Options now eyed in emergency contraception

Clinicians are familiar with use of dedicated emergency contraceptive (EC) products such as Plan B One-Step (Teva Pharmaceuticals USA) and Next Choice (Watson Pharmaceuticals), as well as the EC use of the copper T380A intrauterine device (ParaGard IUD, Duramed Pharmaceuticals). Now new options are now being eyed for potential use in EC.

Scientists are looking at meloxicam, a cyclooxygenase-2 (COX-2) inhibitor, as a possible emergency contraceptive. In a recent study, a five-day course of oral meloxicam administered around the time of ovulation in adult cynomolgus monkeys reduced the rate of oocyte release without alteration of reproductive hormones or menstrual cycle length.1

What characteristics of meloxicam make it a potential candidate for use in emergency contraceptive? Meloxicam was shown to specifically block ovulation, so this is a new site of action for emergency contraceptives, says Diane Duffy, PhD, associate professor at Eastern Virginia Medical School, Norfolk, and lead author of the current study. Meloxicam is not a hormone, so it will not have the hormonal side effects of current emergency contraceptive pills, Duffy notes.

The research group CONRAD, in partnership with the Hewlett Foundation, is looking into potential use of meloxicam. Results from two studies suggest it might improve the efficacy of levonorgestrel (LNG) when used for emergency contraception, and it even might be effective for EC when used alone.2,3 LNG is the primary product used for emergency contraception; meloxicam might expand LNG's window of effectiveness and have fewer side effects.

What is the next step in research for meloxicam? Duffy's research group would like to determine if other essential reproductive events, in addition to ovulation, are prevented by meloxicam. If so, this would make meloxicam even more effective as a contraceptive, she notes. The team also would like to conduct a contraceptive trial to determine if meloxicam can effectively operate as a traditional contraceptive, says Duffy.

Women in European countries now have another option in emergency contraception with the European Commission's 2009 marketing authorization of ellaOne (ulipristal acetate, HRA Pharma, Paris). In a Phase II randomized double-blinded trial of women seeking EC within 72 hours of unprotected sex, pregnancies occurred in seven of 775 ulipristal users [0.9%, 95% confidence interval (CI) 0.2-1.6] and 13 of 774 levonorgestrel users (1.7%, 95% CI 0.8-2.6).4

Data suggest ulipristal is well tolerated and effective when administered to women 48-120 hours following unprotected sex.5 Results of a randomized trial indicate efficacy up to 120 hours with a trend toward greater efficacy in the ulipristal group vs. levonorgestrel.6 The drug, a selective progesterone receptor modulator, is licensed as ellaOne for emergency contraception up to 120 hours after unprotected sexual intercourse or contraceptive failure. Its primary mechanism of action is inhibition or delay of ovulation; alterations to the endometrium also might contribute to its efficacy.7 It is packaged as a single 30 mg tablet.

Research regarding ulipristal is under way in the United States; a second U.S. Phase III trial for ulipristal has been completed, says Christina Aplington, an HRA Pharma spokeswoman.

Will the company seek U.S. approval of ellaOne? "HRA Pharma would like to obtain approval in the United States for ellaOne; however the company does not communicate any information about the timing of this process," she states.

References

  1. Hester KE, Harper MJ, Duffy DM. Oral administration of the cyclooxygenase-2 (COX-2) inhibitor meloxicam blocks ovulation in non-human primates when administered to simulate emergency contraception. Hum Reprod 2009; 25:360-367.
  2. Massai MR, Forcelledo ML, Brache V, et al. Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study. Hum Reprod 2007; 22:434-439.
  3. Jesam C, Salvatierra AM, Schwartz JL, et al. Suppression of follicular rupture with meloxicam, a cyclooxygenase-2 inhibitor: Potential for emergency contraception. Hum Reprod 2010; 25:368-373.
  4. Creinin MD, Schlaff WD, Archer DF, et al. Progesterone receptor modulator for emergency contraception: A randomized controlled trial. Obstet Gynecol 2006; 108:1,089-1,097
  5. Fine P, Ginde S, Morfesisi J, et al. A multicentre trial of ulipristal acetate for late-intake emergency contraception. Presented at the Eighth Congress of the European Society of Gynecology. Rome; September 2009.
  6. Cameron S, Glasier A, Fine P, et al. Ulipristal acetate compared to levonorgestrel for emergency contraception within five days of unprotected intercourse: A randomised controlled trial. Presented at the 8th Congress of the European Society of Gynecology. Rome; September 2009.
  7. Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit. New product review (October 2009). Ulipristal acetate (ellaOne). Accessed at www.ffprhc.org.uk/admin.