50 years. Therefore, it is inexplicable to us, as a special interest group of ACOG, that our parent organization would champion the ready availability of mifepristone without simultaneously championing appropriately rigorous standards for the use of this agent. At this critical juncture ACOG appears to have relinquished its role as guardian of the highest standard of care for women by its refusal to explicitly address the numerous safety issues surrounding the use of this method of abortion.

While reiterating our objection to the destruction of unborn human life at any stage of development, and while remaining opposed to both pharmaceutical and surgical abortions, we also recognize the new reality of mifepristone in American life. We urge ACOG to consider the potential harm done to American women if vigorous standards for its use are not developed and promulgated. This would include standards for pregnancy dating, for ruling out the presence of an ectopic gestation, for holding providers responsible for obtaining appropriate consultation and follow-up for their patients, and for ensuring that women are adequately apprised of mifepristone's experimental status and unknown risks. Without the promotion of such standards it will become increasingly clear that "access to abortion" has replaced "protection of women's health" in ACOG's list of priorities.

References:

1  FDA letter to Sandra P. Arnold, Vice President, Corporate Affairs, Population Council. September 28, 2000. This translates to an estimated 8,000 emergency D&Cs per year in the United States. What assurance do women have that complications of these abortions will be handled differently then in current practice? We urge ACOG to advocate a standard of full physician responsibility for obtaining appropriate consultation and follow-up care in abortion practice–a standard common to other arenas of medical care, but frequently not followed in current abortion practice.


2  Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 1998;338:1241-1247.

For more information from AAPLOG on the mechanism of action of Mifeprex, click here.

 

It is essential for a doctor or pregnancy counselor to understand the dangers involved in a mifeprex abortion. This paper will cover l. How Mifeprex works; 2. the Mifeprex program; 3. The usual clinical course; 4. Complications and dangers of the Mifeprex abortion procedure.

How does Mifeprex work?

It is an anti-progesterone that sufficiently disrupts the uterine lining so that the lining will no longer will nourish the placenta. The early
developing child(embryo), deprived of oxygen and nourishment, dies. Misoprostol, given the 3rd day, is a prostaglandin, which causes strong uterine contractions, expelling the now lifeless human enbryo and placenta.

What is the FDA approved Mifeprex program?

The first visit has four steps:
l. learn about the procedure, side effects and risks;
2. sign patient agreement form (including informed consent agreement);
3. pelvic exam (to decide how pregnant the patient is and if she has an ectopic—see below);
4. take the 600 mg Mifeprex pill.

Common side effects include nausea, vomiting, diarrhea (25%), severe cramping (50%), and bleeding (100%). Visit number 2 is 2 days later, when the patient comes in to take misoprostol, which causes strong uterine contractions to expel the products of conception. Visit 3 is at l5 days, to ensure complete abortion has taken place, or to perform a D&C to remove products of conception if complete expulsion has not taken place.

What is the usual clinical course?

Mifeprex 600 mg is taken on day one, and Misoprostol 400 mg is taken on day 3. 3% of patients abort before day 3, 50% of patients abort within 4 hours of taking the misoprostol on day 3, 75% of patients will abort by day 4. The remaining 25% of patients will bleed and cramp over the next 2 weeks, and 2% will have an emergency D&C for heavy bleeding, (0.2% will have a blood transfusion because of excessive bleeding). And 1% will develop an intrauterine infection. By day l5, 92% will have completed their abortion. At this point 1% will have an ongoing pregnancy, and the remaining 5% will require D&C for retained products of conception. All these complications double if the pregnancy is past "49 days" (i.e., 35 days after conception)—except for the ongoing pregnancy rate, which increases by 9 times. And the misoprostol can cause severe deformities in the developing child. Obviously, this procedure is not without significant health risks to both mother and possible surviving child.

Pregnancy Dating

The FDA requires that physicians providing, or supervising the provision of, Mifeprex must be able to assess the duration of pregnancy accurately. But the method of dating is left up to the abortion provider, most of whom will guesstimate. Very accurate dating of pregnancy is essential when using the Mifeprex abortion technique, which is approved only through 7 weeks or "49 days of pregnancy." If the abortion provider is one week over in estimation, as noted above, the complication rates double, and the ongoing pregnancy rate increases ninefold. The major American study cited to document the safety and efficacy of the Mifeprex abortion technique, the Spitz study, used ultrasound (the gold standard for early pregnancy dating) at the initial exam for all of their patients. Yet the FDA standards leave the method of pregnancy dating up to the abortionist. Menstrual history is often confusing, as irregular bleeding can

occur whether the woman is pregnant or not. A doctor who feels he can differentiate a 49 day pregnancy from a 56 day pregnancy by pelvic exam is badly deceiving himself …..and deceiving his patients. Cost constraints and/or lack of conveniently available equipment or provider expertise will eliminate ultrasound dating for many patients. "Guesstimating" the gestational age will be the rule for many abortionists. The safe standard will degenerate to the convenient standard, to the detriment of the patient and the significant increase of her complications.

Ectopic Pregnancy

Ectopic pregnancy occurs in 2% of clinically recognized pregnancies in the United States, and is one of the leading causes of maternal mortality in this country. Therefore, It is imperative that ectopics be recognized and treated in a timely fashion. The FDA requires that physicians providing, or supervising the provision of, Mifeprex must be able to diagnose ectopic pregnancies. But the method of diagnosing ectopic pregnancy is left up to the abortion provider. Doctors know that the only way to exclude ectopic is with ultrasound. But since ultrasound is not required, it will most likely not be used, (due to expense and inconvenience). It is essential to make the ectopic diagnosis before giving mifeprex, since mifeprex does not
effectively abort ectopics. To the patient, (and to the provider), the
bleeding and pain of a mifeprex abortion or a rupturing ectopic will be the identical . . . except that the patient can bleed to death internally from a ruptured ectopic. (According to the FDA report of April, 2002, one woman has already died of this complication.)

The "Lost Patients"

In the largest American study (Spitz study) of early pregnancy termination with mifepristone and misoprostol a rigid clinical protocol was followed,with ample personnel and resources available to follow patients. Even under these ideal circumstances, 5% of the carefully screened participants were "lost to follow up." Practically speaking, this means 5% of the women who had agreed to follow the formal protocol took the mifeprex on day l, took the misoprostol on day 3, and simply "disappeared."

What ever became of them? What became of the 2% who would require an urgent D&C for heavy bleeding? Or the 0.1% who would require a blood transfusion? What became of the 1% (and up to 9%) ongoing pregnancies ? Whatever became of these babies?

Misoprostol is a known teratogen, responsible for skull deformities, facial nerve paralysis, and limb defects. How many of these children were born severely damaged? If a very high stakes new drug trial in carefully selected clinic settings loses track of 5% of their patients, how many patients will disappear when the method is used in some local abortion clinic? How many damaged babies will result? What kind of medical care is this for women (20% of them teenagers) with a crisis pregnancy?

The 14th day visit

According to the FDA program, the purpose of the doctor visit on the 14th day of the procedure is to determine whether the abortion is complete. The abortionist is left to his/her discretion in this determination. No standard of care is recommended. The French require an ultrasound at this visit unless completed abortion is obvious. Ultrasound will document retained products of conception or ongoing pregnancy. The American medical establishment leaves this critical determination to the abortion provider’s judgment—or lack thereof. Ultimately, each abortionist will do what is right in their own sight.

In the Spitz study, 23% of women were still having significant flow (more than spotting) at day 15. Two percent of women had already had an urgent D&C for heavy bleeding by this point, and an additional 5% will have one as a result of the day 15 evaluation. Without the help of ultrasound,   the abortion provider will rely solely on what amounts to guesswork to make the decision.

The unnecessary "choice"

With pregnancies in the 5 to 7 week range, there is a normal incidence of non-viable pregnancies estimated between 5 to 10%. These will result in inevitable miscarriage, and they can easily be diagnosed ahead of time by vaginal ultrasound. There are many sensitive women who realize abortion destroys their unborn child, but who feel forced by circumstance to have the procedure anyway. Many of these women will suffer life long emotional agony because of their "choice." Had they known their pregnancy was not living and would miscarry, they would have been spared the "abortion experience" with its accompanying agony of conscience. The Post Abortion Syndrome is a devastating reality, involving immense emotional pain.

Breast Cancer Risk

There is compelling evidence that induced abortion is associated with
subsequent increased breast cancer risk. It has long been known that early full term pregnancy confers a degree of protection against breast cancer. Interrupting the pregnancy results in loss of that protection. But additionally, 13 of 15 (80%) of American studies , and 28 of 37 (75%) of world wide studies have confirmed at least a 30% increase in breast cancer among aborted women when compared to their non-aborted peer group. Teenagers and women with a positive family history of breast cancer are even more at risk for future breast cancer. Mifeprex, like surgical abortion, abruptly interrupts the pregnancy and its hormone effect on breast tissue proliferation. It is very possible, even probable, that a similar increased risk of breast cancer will also be associated with this form of induced abortion. And women, even decades later, will suffer as a result of their abortion choice.

The Approval Process

The very approval process used by the FDA involves scientific dishonesty and a duplicity of standards. Mifeprex was approved on a fast track policy (Accelerated Approval of New Drugs for Serious or Life Threatening Illnesses). This policy is designed for rapid approval of drugs that might be life saving for patients with otherwise lethal diseases (such as AIDS). Pregnancy obviously does not fit this "life threatening" illness category.

And Mifeprex is anything but a "life saving" medication. The safety data was based on American studies that required ultrasound screening for gestational age and exclusion of ectopic pregnancy; yet the approved protocol does not require such screening. This does not make sense. Because the fast track approval category for Mifeprex involves weakened liability implications for drug companies, women injured by the drug may have a very difficult time recovering damages. In addition, the Chinese manufacturer of Mifeprex has a past record with the FDA of marketing drugs with impurities, and of inaccurate labeling. Recovering damages from this mainland China firm will probably not be possible. American women will not be

well served by this approval/ manufacturing scheme.

The "feeling of control"

And finally, there is the "feeling of control" being suggested to American women considering the Mifeprex "solution." Volume 44 of ACOG TODAY, Issue 10 Nov-Dec 00 quotes a woman doctor, a leading proponent of Mifeprex abortion, as stating, "Women like it because it permits them to feel in control of the process." While this may be true of some women, it is our contention that many will feel anything but "in control." They do not know when they will abort; they do not know IF they will abort; they do not know how much bleeding will occur; they do not know how much bleeding is too much bleeding; they do not know if their pain is expected or excessive; they do not know if what they just passed is a baby or a blood clot; they do not know if they have an ectopic that is rupturing; they do not know if they are in the 2% who will require an emergency D&C; or if they are in the 0.1% who will need a blood transfusion to save their lives. "Feel in control" indeed! And all the while they are thinking, "I have done this to myself, I have done this to my unborn child."

"Reproductive Health"

Because the pool of surgical abortion providers is shrinking, and access to elective abortion is shrinking with it, there is a very strong drive by
"choice" advocates and abortion advocates to promote pharmaceutical abortion. So urgent and powerful is this drive that it has eclipsed common sense and appropriate standards of care in favor of availability of and ease of access to abortion. And as a result of the loosened standards of care, women will needlessly suffer complications and even death.
[The American Association of Pro-Life Obstetricians and Gynecologists]