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FDA Public Health Advisory
Sepsis and Medical Abortion Update
March 17, 2006

The Food and Drug Administration has been informed of two additional deaths following medical abortion with mifepristone (Mifeprex). The Agency received verbal notification of the deaths in the United States from the manufacturer, Danco Laboratories. At this time we are investigating all circumstances associated with these cases and are not able to confirm the causes of death. However, all providers of medical abortion and their patients need to be aware of the specific circumstances and directions for use of this drug and all risks including sepsis when considering treatment. In particular, physicians and their patients should fully discuss early potential signs and symptoms that may warrant immediate medical evaluation.

The approved Mifeprex regimen for a medical abortion through 49 days’ 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.

These recommendations are consistent with warnings in the Prescribing Information and information for the patient in the Medication Guide. FDA also emphasizes that healthcare professionals and patients should be aware of the following:

* All providers of medical abortion and emergency room health care providers should investigate the possibility of sepsis in patients who are undergoing medical abortion and present with nausea, vomiting, or diarrhea and weakness with or without abdominal pain, and without fever or other signs of infection more than 24 hours after taking misoprostol. To help identify those patients with hidden infection, strong consideration should be given to obtaining a complete blood count.

* FDA recommends that physicians suspect infection 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. 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.

As previously provided in our July 19, 2005 Public Health Advisory, updated on November 4, 2005, the Agency is aware of four previous confirmed deaths from sepsis in the United States, from September 2003 to June 2005, in women following medical abortion with mifepristone (Mifeprex) and misoprostol. All four cases of fatal infection tested positive for Clostridium sordellii. All four cases involved the off-label dosing regimen consisting of 200 mg of oral Mifeprex followed by 800 mcg of intra-vaginally placed misoprostol. In addition, FDA tested drug from manufacturing lots of mifepristone and misoprostol and found no contamination with Clostridium sordellii.

We do not know whether these new deaths were caused by sepsis or, if they were, if they were caused by infection with Clostridium sordellii. However, FDA, in conjunction with the Centers for Disease Control and Prevention (CDC) and the National Institute of Allergy and Infectious Diseases (NIAID), is conducting a public workshop on May 11, 2006. This scientific workshop entitled, “Emerging Clostridial Disease,” at the CDC Conference Center, Atlanta, Georgia, is being conducted to discuss the scientific and medical circumstances associated with reports of morbidity and mortality associated with C. sordellii and C difficile infections. These reports include cases and clusters of C. sordellii toxic shock syndrome following treatment with mifepristone, C. sordellii sepsis associated with skin grafts, and rapidly fatal toxin-mediated cases of community-associated C. difficile infection. The primary goal of the workshop is to bring together scientific and public health experts to develop a draft research agenda leading to a better understanding of the virulence, pathogenesis, host factors, and non-antimicrobial risk factors contributing to those reports.

Information pertaining to Mifeprex can be found at http://www.fda.gov/cder/drug/infopage/mifepristone/default.htm

Information pertaining to Emerging Clostridial Diseases Public Workshop can be found at http://www.fda.gov/cder/meeting/clostridia_disease.htm


Date created: March 17, 2006


And a related article, posted here:


Abortion Pill Slated for New FDA Review
By Rebecca Vesely
Women's eNews

Thursday 23 February 2006

The FDA is about to begin a new review of the abortion pill RU-486, which some have blamed for the sudden deaths of four American women. A scientific review of the cases fails to definitively link the drug to the fatalities.

The long-simmering controversy over the abortion pill RU-486 is expected to come to a boil in May when the Food and Drug Administration convenes a scientific conference in Atlanta over the safety of the drug regimen used to terminate early pregnancies.

The meeting was prompted in part by the recent and sudden deaths of four young California women after taking RU-486, sold under the brand name Mifeprex.

All four women died in the past three years from toxic shock syndrome brought on by a bacterium called Clostridium sordellii just days after taking Mifeprex and a follow-up drug, misoprostol. The women, ranging from age 18 to age 34, were healthy and vibrant, with no previous medical problems. In all cases, the bacterial infection swiftly took these women's lives, with the absence of typical symptoms of infection.

"Women are playing Russian roulette with their lives when they take this drug," says Monty Patterson, father of 18-year-old Holly Patterson, who died in 2003 just days after taking Mifeprex at a Planned Parenthood near San Francisco to terminate a seven-week pregnancy.

Like the three other women who died after taking Mifeprex, Holly Patterson had neither a fever nor abdominal tenderness, typical signs of infection. She was treated with painkillers at a local emergency room for severe abdominal cramping and released. She returned three days later, complaining of nausea, vomiting and weakness. She had low blood pressure and an elevated heart rate. She died about 10 hours after admission.

Reproductive rights advocates fear that the day-long scientific meeting could turn political and that anti-choice forces will take the abortion pill down the same path as Plan B, the emergency contraception that was denied over-the-counter status by the FDA despite scientific evidence to its safety and efficacy.

"There's a large clinical and scientific consensus that the benefits far outweigh the risks" of Mifeprex, said Kirsten Moore, president and CEO of the Reproductive Health Technologies Project in Washington, D.C., a group that was founded in 1988 to advance public understanding of RU-486.

'Holly's Law' Could Ban Drug

Since his daughter's death, Monty Patterson has been on a crusade to learn all he can about the safety of the abortion pill and to lobby for its removal from the US market. Members of Congress are pushing for "Holly's Law," a bill now in a House subcommittee with nearly 80 co-sponsors that would suspend the drug's approval pending further investigation.

"The health, safety and welfare of women should never be this compromised," Patterson said. "Women need to completely understand the health consequences of this drug to make an informed decision."

Patterson says he is not anti-choice and calls surgical abortion a safer alternative to the abortion pill. Several of the women's families, including Patterson, are suing Danco Laboratories, the New York-based US manufacturer of Mifeprex.

In a New England Journal of Medicine article published in October, Dr. Marc Fischer, medical epidemiologist at the Atlanta-based Centers for Disease Control and Prevention, described in detail the four cases and their striking similarities. But he was unable to draw a conclusive link between Mifeprex and the onset of the lethal bacterial infection.

"It seems there is potentially something related to being pregnant that may be associated with this bacteria," Fischer said, noting that eight other women died after developing Clostridium sordellii infections during pregnancy.

Not Approved in Canada

In the only other reported case in scientific literature of those infections in the genital tract, a Canadian woman enrolled in a clinical trial for Mifeprex died from associated toxic shock. As a result of that death, Mifeprex has never been approved for use in Canada.

Fischer and his co-authors speculate that pregnancy or abortion may predispose a small number of women to acquire the bacteria. In addition, a low pH level - to indicate acidity - in the vaginal tract may be conducive to the secretion of the lethal toxins, Fischer said.

"These were such unique and extreme cases," said Fischer, who is scheduled to speak at the May scientific conference.

The Centers for Disease Control, working with the FDA, is investigating other factors that could have contributed to the women's deaths. The pills they took were not from the same lots and investigators found no evidence of tampering.

Fischer speculated that the California cluster could be attributed to strong media attention surrounding Holly Patterson's death and perhaps to higher abortion pill usage patterns in that state.

Some theorize that the way the protocol is routinely administered may play a role. Most abortion providers give 200 milligrams of Mifeprex to women orally, then instruct them to take 800 milligrams of misoprostol vaginally at home. Mifeprex blocks the hormone necessary for pregnancy, while misoprostol induces uterine contractions.

Practitioners Use Different Protocol

This standard protocol used by practitioners is different from the one approved by the FDA when Mifeprex was legalized in 2000. Under the approved protocol, Mifeprex is given at a higher dose and misoprostol is given orally at a lower dose.

Leading abortion providers and health professionals, including Planned Parenthood, defend Mifeprex and the protocol used to administer it. More than 460,000 doses of Mifeprex have been sold to abortion providers in the United States since its approval by the FDA in 2000. Another 500,000 women in 35 countries have used the abortion pill to terminate pregnancies of up to eight weeks, but there is no data on fatality rates.

The deaths have prompted Danco Laboratories to strengthen its black box warning on Mifeprex's label to include information about unusual signs of infection that don't include fever.

The scientific meeting could touch off a political debate reminiscent of the firestorm surrounding Plan B, the emergency contraception pill. The Government Accountability Office in November released a report charging that the FDA didn't follow its own procedures when it denied Plan B over-the-counter status, indicating that political appointees trumped scientific staff.

Moore of the Reproductive Health Technologies Project said the FDA has become too politicized. "Plan B was just flat-out jaw-dropping. I can't believe they just did that, that they played with women's health that way," Moore said. "The integrity of the agency is absolutely in question."

Patterson hopes to speak at the Mifeprex meeting and present scientific evidence, which he has spent the past two years compiling, though it is unclear whether he will be invited to the podium. "This is a lethal choice," Patterson says of Mifeprex. "I will never think it is safe."

Rebecca Vesely is a health care reporter at the Oakland Tribune.

Comments

[cammie018.livejournal.com]

Ya know, all this information is practically writing my paper on the history of birth control, keep going :)

In that case...

[treeskin.livejournal.com]

Check out this discussion (http://www.metafilter.com/mefi/50162) on Metafilter. May have more useful stuff for you. And I'll keep posting what I find for you.

How soon does that paper need to be written?