Pharmacology Update

Ulipristal Acetate Tablets (Ella™)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.

A new emergency contraceptive has been approved by the FDA that is effective up to 5 days after unprotected intercourse. Ulipristal acetate is a selective progesterone receptor modulator with partial agonist and partial antagonistic effects. It is licensed from Laboratoire HRA Pharma in France and marketed by Watson Pharma as Ella™.

Indications

Ulipristal is indicated for the prevention of pregnancy following unprotected intercourse or a known or suspected contraceptive failure.1

Dosage

One ulipristal tablet should be taken as soon as possible, within 120 hours of intercourse.1 It may be taken without regard to meals. Each tablet contains 30 mg of ulipristal acetate.

Potential Advantages

Ulipristal may be taken up to 5 days after intercourse compared to 3 days for levonorgestrel (Plan B One Step or Next Choice).

Potential Disadvantages

The most common adverse events are headache (18%-19%), nausea (12%-13%), abdominal pain (8%-15%), and dysmenorrhea (7%-13%).1 Inducers of CYP3A4 may decrease the effectiveness of ulipristal.

Comments

Ulipristal acetate is a selective progesterone receptor modulator. This group includes mifepristone (RU-486). The efficacy of ulipristal acetate was shown in two clinical studies. One was an open-label study and the other a single-blind comparative study.1-3 In the first study, ulipristal was taken 48-120 hours after unprotected intercourse. In the second, ulipristal was compared to levonorgestrel.2 The primary endpoint was pregnancy rate in subjects younger than 36 years of age. In the open-label trial, 1242 women were evaluated with a follow-up pregnancy rate of 2.2% (95% confidence interval, 1.5-3.2). This was a reduction of 60% from the expected rate of 5.5%.1,2 The efficacy appears to be maintained up to 120 hours after unprotected intercourse. The comparative study was a randomized non-inferiority trial compared to levonorgestrel.1,3 Women were randomized to ulipristal 30 mg or levonorgestrel 1.5 mg. In the efficacy-evaluable population (n = 1619) that received the emergency contraception within 72 hours, the pregnancy rate was 1.8% for ulipristal and 2.6% for levonorgestrel. In 203 women who received the contraceptive between 72 and 120 hours, there were no pregnancies in the ulipristal group and 3 in the levonorgestrel group. The study was not designed to demonstrate superiority of ulipristal over levonorgestrel. The most frequently reported adverse events were headache, nausea, dysmenorrhea, and abdominal pain. There was no clear difference in frequency of these adverse events between the two treatments. Onset of next menses after emergency contraception occurred a mean 2.1 days later than expected in the ulipristal group and 1.2 days earlier in the levonorgestrel group (P = 0.001).3

Clinical Implications

Currently, progestin-only emergency contraceptives recommended by the American College of Obstetrics and Gynecology (ACOG) include Plan B One Step and Next Choice.4 While the FDA-approved labeling indicates that these should be taken within 72 hours of unprotected intercourse, ACOG suggest that these are effective if taken within 5 days of unprotected intercourse. Ulipristal provides an alternative emergency contraceptive that is at least as effective as levonorgestrel.

References

1. Ella Prescribing Information. Morristown, NJ: Watson Pharma, Inc.; July 2010.

2. Fine P, et al. Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception. Obstet Gynecol 2010;115(2 Pt 1):257-263.

3. Glasier AF, et al. Ulipristal acetate versus levonorgestrel for emergency contraception. Lancet 2010;375: 555-562.

4. American College of Obstetrics and Gynecology. Available at: www.acog.org/departments/adolescentHealthCare/TeenCareToolKit/EmergContraception.pdf. Accessed Sept. 18, 2010.