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Cec Ceu Newproductreview Ellaone Oct 2009 PDF
Cec Ceu Newproductreview Ellaone Oct 2009 PDF
OF SEXUAL
& REPRODUCTIVE
HEALTHCARE
PRODUCT SUMMARY
Ulipristal acetate (ellaOne) is a selective progesterone receptor modulator (SPRM) licensed for emergency
contraception (EC) up to 120 hours after unprotected sexual intercourse (UPSI) or contraceptive failure.
Mechanism of Action
Primary mechanism is inhibition or delay of ovulation
Alterations to the endometrium may also contribute to efficacy
Efficacy
Efficacy has been demonstrated up to 120 hours after UPSI
Two randomised controlled trials have shown that ulipristal is at least as effective as progestogen-only EC
(POEC)
Pooled data suggest superior efficacy of ulipristal over POEC for intake within 24, 72 and 120 hours
Safety
Side effect profile similar to POEC
No serious reactions reported
Interactions
Efficacy may be reduced by drugs that induce liver enzymes or increase gastric pH
Potential interaction with progestogen-containing products but clinical significance unknown
Cost
Net price: 16.95 per pack of ellaOne (1 x 30 mg tablet)
Background
Emergency contraception (EC) is an important means of preventing unwanted pregnancy. In recent years,
two methods of EC have been available in the UK: oral progestogen-only emergency contraception (POEC)
containing levonorgestrel 1.5 mg (Levonelle, Bayer Schering Pharma) and the copper-bearing intrauterine
device (IUD). Levonelle is licensed to be given up to 72 hours after UPSI, although there is some evidence
of reducing efficacy with use after 72120 hours.1,2 The IUD can be inserted within 120 hours (5 days) of
UPSI or up to 5 days after the expected date of ovulation.3 Despite the high efficacy of the IUD and the
option to retain the device for ongoing contraception,3 oral EC is more commonly used because it is less
invasive and more easily accessible.
Ulipristal (ellaOne, HRA Pharma) is an oral emergency contraceptive newly launched onto the UK market
and licensed for use throughout Europe. This review evaluates the available evidence and summarises the
manufacturers recommendations for use of ulipristal. Wherever possible we have accessed published
literature; however, recent clinical trial data are currently only available as conference abstracts.
The review is intended to inform health professionals and is not a guidance document. Existing Faculty of
Sexual and Reproductive Healthcare (FSRH) guidance on EC3 will be updated to incorporate
recommendations on ulipristal in due course.
FSRH 2009 1
NEW PRODUCT REVIEW
What is ulipristal?
ellaOne consists of one tablet containing 30 mg micronised ulipristal acetate (Figure 1). Ulipristal acetate
(also known as CDB-2914 and VA2914) is a synthetic steroid derived from 19-norprogesterone (Figure 2). It
is a selective progesterone receptor modulator (SPRM), a class of compounds that exert tissue-selective full
agonist, antagonist or partial agonist effects at the progesterone receptor.4 The Summary of Product
Characteristics (SPC) indicates that ulipristal has antagonistic and partial agonistic effects.5
Ulipristal acetate
Mifepristone Progesterone
Figure 2 Comparison of chemical structures of progesterone, ulipristal acetate and mifepristone (figure
reproduced with the permission of Pharmacorama)
The first SPRM, mifepristone, is licensed for use in medical abortion and is also an effective emergency
contraceptive. Although a Cochrane review concluded that mifepristone is more effective than POEC up to
120 hours after UPSI,6 it has not been developed for this indication in the UK and is not licensed as EC
anywhere in Europe.
Ulipristal has been described as a second-generation SPRM. In vivo, ulipristal has much weaker
antiglucocorticoid activity than mifepristone as a result of differences in their active metabolites.710
2 FSRH 2009
NEW PRODUCT REVIEW
FSRH 2009 3
NEW PRODUCT REVIEW
Method Cost
ellaOne 16.95
Levonelle One-Step 13.83
Levonelle 1500 5.11
Intrauterine devices 8.0026.64
4 FSRH 2009
NEW PRODUCT REVIEW
References
1 von Hertzen H, Piaggio G, Ding J, Chen J, Song Si, Bartfai G, et al. Low dose mifepristone and two regimens of levonorgestrel for emergency
contraception: a WHO multicentre randomised trial. Lancet 2002; 360: 18031810.
2 Ngai SW, Fan S, Li S, Cheng L, Ding J, Jing X, et al. A randomized trial to compare 24h versus 12h double dose regimen of levonorgestrel for
emergency contraception. Hum Reprod 2004; 20: 307311.
3 Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit. Emergency contraception. J Fam Plann Reprod Health
Care 2006; 32: 121128. http://www.ffprhc.org.uk/admin/uploads/449_EmergencyContraceptionCEUguidance.pdf [Accessed 28 September
2009].
4 Chabbert-Buffet N, Meduri G, Bouchard P, Spitz IM. Selective progesterone receptor modulators and progesterone antagonists: mechanisms
of action and clinical applications. Hum Reprod Update 2005; 11: 293307.
5 HRA Pharm. ellaOne: Summary of Product Characteristics (SPC). 2009. http://ww.emc.medicines.org.uk [Accessed 28 September 2009].
6 Cheng L, Gulmezoglu AM, Van Look PFA. Interventions for emergency contraception. Cochrane Database Syst Rev 2008; 2: CD001324.
7 Reel JR, Hild-Petito S, Blye RP. Antiovulatory and postcoital antifertility activity of the antiprogestin CDB-2914 when administered as single,
multiple or continuous doses to rats. Contraception 1998; 58: 129136.
8 Hild SA, Reel JR, Hoffman LH, Blye RP. CDB-2914: anti-progestational/anti-glucorticoid profile and post-coital anti-fertility activity in rats and
rabbits. Hum Reprod 2000; 15: 822829.
9 Attardi BJ, Burgenson J, Hild SA, Reel JR, Blye RP. 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:
111123.
10 Attardi BJ, Burgenson J, Hild SA, Reel JR. 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 2004; 88: 277288.
11 Stratton P, Hartog B, Hajizadeh N, Merina M, Lee YJ, Nieman LK. A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits
folliculogenesis and endometrial differentiation in normally cycling women. Hum Reprod 2000; 15: 10921099.
12 Croxatto HB, Brache V, Cochon L, Jesam C, Salvatierra AM, Levy D, et al. The effects of immediate pre-ovulatory administration of 30 mg
ulipristal acetate on follicular rupture. Abstract presented at the 8th Congress of the European Society of Gynecology, Rome, Italy, 10-13
September 2009.
13 Stratton P, Levens ED, Hartog B, Piquion J, Wei Q, Merino M, et al. Endometrial effects of a single early luteal dose of the selective progesterone
receptor modulator CDB-2914. Fertil Steril 2009; 5 February (Epub ahead of print).
14 Passaro MD, Piquion J, Mullen N, Sutehrland D, Zhai S, Figg WD, et al. Luteal phase dose-response relationship of the antiprogestin CDB-
2914 in normally cycling women. Hum Reprod 2003; 18: 18201827.
15 Creinin MD, Schlaff WD, Archer DF, Wan L, Frezieres R, Thomas MR, et al. Progesterone receptor modulator for emergency contraception: a
randomized controlled trial. Obstet Gynecol 2006; 108: 10891097.
16 Ulmann A, Scherrer B, Mathe H, Gainer E, HRA Pharm. Meta-analysis demonstrating superiority of the selective progesterone receptor
modulator ulipristal acetate versus levonorgestrel for emergency contraception. Abstract and Poster Presentation presented at the 8th Congress
of the European Society of Gynecology, Rome, Italy, 1013 September 2009.
17 Fine P, Ginde S, Morfesisi J., Mathe H, Gainer. A multicentre trial of ulipristal acetate for late-intake emergency contraception. Abstract
presented at the 8th Congress of the European Society of Gynecology, Rome, Italy, 1013 September 2009.
18 Cameron S, Glasier A, Fine P, Mathe H, Gainer E. Ulipristal aceate compared to levonorgestrel for emergency contraception within five days
of unprotected intercourse: a randomised controlled trial. Abstract presented at the 8th Congress of the European Society of Gynecology,
Rome, Italy, 1013 September 2009.
19 Mansour D. EllaOne: a second-generation emergency contraceptive? J Fam Plann Reprod Health Care 2009; 35: 217218.
20 British National Formulary, Vol. 57. March 2009.
The FSRH Clinical Effectiveness Unit (CEU) has prepared the information given in this New Product Review. It is based on a
structured search and review of published evidence available at the date of preparation. This New Product Review has been
prepared as a service to FSRH members but is not a formal Faculty guidance document. It is not intended to be construed or to
serve as a standard of medical care. Such standards are determined on the basis of all clinical data available and are subject to
change as scientific knowledge advances. Members are welcome to reproduce this document by photocopying or other means,
in order to share the information with colleagues.
The CEU welcomes feedback on published documents, and will review all comments received and amend any significant errors.
The CEU is, however, unable to respond individually to all feedback.
Tel: +44 (0)141 232 8459 Fax: +44 (0)141 232 8448 E-mail: ceu.members@ggc.scot.nhs.uk
FSRH 2009 5
FACULTY
OF SEXUAL
& REPRODUCTIVE
Faculty of Sexual and Reproductive Healthcare
HEALTHCARE
of the Royal College of Obstetricians and
Gynaecologists
The Faculty
The Faculty of Family Planning and Reproductive Health Care (of the Royal College of Obstetricians
and Gynaecologists) was established on 26 March 1993. In 2007 the organisation changed its name
to the Faculty of Sexual and Reproductive Healthcare as this was more relevant to the current functions
of the specialty. The Faculty grants diplomas, certificates, fellowships and equivalent recognition of
specialist knowledge and skills in sexual and reproductive health care. As a body it promotes
conferences and lectures, provides a clinical advisory service and publishes the Journal of Family
Planning and Reproductive Health Care.
The Journal
The Journal of Family Planning and Reproductive Health Care publishes high-quality, peer reviewed
research and information relevant to clinical care, service delivery, training and education in the field of
contraception and reproductive/sexual health.
Visit the Faculty website at www.fsrh.org for further information about membership or Associate
membership and for details of how to subscribe to the Journal (subscriptions to this quarterly journal
include free online access).
The CEU
The Clinical Effectiveness Unit (CEU) provides a clinical enquiry service for Faculty members.
A standard process for developing evidence-based responses is used to respond to enquiries. The
CEU also publishes guidance documents, key statements and new product reviews.
Extra copies of this new product review may be available. For further information contact:
Sarah Monger, Commercial Manager, Keyways Publishing Ltd, part of the OLM Group.
Tel: +44 (0) 1243 816689. Fax: +44 (0) 1243 576456.
E-mail: sarah.monger@keywayspublishing.com