Ulipristal acetate for emergency contraception: postmarketing experience after use by more than 1 million women

doi:10.1016/j.contraception.2014.01.003

Contraception

Volume 89, Issue 5, May 2014, Pages 431-433

https://doi.org/10.1016/j.contraception.2014.01.003 Get rights and content

Abstract

Objective

To describe the safety of ulipristal acetate in emergency contraception.

Study design

Postmarketing pharmacovigilance data collection.

Results

A total of 553 women experienced 1049 adverse drug reactions. The most frequent (n,%) were pregnancies (282, 6.8%); nausea, abdominal pain and vomiting (139, 13.3%); headache, dizziness (67, 6.4%); and metrorrhagia, menses delay and breast symptoms (84, 8.0%). Including data from clinical trials, 376 pregnancies have been reported in total, 232 (62%) with a known outcome: 28 live births (29 newborns), 34 miscarriages, 151 induced abortions, 4 ectopics and 15 which are ongoing.

Conclusions

No safety concern emerges from a sizable database of reported adverse reactions following ulipristal acetate exposure among varying ethnicities and regions. Postapproval data confirm the safety profile described during the clinical trials.

Implications

Use of ulipristal acetate for emergency contraception in a variety of settings and among diverse populations indicate that it is safe and without unexpected or serious adverse events.

Introduction

The emergency contraceptive (EC) ulipristal acetate (UPA) 30 mg tablet was granted a Marketing Authorisation in the European Union in May 2009 and a New Drug Application approval in the United States in August 2010. UPA 30 mg tablet has been approved for EC in more than 70 countries and is currently marketed in 62 of them. The efficacy and safety profile of UPA from clinical studies has been described in the literature [1], [2], [3]. UPA is now recognized by many as the new gold standard in emergency contraception because of its high efficacy, especially when taken early after unprotected intercourse and close to ovulation. UPA for EC works by delaying or blocking ovulation for 5 days or more following unprotected intercourse, thereby preventing conception. Most women seek EC when they perceive themselves to be most at risk of pregnancy, which often is at midcycle [2]. At that point in the cycle, when ovulation is imminent, the other oral EC product, levonorgestrel is unable to prevent ovulation better than a placebo [4]. For an individual woman trying to avoid pregnancy, decreasing her pregnancy risk by two-thirds if UPA is taken within the first 24 hours after unprotected intercourse can be critical. Because UPA is still relatively new on the market, monitoring its safety profile is crucial. In order to gain a broader perspective on the safety of ella/ellaOne, postmarketing safety data have been collected in women exposed to the drug, with special interest in the outcomes of those who became pregnant.

Section snippets

Methods

In this article, we present safety data for UPA for emergency contraception (30 mg) gathered via the manufacturer's postmarketing surveillance activities since 2009, when it first became available in Europe. These data are collated from spontaneous reports received from health care professionals either directly or through the manufacturer's Web-based pregnancy registry http://www.hra-pregnancy-registry.com, review of the medical literature and reports received from regulatory authorities. In

Results

Internal sales data estimate that over 1,400,000 individual women have been exposed to UPA for emergency contraception worldwide. Between 1st October 2009 and 14th May 2013, 553 women from 23 countries reported 1049 suspected adverse drug reactions (ADRs). The most frequent events reported were pregnancies and gastrointestinal (nausea, abdominal pain, vomiting), nervous (headache, dizziness) and reproductive (metrorrhagia/genital haemorrhage, menses delay, breast symptoms) system disorders, as

Conclusions

Data from more than 5000 exposed women during clinical development of emergency contraception (EC) and uterine fibroid treatment and more than 1.4 million women in EC postmarketing surveillance indicate that the use of UPA 30 mg for EC appears safe. A sizable database of women exposed to the drug collected in a variety of regions and ethnic groups representative of Western populations shows no unexpected or severe adverse events. It is clinically important for health care professionals

References (7)

A. Glasier et al.
Ulipristal acetate versus levonorgestrel for emergency contraception: a randomized non-inferiority trial and meta-analysis
Lancet
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V. Brache et al.
Ulipristal acetate prevents ovulation more effectively than levonorgestrel — analysis of pooled data from three randomized trials of emergency contraception regimens
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M.J. Zinaman et al.
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(1996 Mar)

There are more references available in the full text version of this article.

Cited by (60)

Emergency contraception – A review
2023, European Journal of Obstetrics and Gynecology and Reproductive Biology
Emergency contraception (EC), or postcoital contraception, is a therapy aimed at preventing unintended pregnancy after an act of unprotected or under-protected sexual intercourse. Options include both emergency contraceptive pills (most commonly containing levonorgestrel or ulipristal acetate) and insertion of an intrauterine device. The aim of this paper is to summarize current evidence surrounding the use of emergency contraceptives and to present an evidence-based approach to EC provision.
Emergency contraception is a safe and effective option in preventing unwanted pregnancy, irrespective of age, weight, or breastfeeding status. Efforts should be made to increase their availability, as well as knowledge of these methods, both among patients and healthcare providers.
Society of Family Planning Clinical Recommendation: Emergency contraception
2023, Contraception
Emergency contraception (EC) refers to several contraceptive options that can be used within a few days after unprotected or under protected intercourse or sexual assault to reduce the risk of pregnancy. Current EC options available in the United States include the copper intrauterine device (IUD), levonorgestrel (LNG) 52 mg IUD, oral LNG (such as Plan B One-Step, My Way, Take Action), and oral ulipristal acetate (UPA) (ella). These clinical recommendations review the indications, effectiveness, safety, and side effects of emergency contraceptive methods; considerations for the use of EC by specific patient populations and in specific clinical circumstances and current barriers to emergency contraceptive access. Further research is needed to evaluate the effectiveness of LNG IUDs for emergency contraceptive use; address the effects of repeated use of UPA at different times in the same menstrual cycle; assess the impact on ovulation of initiating or reinitiating different regimens of regular hormonal contraception following UPA use; and elucidate effective emergency contraceptive pill options by body mass indices or weight.
Emergency contraception in the emergency department
2023, American Journal of Emergency Medicine
On June 24, 2022, the Supreme Court overturned Roe v. Wade, which will limit legal abortion in many areas of the U.S., making the need for effective emergency contraception even more critical.
This narrative review focuses on the approach to providing safe and effective emergency contraception in the emergency department (ED) with a focus on agents that are used in the U. S.; however, many of the agents discussed are also available and utilized in other countries.
Emergency contraception methods included in this review are, ulipristal, levonorgestrel, combined oral contraceptive pills, and copper intrauterine devices (IUDs).
The efficacy of products used for emergency contraception depend on patient and temporal factors. Emergency physicians must have an understanding of the optimal use of these agents to prevent unwanted pregnancy, particularly in the setting of restricted abortion access.
Emergency contraception and impact on abortion rates
2020, Best Practice and Research: Clinical Obstetrics and Gynaecology
Emergency contraception (EC) is a drug or a device that is taken after sexual intercourse to prevent unintended pregnancy. The most effective EC is the copper-bearing intrauterine device (Cu-IUD), but oral EC methods are more commonly used and include a single dose of either levonorgestrel (1.5 mg) or ulipristal acetate (30 mg). Although all EC methods are extremely safe, access to EC is often limited due to prevailing misconceptions over how EC works. Although EC can prevent unintended pregnancy for an individual woman, it has failed to make an impact on abortion rates at a population level. This may be because it is not used after every episode of unprotected sex and because existing oral EC methods are only effective if used before ovulation. Future strategies around EC should focus on maximising uptake of Cu-IUD, facilitating initiation of effective regular contraception after EC and developing a more effective oral EC.
Does ulipristal acetate emergency contraception (ella®) interfere with implantation?
2019, Contraception
Citation Excerpt :
No difference was observed in the percentage of cleaving embryos or the cleavage speed [6]. While there are no such studies on human embryos, data from both clinical trials and postmarketing surveillance of UPA-EC [7] show no increased risk of early pregnancy loss (miscarriage) or teratogenesis in women who conceive following exposure to UPA-EC. Thus, an effect of UPA 30 mg on embryo viability seems unlikely.
Ulipristal acetate (UPA) 30 mg (ella®, HRA-Pharma, Paris, France) acts as an emergency contraceptive (EC) by delaying ovulation. Because it is a selective progesterone receptor modulator, an additional effect on interfering with implantation has been suggested.
This review discusses the evidence for, and against, an anti-implantation effect of UPA-EC.
Primary research on the effect of UPA, at a relevant dose, on endometrium, implantation, efficacy and pregnancy outcome.
UPA-EC does not appear to have a direct effect on the embryo. Changes in endometrial histology are small and not consistent, varying among studies. While UPA-EC affects the profile of gene expression in human endometrium, the findings vary between studies, and it is not clear that these changes affect endometrial receptivity or prevent implantation. UPA at pharmacological concentrations does not appear to have any inhibitory effect on embryo attachment in in vitro systems of human endometrium. UPA-EC is not more effective at preventing pregnancy than chance alone if used after ovulation and does not increase miscarriage rates.
An anti-implantation effect of UPA is highly unlikely at the dose used for EC. Maintaining the warning on the FDA-approved label that “it may also work by preventing implantation to the uterus” might deter some women from using EC, leaving them no option to prevent unwanted pregnancy after unprotected sexual intercourse.
Ulipristal acetate compared to levonorgestrel emergency contraception among current oral contraceptive users: a cost-effectiveness analysis
2019, Contraception
To estimate the cost-effectiveness of ulipristal acetate (UPA) and levonorgestrel (LNG) emergency contraception (EC) on pregnancy prevention among combined oral contraceptive (COC) pill users with an extended pill-free interval. We accounted for the potential interaction of COCs and obesity on EC efficacy.
We built a decision-analytic model using TreeAge software to evaluate the optimal oral EC strategy in a hypothetical cohort of 100,000 twenty-five-year-old women midcycle with a prolonged "missed" pill episode (8–14 days). We used a 5-year time horizon and 3% discount rate. From a healthcare perspective, we obtained probabilities, utilities and costs inflated to 2018 dollars from the literature. We set the threshold for cost-effectiveness at a standard $100,000 per quality-adjusted life-year. We included the following clinical outcomes: number of protected cycles, unintended pregnancies, abortions, deliveries and costs.
We found that UPA was the optimal method of oral EC, as it resulted in 720 fewer unintended pregnancies, 736 fewer abortions and 80 fewer deliveries at a total cost savings of $50,323 and 79 additional adjusted life-years. UPA continued to be the optimal strategy even in the case of obesity or COCs impacting UPA efficacy, in which a COC interaction would have to change efficacy of UPA by 160% before LNG was the dominant strategy.
Our models found that UPA was the dominant choice of oral EC among COC users with a prolonged "missed" pill episode, regardless of body mass index or an adverse interaction of COCs on UPA.
Ulipristal acetate is the dominant choice of oral emergency contraception among combined oral contraceptive users.

View all citing articles on Scopus

^☆: Research funded by HRA Pharma.

^☆☆: Conflicts of interest: All authors are employed by HRA Pharma, which licenses ulipristal acetate for emergency contraception.

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Original research articleUlipristal acetate for emergency contraception: postmarketing experience after use by more than 1 million women☆,☆☆

Abstract

Objective

Study design

Results

Conclusions

Implications

Introduction

Section snippets

Methods

Results

Conclusions

Lancet

Contraception

Fertil Steril

Original research article
Ulipristal acetate for emergency contraception: postmarketing experience after use by more than 1 million women☆,☆☆