SEARLE OPPOSES ITS USE FOR ABORTION Searle Company Warns Of

SEARLE OPPOSES ITS USE FOR ABORTION
Searle Company Warns Of "Serious Adverse Events" With Off-Label Use of Cytotec

By Randall K. O'Bannon, Ph.D.

With a decision by the U.S. Food and Drug Administration (FDA) whether to authorize American marketing of RU486 looming, G.D. Searle, the maker of a second drug currently used in conjunction with the abortion pill, has released a letter saying it has received reports of "serious adverse events" with off-label uses of its prostaglandin Cytotec and does not support its use for abortion

Searle developed Cytotec to help prevent gastric ulcers among people, such as those suffering from arthritis, who have to take a lot of nonsteroidal anti-inflammatory drugs (aspirin, etc.). Despite its widespread use in conjunction with RU486, Searle has never sought to have Cytotec approved for this use. Indeed, Searle includes in its labeling a warning that it is not to be used by women who are pregnant because it can cause an abortion.

The words "RU486" or "abortion pill" are commonly used as shorthand to describe the chemical abortion technique first used in France in the 1980s. Not commonly recognized is that because the " success" rate is not high enough when RU486 is used alone, almost always at least one other drug, a prostaglandin, is also used.

To understand why requires a brief explanation of how RU486 works. RU486 is a powerful artificial steroid that blocks the action of progesterone, the hormone responsible for maintaining the nourishing, protective uterine environment needed by the baby in early pregnancy. However, RU486 does not always kill the unborn baby and/or cause the child's shriveled body to be expelled. Thus, a prostaglandin is usually employed because it stimulates the powerful uterine contractions that actually expel the dead or dying baby.

In the 1980s, when the RU486 pill was first approved for use in France and Britain, abortionists initially used the prostaglandins gemeprost or sulprostone. However, when they began to encounter problems with their use,1 they began to switch over to misoprostol, a milder prostaglandin marketed by G.D. Searle.

Misoprostol's trade name is Cytotec. In recent U.S. trials misoprostol/Cytotec was the prostaglandin used in conjunction with RU486.

As mentioned above, Searle has never sought to have Cytotec approved for this use. Searle went to the press in 1993 when abortionists began regularly using their product to complete RU486 abortions. Though, legally, doctors have the right to use FDA-approved drugs however they see fit (so-called "off label" use), the pharmaceutical company sought in a letter to the Wall Street Journal to make clear that "Searle strongly opposes any efforts to approve its use with RU486 in abortion, either in the U.S. or elsewhere" (3/19/93).

Ignoring those objections, doctors have not only continued pairing Cytotec with RU486, but have also begun to experiment using Cytotec by itself for a number of other "off label," or unapproved, applications, including abortion uses. They include use as a labor inducer, as a cervical ripener (to loosen the cervix so that the baby may pass through), or even as an agent to induce first- or second-trimester abortions.

It is because of this last application, a story in the August 30- September 5, 2000, edition of the Village Voice reports, that a sizeable black market has grown up around Cytotec. Often referred to as "the star pill" on the streets because of its five- sided shape, the drug has put a number of women into hospital emergency rooms hemorrhaging or dealing with the effects of an incomplete abortion, the Village Voice reports.

Against this backdrop, and with an FDA ruling on the marketing application of RU486 scheduled by September 30, Searle has issued a physician alert under the heading "Important Drug Warning Concerning Unapproved Use of Intravaginal or Oral Misoprostol in Pregnant Women for Induction of Labor or Abortion."

Addressed to "health care practitioners," the August 23, 2000, letter reminds doctors that Cytotec is "contraindicated" (i.e., not medically appropriate) for pregnant women "because it can cause abortion" and reemphasizes that "Cytotec is not approved for the induction of labor and abortion."

Searle indicates that it is aware that there are those using its product for "induction of labor" and for "cervical ripening prior to termination of pregnancy," but warns doctors that "Serious adverse events" including "maternal and fetal death" and "uterine hyperstimulation, rupture, and perforation" have been associated with "off-label" uses of the drug.

Searle says in its physician alert that the company has not conducted research on Cytotec for these uses and has no intention of doing so. It also warns, "In addition to the known and unknown acute risks to mother and fetus, the effect of Cytotec on the later growth, development, and functional maturation of the child when Cytotec is used for induction of labor or cervical ripening has not been established." 2

The August 28, 2000, edition of Health News Daily reports that Searle's letter was jointly drafted with the FDA, the same government agency set to rule on the marketing application for RU486 before the end of September.

Though the timing of the letter seems somewhat suspicious, with a decision on the RU486/Cytotec combo just around the corner, Searle spokeswoman Claudia Clovitz told the Wall Street Journal that the timing of the warning letter was "purely coincidental" (9/5/00). Clovitz said discussions on strengthening the warning label had been underway for some time, and that the release had nothing to do with the agency's pending decision on RU486.

Receiving an application for RU486 in March 1996, the FDA was originally supposed to rule within six months.

The agency has twice granted two "approvable" letters to RU486 indicating it was satisfied with the safety and effectiveness of the drug. However, the FDA withheld final approval pending the resolution of certain "manufacturing" and "labeling" issues (according to the 1996 letter) or other publicly unspecified procedural questions (according to the 2000 letter).

Though the FDA itself has not released any information, sponsors of the pill have reportedly told members of the abortion community that the FDA is proposing a series of restrictions as a condition of approval. These are said to include limiting prescription to doctors trained in use of the drug, who are trained in the reading of ultrasounds, and who have training or experience in the performance of surgical abortions, as a backup in case of complications or if the drugs fail. Other proposals include monitoring distribution, conducting follow-up studies, and requiring that physicians have access to hospitals with emergency services within an hour's drive of their offices.

(See the June 2000 issue of NRL News, or for more extensive detail on the proposed regulations, see the newly added material to the RU486 web site found at www.nrlc.org/ru486all.html.)

While the abortion lobby cast these regulations as unnecessary " political interference," and has gained some backing from the medical community for this charge (see sidebar), the FDA has maintained that it has a responsibility "to examine not only whether [a] product is effective, but whether it can be used safely" (USA Today, 6/7/00). In this respect, the warning from Searle bolsters the FDA case regarding the need for protective regulations.

This raises a series of sticky questions for the FDA, however. If it does decide to go ahead and approve the RU486/Cytotec abortifacient combination, does the FDA force Searle to change the labeling on Cytotec to allow its use for abortion - - to identify this as safe, appropriate use, even after helping draft the letter that raised serious safety concerns about Cytotec's use for these sort of applications? Or does the FDA just leave Searle's objections on the table and authorize this as an approved off-label use, leaving the status of the drug for this application in some sort of legal limbo land?

In any case, this latest warning from Searle provides more evidence than ever that both women and their unborn children will be better off if the two-drug abortion cocktail is never approved. Whether the FDA will heed the warning is unclear.

What is clear, however, from Searle's letters is that if the approval does come, it will entail the use of Cytotec for purposes Searle finds objectionable and considers dangerous.

NOTES

1. One woman died and at least two others suffered "cardiac events" after taking the RU 486/sulprostone combination in France.

2. For reports on some of the developmental malformations associated with failed misoprostol (Cytotec) abortions in Brazil, see NRL News articles from June 9, 1998, and July 8, 1998.

Searle Letter:
Complications reported from misuse of Cytotec
* maternal or fetal death
* uterine hyperstimulation, rupture, or perforation requiring uterine surgical repair, hysterectomy, or salpingophorectomy [removal of fallopian tubes and ovaries]
* amniotic fluid embolism
* severe vaginal bleeding
* retained placenta
* shock
* fetal bradycardia
* pelvic pain