Deaths

OVERVIEW OF MEDICAL ABORTION DEATHS

What does the FDA know about medical abortion deaths from mifepristone and misoprostol?

Mifeprex (mifepristone) 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). ⁽¹⁾

Since mifepristone’s approval in September 2000, the U.S. Food and Drug Administration (FDA) has received reports of serious adverse events, including women who have died, in the United States and other countries following medical abortion with mifepristone and misoprostol. ⁽²⁾

As previously reported by the FDA, several of the women who died in the United States died from sepsis (severe illness caused by infection of the bloodstream) after medical abortion. ⁽¹⁾

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. ⁽¹⁾

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. ⁽¹⁾

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). ⁽¹⁾

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. ⁽¹⁾

Please see the WARNINGS in the Prescribing Information and information for the patient in the MEDICATION GUIDE for Mifeprex (mifepristone).

The safety and effectiveness of other Mifeprex (mifepristone) dosing regimens, including use of oral misoprostol tablets intravaginally, has not been established or approved by the FDA. ⁽¹⁾

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.

International Medical Abortion Deaths – All Causes Reported

Update: October 10, 2013 – Total Reported Deaths following Mifepristone/Misoprostol Medical Abortion

Since 2001, at least twenty-two women worldwide have died from fatal complications including hemorrhage, toxic shock, sepsis, organ failure, and ruptured ectopic pregnancy following early medical abortion with mifepristone and misoprostol. ^{(2) (3) (15) (16) (21) (22) (23)}

There have been media reports of a European manufacturer's mention of the potential for additional deaths due to mifepristone and misoprostol medical abortion. It appears there is an official lack of documentation at this time.

International Medical Abortion Deaths – Sepsis/Toxic Shock

Update: October 10, 2013 – Total Sepsis/Toxic Shock Deaths following Mifepristone/Misoprostol Medical Abortion

Bacterial Infections and sepsis (a serious infection involving the bloodstream)

Since 2001, twelve women—one in Canada, eight in the United States, one in Portugal, one in Australia, and one in the United Kingdom (England)—have died from sepsis/toxic shock syndrome (nine from Clostridium sordellii, one from Clostridium perfringens, one from Group A Streptococcus, one from Clostridium septicum) following early medical abortions with mifepristone and misoprostol. ^{(1) (2) (3) (4) (5) (6) (7) (9) (15) (16) (18) (19) (22) (23)}

Type of Medical Abortion Drug Regimens

• Ten women were administered a regimen of 200 mg mifepristone orally followed by 800 mcg misoprostol vaginally (drug inserted into the vagina).
• One woman was administered a regimen of 200 mg mifepristone orally followed by 800 mcg misoprostol buccally (drug placed between the gum and cheek).
• One woman’s mifepristone/misoprostol regimen was not reported to the public.

Type of Infectious Diseases Following Medical Abortion

• Nine women tested positive for Clostridium sordellii, (eight women used vaginal misoprostol, one woman used buccal misoprostol).
• One woman tested positive for Clostridium perfringes sepsis, (the woman used vaginal misoprostol).
• One woman was reported to have died from Group A Streptoccus sepsis, (misoprostol’s placement or insertion was not reported).
• One woman tested positive for Costridium septicum.  (two vaginal misoprostol doses were used)

In 2001, clinical trials in Canada were suspended after the death of a Canadian woman from clostridium sordelli toxic shock after initiation of medical abortion with 200 mg mifepristone orally followed by 800 mcg of vaginal misoprostol. ⁽²⁰⁾

In 2003-2009, all eight women in the United States (U.S.) who had died from sepsis/toxic shock after initiation of mifepristone/misoprostol medical abortion were provided an off-label drug regimen not approved or recognized by the U.S. Food and Drug Administration: ^{(2) (4) (5) (6) (7)}

In 2010, Australia, the first medical abortion death of a woman was later reported by the media in 2012. The woman died from Group A Streptococcus sepsis after initiation of an unapproved/non-registered regimen of mifepristone and misoprostol. ^{(15) (16)}

In 2011, Portugal, the first Clostridium sordellii toxic shock death of a 16 year-old woman, who died after initiation of 200 mg mifepristone orally followed by 800 mcg misoprostol vaginally. It is not known if the regimen was registered or approved by local authorities. ⁽³⁾

In 2013, United Kingdom – England, the first reported international case of Clostridium septicum sepsis,death of a 31 year-old woman, who died after initiation of 200 mg mifepristone orally followed by 800 mcg misoprostol vaginally and an additional dose of 400 mcg misoprostol vaginally 4 hours thereafter.^{(22) (23)}

2013 FIRST INTERNATIONAL MEDICAL ABORTION DEATH FROM CLOSTRIDIUM SEPTICUM

United Kingdom, England, Woman Dies in 2010 from Clostridium Septicum after Medical Abortion

The July 2013 issue of Journal of Obstetrics and Gynaecology published the first-ever documented international case report of “Fatal Clostridium septicum following medical termination of pregnancy.” The patient died from a septic infection after receiving a medical abortion regimen of mifepristone (RU-486) and misoprostol. ⁽²²⁾

The medical abortion regimen administered was 200 mg mifepristone orally and then 2 days later, 800 mcg misoprostol vaginally & 400 mcg misoprostol vaginally 4 hours after that. ⁽²³⁾

The case report details the tragic death of a 31-year-old woman; who was admitted to the Royal Albert Edward Infirmary, Wigan, United Kingdom after experiencing a 1 day episode of abdominal pain and vaginal bleeding, commencing 1 month after a medical pregnancy termination at 8 weeks gestation. ^{(22) (23)}

The patient died 28 hours after admission to the hospital. ⁽²²⁾

Postmortem examination revealed inflammation and abscess formation in the uterus at the site of the previous pregnancy. There was necrosis of the skeletal muscle predominately in the thighs, with infiltration by Gram-positive organisms and no inflammatory cell infiltration. Blood cultures grew anaerobic Clostridium septicum. ⁽²²⁾

Vaginal carriage of Clostridium septicum is viewed to be the most likely source of infection in the case report of the 31-year-old United Kingdom woman, with the inflammatory focus in the uterus from the site of the terminated pregnancy thought to be the portal of entry for this organism, causing the fatal outcome. ⁽²²⁾

2012 FIRST MEDICAL ABORTION DEATH RECORDED IN AUSTRALIA – SEPSIS

Australian Woman Dies in 2010 from Group A Streptococcal Sepsis after Medical Abortion

On March 19, 2012 the local media in Australia reported a woman died in 2010 from Group A Streptococcus sepsis, a severe bacterial infection of the bloodstream – some days after being prescribed a regimen of two drugs, RU-486 (mifepristone) and misoprostol, from a Marie Stopes International Australia (MSIA) clinic. ^{(15) (16)}

The Therapeutic Goods Administration (TGA) in Australia, the regulatory authority for medical drugs and devices, released few details about the 2010 death of the unnamed woman who had been treated by the country’s largest abortion service, Marie Stopes International Australia (MSIA). ^{(15) (16)}

Both MSIA and the TGA refused to release details of the abortion pill fatality, citing respect for patient confidentiality. ⁽¹⁵⁾

In March 2012, the U.S. Food and Drug Administration (FDA) was notified of the first recorded Australian medical abortion death reportedly associated with Group A Streptococcal Sepsis (GAS) post-medical-abortion. ⁽¹⁷⁾

2011 FIRST MEDICAL ABORTION DEATH IN EUROPE FROM CLOSTRIDIUM SORDELLII

Adolescent Dies in Europe from Clostridium Sordelli Fatal Toxic Shock after Medical Abortion

In May 2011, the FDA was notified of the first European sepsis death to be associated with Clostridium sordellii fatal toxic shock syndrome post-medical-abortion in Portugal. The distinctive clinical features developed were the same reported as in other studies (See United States and Canada). ⁽³⁾

• Portugal: 2011 (report date only, actual day of death unknown), a 16-year-old adolescent girl, (name unknown), gestation period is unknown (approved medical abortion in Portugal is before 10 weeks gestation), died of a C. sordellii toxic shock syndrome approximately 5-6 days after initiation of medical abortion. ⁽³⁾

2001-2011 MEDICAL ABORTION CLOSTRIDIUM SORDELLII DEATHS

Nine Women Die in North America & Europe from Clostridium Sordelli Fatal Toxic Shock after Medical Abortion

Previous to the May 2011 report of the European (Portugal) adolescent’s death of Clostridium sordellii following medical abortion, seven other women from the United States (between the years of 2003-2009) and one woman (in 2001) from Canada were reported to have died and tested positive for same sepsis infection of Clostridium sordellii toxic shock syndrome following medical abortion with mifepristone and misoprostol. ⁽⁴⁾

In 2006, the FDA has reported the case of a tenth woman who had died of sepsis however, she had tested positive for the fatal Clostridium perfringens infection.

On April 30, 2011 the FDA released a report on 14 women who have died in the United States and 5 women who have died in foreign countries from sepsis and other fatal complications that used mifepristone for termination of early pregnancy since the FDA’s approval of medical abortion in September 2000. ⁽²⁾  Note: The European death is not included in the 4/30/2011 FDA report.

MEDICAL ABORTION DEATHS IN U.S. – SEPSIS & CLOSTRIDIUM SORDELLII

Eight Medical Abortion Deaths in U.S. Women from Sepsis

United States: 8 (eight) deaths were associated with sepsis (serious infection involving the bloodstream following medical abortion with mifepristone and misoprostol. All but one fatal sepsis case reported vaginal misoprostol use; buccal misoprostol use was reported in one case. FDA has concluded the deaths from these infections may possibly be related to the use of mifepristone and misoprostol for medical abortion. ^{(2) (4) (5) (6) (7}

Seven cases tested positive for Clostridium sordellii toxic shock syndrome following medical abortion:

• 2009-July 28, a 21-year-old previously healthy White woman (name unknown), 7 weeks (49 days) gestation, died 12 days after initiation of medical abortion.
• 2008-August 18, a 29-year-old White Hispanic woman (name unknown), 5 weeks (35 days) gestation, died 6 days after initiation of medical abortion.
• 2007-July 4, a 18-year-old previously healthy woman (name unknown), 6.5 weeks gestation (46 days), died approximately 8 days after initiation of medical abortion. Patient was administered 200 mg oral mifepristone and 800 mcg buccal misoprostol.
• 2005-June 14, a 34-year-old previously healthy White woman, Oriane Shevin, 45 days gestation, died approximately 4 days after initiation of medical abortion.
• 2004-January 14, a 22-year-old previously healthy African American woman, Chanelle Bryant, 53 days gestation, died approximately 6 days after initiation of medical abortion.
• 2003-December 29, a 21-year-old previously healthy Asian woman, Hoa Thuy “Vivian” Tran, 43 days gestation, died 5 days after initiation of medical abortion.
• 2003-September 17, a 18-year-old previously healthy White woman, Holly Patterson, 47 days gestation, died 7 days after initiation of medical abortion.

One case tested positive for fatal Clostridium perfringens infection:

• 2006-March 9, a 24-year-old previously healthy woman (name unknown), 8.5 weeks gestation, died 7 days after initiation of medical abortion.

MEDICAL ABORTION DEATHS IN U.S – OTHER COMPLICATIONS

Six Medical Abortion Deaths in U.S. Women due to Fatal Complications & Unique Events ^{(2) (8)}

Two women died from ruptured ectopic pregnancy

• 2001-September 12, a 38-year-old woman, Brenda C. Vise, approximately 6 weeks gestation, died 5 days after initiation of medical abortion. ⁽⁸⁾
• 2010, a 27-year-old woman was hospitalized and died after an induced medical abortion.

One woman died from a delayed onset of toxic shock-like syndrome where uterine cultures were positive for Peptostreptococcus and fibroid cultures were positive for Prevotella (no other information available).

One woman died from suspected homicide (no other information available).

One woman died of substance abuse/drug overdose (no other information available).

One woman died of methadone overdose (no other information available).

MEDICAL ABORTION DEATHS IN FOREIGN COUNTRIES – OTHER COMPLICATIONS

Five Medical Abortion Deaths in Women from Foreign Countries due to Fatal Complications

One death in Canada was associated with septic shock from a foreign clinical trial. This case tested positive for Clostridium sordellii toxic shock syndrome following medical abortion: ^{(9) (10)}

• 2001, September 1, a 26-year-old previously healthy woman (name unknown), 10 weeks gestation, died approximately 16 days after initiation of medical abortion.

One death in Taiwan was associated with Thrombotic thrombocytopenic purpura (TTP) leading to intracranial hemorrhage. ^{(2) (11)} TTP is a blood disorder that causes blood clots to form in small blood vessels around the body, and leads to a low platelet count. ⁽¹²⁾

• (Year Unknown, report published in 2007), a 31 year-old woman, 5 weeks (35 days) gestation, the woman had received mifepristone 200 mg orally 2 weeks previously, exact number of days until patient died after initiation of medical abortion is unclear.

One death in a Foreign Country (unnamed) was associated with ruptured gastric ulcer. ⁽²⁾

One death in a Foreign Country (unnamed) was associated with uterine hemorrhage. ⁽²⁾

One death in a Foreign Country (unnamed) was associated with multivisceral failure. ⁽²⁾

MEDICAL ABORTION DEATHS IN FOREIGN COUNTRIES – REPORTED BY THE MEDIA

Three Medical Abortions Deaths in Women from Foreign Countries Reported in the News Media

Foreign Countries: The following three women’s deaths were reported in the news media. Note: the deaths in Sweden and United Kingdom may be the same cases as those reported to the FDA (see 5 foreign deaths).

• One death in Sweden: 2003-June 3, a 16-year-old woman, Rebecca Tell Berg, approximately 7-8 weeks gestation, died 3 days after initiation of medical abortion. It was reported that she had bleed to death. ⁽¹³⁾
• One death in United Kingdom: 2005-June 27, a 18-year-old woman, Manon Jones, 6 weeks gestation, died 17 days after initiation of medical abortion. It was reported that she died from hypovolemia, an abnormal decrease in blood volume, and shock caused by retained products of conception. ⁽¹⁴⁾
• One death in Australia: 2010, no information other than the media in Australia & Therapeutic Goods Administration (TGA) reported a woman had died from Group A Streptococcus sepsis, a severe bacterial infection of the bloodstream – several days after being prescribed a medical abortion regimen of two drugs, RU-486 (mifepristone) and misoprostol. ^(15)(16)