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More data emerge on emergency contraception
For women who request emergency contraception, ulipristal acetate might be an effective alternative to levonorgestrel, according to results of a new study.1 Manufacturers are seeking U.S. approval of the drug.
Watson Pharmaceuticals of Corona, CA, and HRA Pharma of Paris have announced an exclusive licensing agreement for Watson to become the commercial partner for ulipristal acetate, now marketed by HRA Pharma in Europe as ellaOne.
The drug is now at the New Drug Application stage with the Food and Drug Administration. Manufacturing officials are hopeful that the agency will act on the application in 2010, says Patty Eisenhaur, Watson's vice president of investor relations and corporate communications.
Review the findings
For the current study, researchers at 35 family planning clinics in the United Kingdom, Ireland, and the United States enrolled women with regular menstrual cycles who presented requesting emergency contraception within five days of unprotected sexual intercourse. To conduct the randomized, multicenter, noninferiority trial, a total of 2,221 women were randomly assigned to receive a single, supervised dose of 30 mg ulipristal acetate (n = 1,104) or 1.5 mg levonorgestrel (n = 1,117). Follow-up was done five to seven days after expected onset of next menses.
Scientists designated the primary endpoint as pregnancy rate in women who received emergency contraception within 72 hours of unprotected sexual intercourse, with a noninferiority margin of 1% point difference between groups (limit of 1.6 for odds ratio). Analysis was done on the efficacy-evaluable population, which excluded women lost to follow-up, those over age 35, women with unknown follow-up pregnancy status, and those who had re-enrolled in the study. Researchers also used a meta-analysis of the trial and an earlier study to assess the efficacy of ulipristal acetate compared with levonorgestrel.2
In the efficacy-evaluable population, 1,696 women received emergency contraception within 72 hours of sexual intercourse; 844 women received ulipristal acetate, while 852 received levonorgestrel. Researchers recorded 15 pregnancies in the ulipristal acetate group [1.8%, 95% confidence interval (CI) 1.0-3.0] and 22 in the levonorgestrel group [2.6%, 1.7-3.9; odds ratio (OR) 0.68, 95% CI 0.35-1.31]. In the 203 women who received emergency contraception 72-120 hours after sexual intercourse, there were three pregnancies, all which occurred in the levonorgestrel group.
Researchers report the most frequent adverse event was headache [ulipristal acetate, 213 events (19.3%) in 1,104 women; levonorgestrel, 211 events (18.9%) in 1,117 women]. Two serious adverse events were judged as possibly related to use of emergency contraception: a case of dizziness in the ulipristal acetate group and a molar pregnancy in the levonorgestrel group.
In the meta-analysis, scientists recorded 22 (1.4%) pregnancies in 1,617 women in the ulipristal acetate group, and 35 (2.2%) pregnancies in 1,625 women in the levonorgestrel group (OR 0.58, 0.33-0.99; p = 0.046).1
How do they compare?
For women who presented on the fourth or fifth day after sexual intercourse in the trial, ulipristal acetate provided significant prevention of pregnancy, whereas levonorgestrel did not, the scientists state. Unlike levonorgestrel, ulipristal acetate is licensed for use beyond 72 hours and up to 120 hours, they state.
In looking at the two drugs, researchers note that the safety of levonorgestrel has been proven by its use by millions of women in a variety of formulations and doses, and so it can be made available without prescription. Although ulipristal acetate possibly could be made available from pharmacies and nurses, it cannot be made as easily accessible as levonorgestrel until there are more safety data, they note.
Progesterone-receptor modulators, including ulipristal acetate, given at high or repeated doses have an effect on endometrial histology and histochemistry that could theoretically impair implantation of a fertilized oocyte, note researchers.3,4 "Although an endometrial effect, and therefore an additional postovulatory mechanism of action, cannot be excluded, the dose of ulipristal acetate used in this trial was specifically titrated for emergency contraception on the basis of inhibition of ovulation and might be too low to inhibit implantation," they state.
Research demonstrates no decrease in pregnancies over time in women who have used a levonorgestrel emergency contraceptive pill,5,6 notes Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta. The more effective ulipristal acetate pill would be a positive improvement in the options clinicians can offer women after unprotected sex; however, the real problem is that women who need emergency contraception once are likely to need it multiple times in the course of a year, Hatcher notes.
"In my opinion, our entire approach to emergency contraception should shift from emergency contraceptive pills to emergency insertion of a copper or levonorgestrel intrauterine device," Hatcher states.