Ulipristal Acetate: Review of the Efficacy and Safety of a Newly Approved Agent for Emergency Contraception



      Emergency contraception (EC) is used to prevent unintended pregnancies. The current gold standard for oral EC is levonorgestrel (LNG) administered as a single 1.5-mg dose or in 2 doses of 0.75 mg separated by 12 hours. LNG has shown to be effective up to 72 hours after coitus. Ulipristal acetate (UPA) is a selective progesterone receptor modulator approved for EC use in the United States in August 2010. UPA is administered as a one-time, 30-mg dose within 120 hours of intercourse.


      The goal of this review was to provide a summary of the available literature on the use of UPA for EC.


      PubMed, Cochrane Library,, International Pharmaceutical Abstracts, EBSCO, and Iowa Drug Information Service were searched from February 2011 through September 2011 to identify relevant articles. Search terms included ulipristal acetate, CDB-2914, VA 2914, and emergency contraception.


      In an open-label study, UPA was effective in preventing pregnancy in 1241 women who presented for EC up to 120 hours (5 days) after unprotected intercourse, with an observed pregnancy rate of 2.1% (95% CI, 1.4%–3.1%) versus 5.5% (ie, the expected pregnancy rate without EC). The efficacy of UPA did not decrease significantly (P = 0.44) over time, with pregnancy rates at intervals between >48 and 72 hours at 2.3% (95% CI, 1.4%–3.8%), >72 and 96 hours at 2.1% (95% CI, 1.0%–4.1%), and >96 and 120 hours at 1.3% (95% CI, 0.1%–4.8%). In a single-blind, comparative noninferiority study of 1696 women, UPA was at least as effective as LNG when used within 72 hours for EC, with 15 pregnancies in the UPA group and 22 pregnancies in the LNG group (odds ratio = 0.68 [95% CI, 0.35–1.31]). In addition, UPA prevented significantly (P = 0.037) more pregnancies than LNG when used between 72 and 120 hours after unprotected intercourse, with 0 pregnancies in the UPA group and 3 pregnancies in the LNG group. In a meta-analysis, UPA prevented a greater percentage of pregnancies than LNG at intervals up to 24 hours (0.9% UPA vs 2.5% LNG; P = 0.035), up to 72 hours (1.4% UPA vs 2.2% LNG; P = 0.046), and up to 120 hours (1.3% UPA vs 2.2% LNG; P = 0.025). The most commonly (>10%) reported adverse events included headache, nausea, and abdominal pain. In addition, UPA delayed onset of menstruation by a mean of 2.1 to 2.8 days.


      Based on clinical trials, UPA seems to be a reasonably tolerable and effective method of EC when used within 120 hours of intercourse. UPA is at least as effective as LNG when used within the first 72 hours after unprotected intercourse. However, UPA may be more effective than LNG when used between 72 to 120 hours after unprotected intercourse, extending the window of opportunity for EC. UPA may provide a new option for women who require EC up to 5 days after unprotected intercourse.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit
        FFPRHC guidance: Emergency contraception.
        J Fam Plann Reprod Health Care. 2006; 32: 121-128
        • Wilcox A.J.
        • Weinberg C.R.
        • Baird D.D.
        Timing of sexual intercourse in relation to ovulation.
        N Engl J Med. 1995; 333: 1517-1521
        • Trussell J.
        • Stewart F.
        • Guest F.
        • Hatcher R.A.
        Emergency contractive pills: a simple proposal to reduce unintended pregnancies.
        Fam Plann Perspect. 1992; 24: 269-273
        • Trussell J.
        • Rodríguez G.
        • Ellertson C.
        New estimates of the effectiveness of the Yuzpe regimen of emergency contraception.
        Contraception. 1998; 57: 363-369
        • Orihuela P.A.
        Ulipristal: a progesterone receptor antagonist as an emergency contraceptive.
        Expert Rev Obstet Gynecol. 2010; 5: 13-17
        • Van Look P.F.
        • von Hertzen H.
        Emergency contraception.
        Br Med Bull. 1993; 49: 158-170
        • Cheng L.
        • Gülmezoglu A.
        • Oel C.
        • et al.
        Interventions for emergency contraception.
        Cochrane Database Syst Rev. 2004; 3 (CD001324)
        • Cheng L.
        • Gülmezoglu A.
        • Piaggi G.
        • et al.
        Interventions for emergency contraception.
        Cochrane Database Syst Rev. 2008; 2 (CD001324)
        • Hatcher R.A.
        • A N.
        The menstrual cycle.
        in: Hatcher R.A. Trussell J. Stewart F. Contraceptive Technology. 18th ed. Ardent Media, New York, NY2004
        • Gemzell-Danielsson K.
        Mechanism of action of emergency contraception.
        Contraception. 2010; 82: 404-409
        • Dickerson L.M.
        • Shrader S.P.
        • Diaz V.A.
        in: Dipiro J.T. Talbert R.L. Yee G.C. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. McGraw Medical, New York, NY2008: 1313-1327
        • Stanford J.
        • Mikolajczyk R.
        Mechanisms of action of intrauterine device: update and estimation of postfertilization effects.
        Am J Obstet Gynecol. 2002; 187: 1699-1708
        • Trussell J.
        • Leveque J.
        • Wysocki S.
        • et al.
        The economic value of contraception a comparison of 15 methods.
        Am J Public Health. 1995; 85: 494-503
        • Zhou L.
        • Xiao B.
        Emergency contraception with multi-load cu-375 SL IUD: a multicenter clinical trial.
        Contraception. 2001; 64: 107-112
        • World Health Organization (WHO)
        Selected Practice Recommendations for Contraceptive Use. 2nd ed. WHO, Geneva, Switzerland2004
        • The American College of Obstetricians and Gynecologists, Women's Health Care Physicians
        Emergency contraception.
        Obstet Gynecol. 2010; 115: 1100-1109
        • Centers for Disease Control and Prevention
        US medical eligibility criteria for contraceptive use (adapted from the World Health Organization medical eligibility criteria for contraceptive use, 4th ed).
        (Updated 2010) (Accessed March 1, 2011)
        • Grimes D.
        Intrauterine devices.
        in: Hatcher R.A. Trussell J. Nelson A.L. Contraceptive Technology. 18th ed. Ardent Media, New York, NY2004: 499-502
        • Morris J.M.
        • Van Wagenen G.
        Compounds interfering with ovum implantation and development: the role of estrogens.
        Am J Obstet Gynecol. 1966; 15: 804-815
        • Yuzpe A.A.
        • Thurlow H.J.
        • Ramzy I.
        • Leyshon J.I.
        Post coital contraception: a pilot study.
        J Reprod Med. 1974; 13: 53-58
        • WHO Task Force on Postovulatory Methods of Fertility Regulation
        Randomized controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception.
        Lancet. 1998; 352 (428–422)
        • Glasier A.
        • Cameron S.
        • Gainer E.
        • et al.
        Ulipristal acetate versus levonorgestrel for emergency contraception: a randomized non-inferiority trial and meta-analysis.
        Lancet. 2010; 375: 555-562
        • Gemzell-Danielsson K.
        • Meng C.X.
        Emergency contraception: potential role of ulipristal acetate.
        Int J Womens Health. 2010; 2: 53-61
        • Piaggio G.
        • von Hertzen H.
        • Grimes D.
        • Van Look P.
        • Task force on postovulatory methods of fertility regulation
        Timing of emergency contraception with levonorgestrel or the Yuzpe regimen.
        Lancet. 1999; 353: 721
        • Glasier A.
        Emergency postcoital contraception.
        N Engl J Med. 1997; 337: 1058-1064
        • Glasier A.
        • Thong K.J.
        • Dewar M.
        • et al.
        Mifepristone (RU486) compared with high dose estrogen and progestin for emergency postcoital contraception.
        N Engl J Med. 1992; 327: 1041-1044
        • Fine P.
        • Mathe H.
        • Ginde S.
        • et al.
        Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception.
        Obstet Gynecol. 2010; 115: 257-263
      1. Ella [package insert].
        Watson Pharmaceuticals, Morristown, NJAugust 2010 (Accessed March 12, 2011)
      2. Next Choice [package insert].
        Watson Laboratories, Corona, CalifDecember 2009 (Accessed March 12, 2011)
      3. Plan B [package insert].
        Duramed Pharmaceuticals, Pomona, CalifJuly 2009 (Accessed March 12, 2011)
      4. Plan B One-Step [package insert].
        Duramed Pharmaceuticals, Pomona, CAAugust 2009 (Accessed March 12, 2011)
        • Levens E.
        • Potlog-Nahari C.
        • Nieman L.
        • et al.
        CDB-2914 for uterine leiomyomata treatment: a randomized controlled trial.
        Obstet Gynecol. 2008; 111: 1129-1136
        • US Food and Drug Administration
        Ulipristal acetate: new drug review application 22-474.
        Center for Drug Evaluation and Research. 2009;
        • Creinin M.
        • Schlaff W.
        • Archer D.F.
        • et al.
        Progestin receptor modulator for emergency contraception: a randomized control trial.
        Obstet Gynecol. 2006; 108: 1089-1097
        • Wagner B.L.
        • Polio G.
        • Giangrande P.
        • et al.
        The novel progesterone receptor antagonist RTI 3021-3012 and RTI 3021-3022 exhibit complex glucocorticoid receptor activities: implications for the development of dissociated antiprogestins.
        Endocrinology. 1999; 140: 1449-1458
        • Attardi B.J.
        • Burgenson J.
        • Hild S.A.
        • Reel J.R.
        In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone.
        J Steroid Biochem Mol Biol. 2004; 88: 277-288
        • Attardi B.J.
        • Burgenson J.
        • Hild S.A.
        • et al.
        CDB-4124 and its putative monodemethylated metabolite, CDB-4453, are potent antiprogestins with reduced antiglucocorticoid activity: in vitro comparison to mifepristone and CDB-2914.
        Mol Cell Endocrinol. 2002; 188: 111-123
        • Blithe D.L.
        • Nieman L.K.
        • Blye R.P.
        • et al.
        Development of the selective progesterone receptor modulator CDB-2914 for clinical indications.
        Steroids. 2003; 68: 1013-1017
        • Cook C.E.
        • Raje P.
        • Lee D.Y.
        • Kepler J.A.
        Effect of 17alpha-(3-hydroxypropyl)-17beta-acetyl substituents pattern on the glucocorticoid and progestin receptor binding of 11beta-arylestra-4,9-dien-3-ones.
        Org Lett. 2001; 3: 1013-1016
        • Gainer E.E.
        • U A.
        Pharmacologic properties of CDB(VA)-2914.
        Steroids. 2003; 68: 1005-1011
        • Rao P.N.
        • Wang Z.
        • Cessac J.W.
        • et al.
        New 11beta-aryl-substituted steroids exhibit both progestational and antiprogestational activity.
        Steroids. 1998; 63: 523-530
        • Brache V.
        • Cochon L.
        • Jesam C.
        • et al.
        Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture.
        Hum Reprod. 2010; 25: 2256-2263
        • Stratton P.
        • Hartog B.
        • Hajizadeh N.
        • et al.
        A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women.
        Hum Reprod. 2000; 15: 1092-1099
        • Stratton P.
        • Levens E.D.
        • Hartog B.
        • et al.
        Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB-2914.
        Fertil Steril. 2010; 93: 2035-2041
      5. Red Book Online (internet database).
        (Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically) (Accessed July 20, 2011)