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Add ella to options for emergency contraception
(Editor's note: This story discusses off-label use of emergency contraception.)
Get ready to add another option to the list of emergency contraception (EC) methods. The Food and Drug Administration has approved ella (ulipristal acetate, UPA) tablets. The drug, which will be available by prescription only, prevents pregnancy when taken orally within 120 hours (five days) after a contraceptive failure or unprotected intercourse.
Ella is a progesterone agonist/antagonist whose likely main effect is to inhibit or delay ovulation. Since May 2009, the prescription product has been available in Europe through Paris-based HRA Pharma under the brand name ellaOne. Ella will be launched and marketed in the United States later in 2010 by HRA Pharma's partner Watson Pharma of Morristown, NJ.
"Ella, or UPA, is safe and effective at preventing ovulation and therefore pregnancy in the five days after unprotected intercourse," said Vanessa Cullins, MD, MPH, vice president for medical affairs at the New York City-based Planned Parenthood Federation of America in a statement following the Aug. 13, 2010, regulatory approval.1 "Given the fact that half of all pregnancies in the U.S. are unintended, it is vital that women have an array of choices available to prevent unplanned pregnancy," Cullins said. "Ella will become an important option for women."
Check the science
Two multicenter clinical studies were used to evaluate ella's efficacy and safety. An open-label study provided the primary data to support the use of the drug when taken 48-120 hours after unprotected intercourse. A single-blind comparative study looked at use of the drug when taken 0-72 hours after unprotected intercourse, as well as provided supportive data for drug use when it is taken more than 72-120 hours after unprotected intercourse. Women in both studies were required to have a negative pregnancy test prior to receiving emergency contraception.
The open-label study was a multicenter open-label trial conducted at 40 U.S. family planning clinics. Participants in the trial included healthy women with a mean age of 24 who requested emergency contraception 48-120 hours after unprotected intercourse. The median body mass index (BMI) for the study participants was 25.3 and ranged from 16.1 to 61.3 kg/m.2
Twenty-seven pregnancies occurred in 1,242 women ages 18-35 who were evaluated for efficacy. The number of pregnancies expected without emergency contraception was calculated based on the timing of intercourse with regard to each woman's menstrual cycle. Ella reduced the pregnancy rate from an expected rate of 5.5% to an observed rate of 2.2%, when taken 48-120 hours after unprotected intercourse.
The second study was designed as a multicenter, single-blind, randomized comparison of the efficacy and safety of 30 mg ulipristal acetate to levonorgestrel. Study participants were enrolled at 35 sites in the United States, the United Kingdom, and Ireland, with most (66%) in the United States. Healthy women with a mean age of 25 who requested emergency contraception within 120 hours of unprotected intercourse were enrolled and randomly allocated to receive ella or 1.5 mg of levonorgestrel. Median BMI for the study subjects was 25.3 and ranged from 14.9 to 70.0 kg/m.2
A total of 16 pregnancies occurred in 844 women ages 16 to 35 years in the ella group when the drug was taken 0-72 hours after unprotected intercourse. The number of pregnancies expected without emergency contraception was calculated based on the timing of intercourse with regard to each woman's menstrual cycle. Ella reduced the pregnancy rate from an expected 5.6% to an observed 1.9%, when taken within 72 hours after unprotected intercourse. Researchers report no pregnancies were observed in the women who were administered ella more than 72 hours after unprotected intercourse (10% of women who received ella).2
Scientists pooled data from the two studies to calculate a total efficacy population of women treated with ulipristal acetate up to 120 hours after unprotected intercourse. Analysis for the five 24-hour intervals from 0-120 hours between unprotected intercourse and treatment was conducted. There were no significant differences in the observed pregnancy rates across the five time intervals, researchers report.2
Subgroup analysis of the pooled data by BMI showed that for women with BMI of more than 30 kg/m2 (16% of all subjects), the observed pregnancy rate was 3.1% [95% confidence interval (CI): 1.7, 5.7], which was not significantly reduced compared to the expected pregnancy rate of 4.5% in the absence of emergency contraception taken within 120 hours after unprotected intercourse. In the comparative study, a similar effect was seen for the levonorgestrel comparator emergency contraception drug. For levonorgestrel, when used by women with BMI more than 30 kg/m2, the observed pregnancy rate was 7.4% (95% CI: 3.9, 13.4), compared to the expected pregnancy rate of 4.4% in the absence of emergency contraception taken within 72 hours after unprotected intercourse.2
More time for action
There are many reasons that women do not make it into a pharmacy immediately for EC after unprotected sex, said Aimee Gallagher, MPH, director of communications and policy of the Washington, DC-based National Association of Nurse Practitioners in Women's Health, in a statement during the FDA's July 2010 reproductive health committee.3 Adding ella increases women's options for dealing with the possibility that they might have been exposed to an unintended pregnancy, she noted.
Ulipristal acetate has been shown to be effective for up to five days, versus 72 hours with the current method of emergency contraception, said Gallagher. Both Plan B One-Step (Teva Women's Health, Woodcliff Lake, NJ) and Next Choice (Watson Pharmaceuticals) are indicated to be taken as soon as possible within 72 hours after unprotected intercourse.
"Perhaps this product will take some of the 'emergency' out of emergency contraception and allow more access to women in this situation," said Gallagher.
According to Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta, the labeling of ella for use up to 120 hours is no advantage over the currently available EC pills, except it is directly stated in the labeling. As noted in the chapter on emergency contraception in the current edition of Contraceptive Technology, treatment effectiveness of EC pills has been documented through 120 hours.4-8
Emergency insertion of a copper T intrauterine device (ParaGard IUD, Teva Women's Health) is significantly more effective than use of EC pills, reducing the risk of pregnancy following unprotected intercourse by as much as 99%.9-10
According to Contraceptive Technology, the copper-bearing intrauterine device as emergency contraception can be inserted up to five days after ovulation. Most family planning providers, however, limit insertion to the first five days after intercourse because it is difficult to reliably estimate the day of ovulation. If emergency IUD insertion is planned, but cannot be carried out immediately, provide EC in pill form when the woman is initially evaluated.4