Simultaneous Abortion Medications Match 24-Hour Dosing

LA JOLLA, CALIF. — Women choosing medical abortion through 63 days' gestation can achieve effective results with simultaneous administration of mifepristone and misoprostol, according to a study presented at the annual meeting of the Association of Reproductive Health Professionals.

“Our study shows that using simultaneous administration of 200 mg mifepristone and 800 mcg vaginal misoprostol is as effective and as acceptable to patients as a 24-hour dosing interval,” reported Dr. Mitchell Creinin, professor and director of family planning at the University of Pittsburgh.

Success, defined as complete abortion that did not require suction aspiration for any reason, did not achieve equivalency in the simultaneous group, though this assessment was limited by undersampling for this secondary outcome, he said.

The standard regimen for medical abortion, approved by the Food and Drug Administration, consists of taking 600 mg of oral mifepristone on day 1 and 400 mcg oral misoprostol 36–40 hours later. This regimen typically is used up to 49 days gestation, Dr. Creinin said.

Previous research by Dr. Eric Schaff, medical director of Planned Parenthood of Delaware, had shown that, with the newer vaginal regimen, women favor a shorter dosing interval, Dr. Creinin explained. “And we do know that during the 36–48 hour interval in the standard regimen that up to half of women will begin to bleed, which may have something to do with its acceptability as well as the desire to get things over with more quickly.”

A 2004 study compared the 23- to 25- hour interval with a 6- to 8- hour interval and showed the two to be equivalent in effectiveness. This led to the idea of simultaneous administration, Dr. Creinin said. “In our pilot studies of medical abortion regimens, we tend to look at our expulsion rate with the idea that we don't want to doom women to a surgical abortion if they really don't want it, and we can rescue them with a standard vaginal dose at 24 hours should the new method not work,” he explained. The expulsion rates in those pilot studies was around 90%, which meant the researchers could forge ahead with a trial.

The four-center study enrolled more than 1,100 women between June 2004 and April 2006, with follow-up at 7 and 14 days and phone follow-up 5 weeks post treatment “to check to see if the women had a D&C or problems that caused them to go somewhere else for care,” said Dr. Creinin. If documented expulsion had not occurred by the first follow-up visit, women were given a repeat dose of misoprostol. Of the total sample, two women withdrew prior to randomization and 2% of the women were lost to follow-up, so that the final number of women taking the drugs was 1,126.

All study centers held teleconferences with site monitoring at regular intervals and data queries came from the coordinating center, based on irregularities in the data. “We performed two interim analyses when one-third and two-thirds of the women had completed follow-up, and these analyses were structured to both look at overall efficacy and to address efficacy by gestational age to see if there were problems with continuing on with the study,” Dr. Creinin said, adding that 40% of the women had had a prior abortion, one-fourth of which were medical. Treatment was considered a failure if suction aspiration was performed for any indication.

Overall efficacy between the groups was comparable, with the standard treatment group achieving a success rate of 96.7%—just short of the expected 97% success rate—and the simultaneous administration group achieving a success rate of 95%. Also, almost every gestational age group came close to reaching statistically significant noninferiority, Dr. Creinin said.

Failures, such as continued pregnancy and persistent sac at 2 and 5 weeks were evenly distributed between the cohorts. On day 4, two women in the simultaneous group requested a D&C. The larger incidence of side effects was in the simultaneous group; though it reached statistical significance, it was deemed clinically irrelevant. These side effects included nausea, diarrhea, warmth, and chills. There was no difference in pain and acceptability scores, he said.

“We had relatively few adverse events, though interestingly, there were four transfusions in the standard treatment group. There was one heterotopic pregnancy in the simultaneous group, and five women in each group developed infections and were treated as outpatients without hospitalization,” Dr. Creinin said.

On Nov. 4, 2005, the FDA issued a Public Health Advisory “to inform the public that it is aware of four women in California who died from sepsis following medical abortion with mifepristone and misoprostol.”

In two of the cases, the culprit bacteria were identified as Clostridium sordellii, anaerobic bacteria that in rare cases are fatal. The deaths followed the off-label use of oral mifepristone and vaginal misoprostol given as 200 mg mifepristone orally followed the next day by 800 mcg misoprostol inserted vaginally.

LA JOLLA, CALIF. — Women choosing medical abortion through 63 days' gestation can achieve effective results with simultaneous administration of mifepristone and misoprostol, according to a study presented at the annual meeting of the Association of Reproductive Health Professionals.

“Our study shows that using simultaneous administration of 200 mg mifepristone and 800 mcg vaginal misoprostol is as effective and as acceptable to patients as a 24-hour dosing interval,” reported Dr. Mitchell Creinin, professor and director of family planning at the University of Pittsburgh.

Success, defined as complete abortion that did not require suction aspiration for any reason, did not achieve equivalency in the simultaneous group, though this assessment was limited by undersampling for this secondary outcome, he said.

The standard regimen for medical abortion, approved by the Food and Drug Administration, consists of taking 600 mg of oral mifepristone on day 1 and 400 mcg oral misoprostol 36–40 hours later. This regimen typically is used up to 49 days gestation, Dr. Creinin said.

Previous research by Dr. Eric Schaff, medical director of Planned Parenthood of Delaware, had shown that, with the newer vaginal regimen, women favor a shorter dosing interval, Dr. Creinin explained. “And we do know that during the 36–48 hour interval in the standard regimen that up to half of women will begin to bleed, which may have something to do with its acceptability as well as the desire to get things over with more quickly.”

A 2004 study compared the 23- to 25- hour interval with a 6- to 8- hour interval and showed the two to be equivalent in effectiveness. This led to the idea of simultaneous administration, Dr. Creinin said. “In our pilot studies of medical abortion regimens, we tend to look at our expulsion rate with the idea that we don't want to doom women to a surgical abortion if they really don't want it, and we can rescue them with a standard vaginal dose at 24 hours should the new method not work,” he explained. The expulsion rates in those pilot studies was around 90%, which meant the researchers could forge ahead with a trial.

The four-center study enrolled more than 1,100 women between June 2004 and April 2006, with follow-up at 7 and 14 days and phone follow-up 5 weeks post treatment “to check to see if the women had a D&C or problems that caused them to go somewhere else for care,” said Dr. Creinin. If documented expulsion had not occurred by the first follow-up visit, women were given a repeat dose of misoprostol. Of the total sample, two women withdrew prior to randomization and 2% of the women were lost to follow-up, so that the final number of women taking the drugs was 1,126.

All study centers held teleconferences with site monitoring at regular intervals and data queries came from the coordinating center, based on irregularities in the data. “We performed two interim analyses when one-third and two-thirds of the women had completed follow-up, and these analyses were structured to both look at overall efficacy and to address efficacy by gestational age to see if there were problems with continuing on with the study,” Dr. Creinin said, adding that 40% of the women had had a prior abortion, one-fourth of which were medical. Treatment was considered a failure if suction aspiration was performed for any indication.

Overall efficacy between the groups was comparable, with the standard treatment group achieving a success rate of 96.7%—just short of the expected 97% success rate—and the simultaneous administration group achieving a success rate of 95%. Also, almost every gestational age group came close to reaching statistically significant noninferiority, Dr. Creinin said.

Failures, such as continued pregnancy and persistent sac at 2 and 5 weeks were evenly distributed between the cohorts. On day 4, two women in the simultaneous group requested a D&C. The larger incidence of side effects was in the simultaneous group; though it reached statistical significance, it was deemed clinically irrelevant. These side effects included nausea, diarrhea, warmth, and chills. There was no difference in pain and acceptability scores, he said.

“We had relatively few adverse events, though interestingly, there were four transfusions in the standard treatment group. There was one heterotopic pregnancy in the simultaneous group, and five women in each group developed infections and were treated as outpatients without hospitalization,” Dr. Creinin said.

On Nov. 4, 2005, the FDA issued a Public Health Advisory “to inform the public that it is aware of four women in California who died from sepsis following medical abortion with mifepristone and misoprostol.”

In two of the cases, the culprit bacteria were identified as Clostridium sordellii, anaerobic bacteria that in rare cases are fatal. The deaths followed the off-label use of oral mifepristone and vaginal misoprostol given as 200 mg mifepristone orally followed the next day by 800 mcg misoprostol inserted vaginally.

LA JOLLA, CALIF. — Women choosing medical abortion through 63 days' gestation can achieve effective results with simultaneous administration of mifepristone and misoprostol, according to a study presented at the annual meeting of the Association of Reproductive Health Professionals.

“Our study shows that using simultaneous administration of 200 mg mifepristone and 800 mcg vaginal misoprostol is as effective and as acceptable to patients as a 24-hour dosing interval,” reported Dr. Mitchell Creinin, professor and director of family planning at the University of Pittsburgh.

Success, defined as complete abortion that did not require suction aspiration for any reason, did not achieve equivalency in the simultaneous group, though this assessment was limited by undersampling for this secondary outcome, he said.

The standard regimen for medical abortion, approved by the Food and Drug Administration, consists of taking 600 mg of oral mifepristone on day 1 and 400 mcg oral misoprostol 36–40 hours later. This regimen typically is used up to 49 days gestation, Dr. Creinin said.

Previous research by Dr. Eric Schaff, medical director of Planned Parenthood of Delaware, had shown that, with the newer vaginal regimen, women favor a shorter dosing interval, Dr. Creinin explained. “And we do know that during the 36–48 hour interval in the standard regimen that up to half of women will begin to bleed, which may have something to do with its acceptability as well as the desire to get things over with more quickly.”

A 2004 study compared the 23- to 25- hour interval with a 6- to 8- hour interval and showed the two to be equivalent in effectiveness. This led to the idea of simultaneous administration, Dr. Creinin said. “In our pilot studies of medical abortion regimens, we tend to look at our expulsion rate with the idea that we don't want to doom women to a surgical abortion if they really don't want it, and we can rescue them with a standard vaginal dose at 24 hours should the new method not work,” he explained. The expulsion rates in those pilot studies was around 90%, which meant the researchers could forge ahead with a trial.

The four-center study enrolled more than 1,100 women between June 2004 and April 2006, with follow-up at 7 and 14 days and phone follow-up 5 weeks post treatment “to check to see if the women had a D&C or problems that caused them to go somewhere else for care,” said Dr. Creinin. If documented expulsion had not occurred by the first follow-up visit, women were given a repeat dose of misoprostol. Of the total sample, two women withdrew prior to randomization and 2% of the women were lost to follow-up, so that the final number of women taking the drugs was 1,126.

All study centers held teleconferences with site monitoring at regular intervals and data queries came from the coordinating center, based on irregularities in the data. “We performed two interim analyses when one-third and two-thirds of the women had completed follow-up, and these analyses were structured to both look at overall efficacy and to address efficacy by gestational age to see if there were problems with continuing on with the study,” Dr. Creinin said, adding that 40% of the women had had a prior abortion, one-fourth of which were medical. Treatment was considered a failure if suction aspiration was performed for any indication.

Overall efficacy between the groups was comparable, with the standard treatment group achieving a success rate of 96.7%—just short of the expected 97% success rate—and the simultaneous administration group achieving a success rate of 95%. Also, almost every gestational age group came close to reaching statistically significant noninferiority, Dr. Creinin said.

Failures, such as continued pregnancy and persistent sac at 2 and 5 weeks were evenly distributed between the cohorts. On day 4, two women in the simultaneous group requested a D&C. The larger incidence of side effects was in the simultaneous group; though it reached statistical significance, it was deemed clinically irrelevant. These side effects included nausea, diarrhea, warmth, and chills. There was no difference in pain and acceptability scores, he said.

“We had relatively few adverse events, though interestingly, there were four transfusions in the standard treatment group. There was one heterotopic pregnancy in the simultaneous group, and five women in each group developed infections and were treated as outpatients without hospitalization,” Dr. Creinin said.

On Nov. 4, 2005, the FDA issued a Public Health Advisory “to inform the public that it is aware of four women in California who died from sepsis following medical abortion with mifepristone and misoprostol.”

In two of the cases, the culprit bacteria were identified as Clostridium sordellii, anaerobic bacteria that in rare cases are fatal. The deaths followed the off-label use of oral mifepristone and vaginal misoprostol given as 200 mg mifepristone orally followed the next day by 800 mcg misoprostol inserted vaginally.