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Ulipristal Acetate for Emergency Contraception

ARTICLE in ANNALS OF PHARMACOTHERAPY JUNE 2011
Impact Factor: 2.06 DOI: 10.1345/aph.1P704 Source: PubMed

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ARTICLES
New Drug Approvals

Ulipristal Acetate for Emergency Contraception

Sara E Snow, Stephanie N Melillo, and Courtney I Jarvis

See also page 813.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety
of data of ulipristal acetate, a new emergency contraceptive approved for use up
to 120 hours after unprotected intercourse.

n unintended pregnancy is defined

as either a mistimed or unwanted
DATA SOURCES: Articles pertaining to the topic were identified and reviewed
pregnancy at the time of conception. Unthrough searches of PubMed (1994-March 2011) and clinicaltrials.gov, using the
key terms ulipristal and CDB-2914. Ella approval documents were obtained and
intended pregnancies are often associatreviewed from Drugs@FDA on the Food and Drug Administration (FDA) Web
ed with underuse of prenatal care, insite.
creased risk of low-birth weight babies,
1
STUDY
SELECTION AND DATA EXTRACTION: All published data and FDA approval
and lower likelihood of breast feeding.
documents examining pharmacologic, pharmacokinetic, and clinical studies
Each year, 800,000-900,000 adolescent
related to ulipristal acetate as an emergency contraceptive were evaluated.
females become pregnant and more than
Selected studies included 3 randomized trials and 1 meta-analysis.
80% of pregnancies in women younger
DATA SYNTHESIS: Ulipristal acetate is a progesterone agonist/antagonist
than 20 years of age are unintended.2
emergency contraceptive approved for the prevention of pregnancy to be taken
Due to poor use of effective methods of
as soon as possible, within 120 hours after unprotected intercourse or a known or
suspected contraceptive failure. Based upon results of the Phase 3 clinical trials
contraception, the US demonstrates one
used to obtain approval, ulipristal acetate administration was at least as effective
of the highest rates of unintended pregas levonorgestrel in the reduction of pregnancy rate when studied alone after
1
nancy among developed countries. The
unprotected intercourse and when taken up to 120 hours after unprotected
timely use of emergency contraception
intercourse. Commonly reported adverse effects associated with ulipristal acetate
(EC) could reduce the risk of pregnancy
in trials included headache, breast tenderness, nausea, and abdominal pain.
by as much as 89-99% and could preCONCLUSIONS: Ulipristal acetate is effective as an emergency contraceptive for
vent as many as 1.5 million pregnancies
up to 120 hours after unprotected intercourse. Because ulipristal is available only
via prescription, it may be covered by insurance. However, the additional factors
each year.3 EC comprises several pharof
travel expenses and time to make and attend a physician appointment must be
maceutical products that can be used by
taken into account when considering use of ulipristal as an emergency
a woman to prevent pregnancy when she
contraceptive. Due to the similarity of its structure to mifepristone, controversy
has had unprotected or inadequately proregarding ulipristals mechanism of action has arisen.
tected sexual intercourse within the last
KEY WORDS: CDB-2914, ella, emergency contraception, ulipristal acetate.
few hours to days, is afraid she may get
Ann Pharmacother 2011;45:780-6.
pregnant, and wants to prevent it.4
Published Online, 10 Jun 2011, theannals.com, DOI 10.1345/aph.1P704
Previously, the Food and Drug Administration (FDA) has recognized only
progestin pills and combined oral contratwo 0.75-mg tablets of levonorgestrel available by preceptives with levonorgestrel or norgestrel for use as EC.3
scription, with the conversion to over-the-counter (OTC)
Plan B was originally approved by the FDA in 1999 as
status occurring in August 2006.5 A generic EC, Next
Choice, containing two 0.75-mg tablets of levonorgestrel,
Author information provided at end of text.
became available in 2009 from Watson Pharmaceuticals.1,5

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In July 2009, Teva Pharmaceuticals released Plan B OneStep, containing 1.5 mg levonorgestrel, which is now
available OTC for patients 17 years of age and older and as
prescription for girls younger than 17.1
On August 13, 2010, HRA Pharma obtained approval for
the use of ulipristal acetate (ella) 30-mg tablets for the prevention of pregnancy following unprotected intercourse or a
known or suspected contraceptive failure. As ulipristal acetate was unavailable in any drug product in the US, it obtained approval as a new molecular entity. Ella potentially extends the availability of FDA-approved EC from 3 days (72
hours) after unprotected intercourse for currently approved
levonorgestrel-based EC products to 5 days (120 hours). Under the proprietary name of ellaOne, ulipristal gained approval from the European Medicines Agency (EMA) in May
2009 and is currently marketed in over 20 countries.6
Data Sources and Selection
Relevant articles were identified and reviewed through
searches of PubMed (1994-March 2011) and clinicaltrials.
gov, using the key terms ulipristal and CDB-2914. Ella approval documents were obtained and reviewed from
Drugs@FDA on the FDA Web site.
Pharmacology and Pharmacokinetics

midfollicular phase, inhibition of folliculogenesis and reduction of estradiol concentration occur. When administering ulipristal acetate at the time of the luteinizing hormone
(LH) peak, follicular rupture is delayed by 5-9 days. Endometrial maturation is not significantly delayed upon dosing of ulipristal acetate in the early luteal phase, but endometrial thickness decreases by 0.6 2.2 mm.
Ulipristal acetate demonstrates high binding (>94%) to
plasma proteins, including high-density lipoprotein, -acid
glycoprotein, and nonesterified fatty acid. It undergoes metabolism to mono-demethylated and di-demethylated
metabolites, with the mono-demethylated metabolite being
pharmacologically active.6
Although no drug interaction studies have been conducted in vivo for ulipristal acetate, in vitro data indicate
that it is predominantly metabolized by CYP3A4.7 Therefore, drugs or herbal products that induce the CYP3A4
isoenzyme (eg, barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxacarbazepine, phenytoin, rifampin,
St. Johns wort, and topiramate) may decrease concentrations and the effectiveness of ulipristal acetate. Plasma
concentrations of ulipristal acetate may be increased by
medications such as itraconazole or ketoconazole, which
are CYP3A4 inhibitors.7 In vitro data demonstrate that
ulipristal acetate neither induces nor inhibits the activity of
CYP450 enzymes.
Food increases the extent of absorption of ulipristal acetate and its mono-demethylated metabolite as indicated
by a 20-25% higher area under the curve compared to fasting conditions. However, Phase 3 studies were conducted
without restriction for food, so ulipristal acetate can be administered to patients regardless of a meal. To our knowledge, no studies for ulipristal acetate have been conducted
in patients with hepatic or renal dysfunction to date.6 Further pharmacologic and pharmacokinetic parameters are
described in Table 1.

Ulipristal acetate is a selective progesterone receptor

modulator with both antagonistic and partial agonistic effects.7 It binds the human progesterone receptor and prevents progesterone from occupying the receptor. Although
no single mechanism of action has been established for
EC, the action of levonorgestrel as an EC appears to be
similar to that of ulipristal acetate in that it is thought to inhibit ovulation and fertilization. Alteration of the endometrium to inhibit implantation is a potential mechanism, but the changes may not be sufficient to prevent implantation.8 Ulipristal acetate is indicated to be taken within
Clinical Trials
120 hours (5 days) of unprotected intercourse, whereas
levonorgestrel is indicated within 72 hours (3 days), but
Four11-14 major trials have been conducted to evaluate
has been shown to be effective when the first dose is taken
the safety and efficacy of ulipristal acetate as EC, 312-14 of
up to 5 days after intercourse Both agents are thought to be
which have been published. The randomized double-blind
effective only before pregnancy is established.
Ulipristal acetate demonstrates structural similarity to mifepristone in that both are 19-norprogesterone derivatives with 11-aryl substitutions (Figure 1).9 Mifepristone was the first
progesterone receptor antagonist and has been
in clinical use for over 25 years. It is used as a
single dose for the termination of pregnancy.10
The pharmacodynamics associated with
ulipristal acetate depend upon the timing of its
administration in the menstrual cycle.7 Upon
Figure 1. Structural similarities between ulipristal acetate and mifepristone.9
administration of ulipristal acetate during the
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SE Snow et al.

Phase 2/3 extension study comparing 2 doses of ulipristal

acetate (10 mg and 50 mg) has not yet been published. An
unmicronized 50-mg gelatin capsule was chosen for the
Phase 2/3 studies based on results from previous pharmacodynamic studies; however, commercialization of this
formulation was not viable.11 Based on the results of a
pharmacokinetic bridging study with 3 different formulations and an indirect pharmacokinetic comparison with
data on the absorption of the 50-mg capsule, a 30-mg
tablet was chosen to be evaluated in the pivotal Phase 3
registration trials.11 Information pertaining to the published
clinical trials is described in detail below.
Creinin et al.12 conducted a Phase 2/3 randomized, double-blind, noninferiority trial to evaluate the safety and efficacy of ulipristal acetate (single dose of 50 mg) compared
to levonorgestrel (2 doses of 0.75 mg taken 12 hours apart)
within 72 hours of unprotected intercourse. The study was
initiated before data demonstrating the efficacy of levonorgestrel as a single-dose regimen and beyond 72 hours
from sexual intercourse were available. The study was performed in 1672 healthy women, at least 18 years of age,
seeking EC within 72 hours of unprotected intercourse or
contraceptive failure. Women pregnant at screening or enrollment were excluded from the study. The primary outcome of pregnancy was established via a positive highsensitivity urine pregnancy test at follow-up (5-7 days after
the expected onset of the next menstrual period), and confirmed by quantitative serum -human chorionic gonadotropin (hCG). The study was designed as a noninferiority trial to test the hypothesis that ulipristal acetate has a
pregnancy rate no greater than that of levonorgestrel with a
noninferiority margin of 2%. Daily diaries were used from
the time of study drug administration through the next
menses to record adverse effects and sexual activity. Study
participants were primarily young (mean age 24.3 years),
white, single women. As illustrated in Table 2, 7 pregnancies occurred in the ulipristal acetate group (n = 775; 0.9%;

Table 1. Summary of Ulipristal and Mono-Demethylated

Metabolites Pharmacologic/Pharmacokinetic Profile7,10
Parameter

Ulipristal

Mono-Demethylated Metabolite
27 (6.9)

Half-life (h)

32 (6.3)

Cmax (ng/mL)

176 (89)

69 (26)

AUC0-t (ng-h/mL)

548 (259)

240 (59)

AUC0- (ng-h/mL)
tmax (h)

556 (260)

246 (59)

0.9 (0.5-2.0)

1.00 (0.8-2.0)

Ulipristal/chemical 17-acetoxy-11-(4-N,N-dimethylaminophenyl)19-norpregna-4,9-diene-3,20-dione
name
Molecular weight

475.6

Molecular formula

C30H37NO4

AUC = area under the curve; Cmax = maximum concentration; tmax =

time to maximum concentration.

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95% CI 0.2 to 1.6) and 13 in the levonorgestrel group (n =

774; 1.7%; 95% CI 0.8 to 2.6) in the efficacy evaluable
population. This population did not include those lost to
follow-up, 5 women with pretreatment pregnancy, and 24
women who used additional EC during the treatment cycle. The difference in number of pregnancies between
treatment groups was statistically noninferior (p < 0.001).
Based on the estimated cycle day of unprotected intercourse, 85% and 69% of anticipated pregnancies were
averted.12 Efficacy was also evaluated in the modified intent-to-treat population (mITT) population, which included
all women who were randomized and for whom a pregnancy outcome was known. In the mITT population, 12
pregnancies were observed among ulipristal acetate users
(n = 792; 1.5%; 95% CI 0.7 to 2.4), and 14 among levonorgestrel users (n = 786; 1.8%; 95% CI 0.9 to 2.7%), also
a statistically noninferior difference (p = 0.003).
Fine et al.13 conducted a Phase 3, prospective, open-label study to evaluate the safety and efficacy of a single
dose of ulipristal acetate 30 mg in women at least 18 years
of age presenting to Planned Parenthood clinics 48-120
hours after unprotected intercourse. Exclusion criteria included pregnancy, breastfeeding, intrauterine devices, tubal
ligation, or partner vasectomy, and uncertainty about recent
menstrual history. Daily diaries were used and pregnancy
status was determined via a high-sensitivity urinary hCG
test and return of menses. Up to 3 visits were scheduled
during the study, beginning with an initiation visit during
which a high-sensitivity urine pregnancy test was performed and a blood sample was obtained. The first followup visit was conducted 5-7 days after expected onset of
menses and included a second pregnancy test. A second
follow-up visit occurred only if the previous pregnancy test
result was positive or if the test result was negative but
menses had not occurred. Subjects were mostly healthy,
young (mean age 24.4 years), white, healthy weight to
overweight women. The primary efficacy endpoint of
pregnancy rate was evaluated in the mITT population,
which excluded women lost to follow-up and those 36
years of age and older. When taken 48-120 hours after unprotected intercourse, ulipristal acetate administration resulted in a statistically significant reduction in the pregnancy rate, from an expected rate of 5.5%15 to an observed rate
of 2.2%. While the efficacy of ulipristal acetate did not appear to decrease, the sample sizes for the individual time
intervals of 72-96 and 96-120 hours were not large enough
to determine statistical significance.
In a Phase 3 randomized, single-blind, multicenter noninferiority trial, Glasier et al.14 compared the safety and efficacy of ulipristal acetate 30 mg with that of levonorgestrel 1.5 mg in women (at least 16 years of age in the
UK and 18 years of age in the US) with regular menstrual
cycles requesting EC within 5 days of unprotected sexual
intercourse. Women were excluded if they were pregnant,

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Ulipristal Acetate for Emergency Contraception

breastfeeding, sterilized (or their partner was sterilized), fitted with an intrauterine device, or taking hormonal contraception. Daily diaries were used to record sexual intercourse, contraceptive use, vaginal bleeding, concomitant
medication, and adverse events. Follow-up was conducted
5-7 days after expected menses. The primary efficacy endpoint was the pregnancy rate in women who received EC
within 72 hours of unprotected intercourse. The rate of
pregnancy in women who received EC within 120 hours
was analyzed as a secondary endpoint. This study was not
powered to demonstrate superiority. Participants were primarily young (mean age 24.5 years in the ulipristal acetate
group and 24.9 years in the levonorgestrel group), healthy,
white women. The efficacy-evaluable population, which
excluded women lost to follow-up, those over 35 years,
women with unknown follow-up pregnancy status, and
those who had reenrolled in the study, included 1696 women who received EC within 72 hours of sexual intercourse
(ulipristal acetate, n = 844; levonorgestrel, n = 852). A total
of 15 pregnancies in the ulipristal acetate (1.8%; 95% CI

1.0 to 3.0) and 22 in the levonorgestrel group (2.6%; 95%

CI 0.35 to 1.31) were observed in this population. Significantly more pregnancies were prevented in the ulipristal
acetate group than in the levonorgestrel group in women
who received EC between 72 and 120 hours after sexual
intercourse (p = 0.037).12 Fifty pregnancies occurred in the
ulipristal acetate group and 30 in the levonorgestrel group
in the ITT population.
Glasier et al.14 also conducted a meta-analysis of the
combined data from the efficacy evaluable populations in
their trial and the Creinin et al. trial.12 The rate of pregnancy was significantly lower in the ulipristal acetate group
compared to the levonorgestrel group when EC was taken
within 24 hours (OR 0.35; 95% CI 0.11 to 0.93), 72 hours
(OR 0.58; 95% CI 0.33 to 0.99), or 120 hours (OR 0.55;
95% CI 0.32 to 0.93) after sexual intercourse (p < 0.05 for
all). The validity of these data is questionable as the metaanalysis included only 2 trials, both with noninferiority
designs and different dosing/formulations and populations.

Table 2. Efficacy of Ulipristal Acetate in Clinical Trials

According to Time from Unprotected Sexual Intercourse to Administration of ECa
Outcomes

Reference

Treatment
12

Creinin (2006)

Ulipristal acetate

Total
0-24 h

Levonorgestrel

Glasier (2010)14

Ulipristal acetate

Ulipristal acetate

775

0.9 (0.2-1.6)

85 (68-93)

273

NR

100 (NE)

268

NR

57 (6-81)

>48-72 h

234

NR

93 (52-99)

774

13

263

Total

1.7 (0.8-2.6)

69 (46-82)

NR

71 (28-89)

>24-48 h

298

NR

81 (42-94)

>48-72 h

213

NR

50 (0-77)
62.3 (41.9-75.6)

1241

26

2.1 (1.4-3.1)

48 to 72 h

693

16

2.3 (1.4-3.8)

61.9 (36.3-77.2)

>72-96 h

390

2.1 (1.0-4.1)

57.9 (14.6-79.2)

>96 to 120 h

158

1.3 (0.1-4.8)

75.0 (6.2-93.3)

Total (0-120 h)

941

15

1.6

NR

0-24 h

312

1.6

NR

25-48 h

329

2.1

NR

49-72 h

203

1.5

NR

73-96 h

63

NR

NR

Total (0-120 h)

34

958

25

2.6

NR

0-24 h

337

10

3.0

NR

25-48 h

319

2.2

NR

49-72 h

196

2.6

NR

73-96 h

73

2.7

NR

97-120 h

33

3.0

NR

97-120 h
Levonorgestrel

Pregnancy
Rate, %
(95% CI)

>24-48 h

0-24 h

Fine (2010)13

Pregnancies
Averted,
% (95% CI)

Pregnancies,
n

Treatment,
n

Total

EC = emergency contraception; NE = not estimable; NR = not reported.

Efficacy evaluable population.

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Adverse Effects
Seven serious adverse events (SAEs) were observed in
the Phase 2/3 and Phase 3 trials.11-14 With the exception of a
report of dizziness in the Glasier et al. trial, which was identified as possibly related, all other SAEs were determined
by the investigator to be unrelated to ulipristal acetate use.11
In a pooled ITT population including subjects receiving
ulipristal acetate in the 3 published trials,12-14 the most commonly reported adverse events (Table 3) included headache
(17%; n = 3412), breast tenderness (16%; n = 775), nausea
(14.9%; n = 3412), and abdominal pain (12.8%; n = 3412).
Those most common in subjects who received levonorgestrel were headache (23%; n = 1891), abdominal pain
(17.5%; n = 1891), fatigue (17.5%; n = 1891), and nausea
(16.5%; n = 1891). Alterations in menses onset were also reported, as subjects in the pooled Phase 3 population who did
not become pregnant reported a mean change of 2.5 days
(9.4 SD) in average cycle length.11

similar products for coverage by Medicaid.2 Plan B OneStep and Next Choice are available as OTC products and,
as such, are not covered by private insurance for women
aged 18 years and older. Because ulipristal acetate is available only through prescription, the time and money for a
physicians appointment, as well as the time and transportation required to travel to the office or clinic, present
potential hurdles to it being widely used as EC.2 Another
pricing consideration associated with ulipristal acetate is
the cost of the pregnancy test required prior to administration of the drug. However, depending upon the individuals
insurance plan, ulipristal acetate may be covered, unlike
Plan B One-Step and Next Choice.2 For women without
insurance, ulipristal acetate can be obtained via an online
prescription and shipped for next-day delivery with an approximate cost of $77.16 Plan B One-Step and Next Choice
can be obtained OTC at a local pharmacy by women 17
years of age and older and as prescription for girls younger
than 17 for prices ranging from $35 to $60, depending on
the pharmacy.

Dosage and Formulary Considerations

The licensed dose of ella consists of 1 tablet of ulipristal
acetate 30 mg, taken as soon as possible, within 120 hours
(5 days) of unprotected sexual intercourse or contraceptive
failure.7 The drug must be obtained via prescription and
can be administered at any point during the menstrual cycle, without regard to meals. If vomiting occurs within 3
hours after the dose, it should be repeated. Pregnancy
should be excluded prior to its administration.
Currently, women with state-funded health insurance for
EC services require a prescription for levonorgestrel or

Summary
Based on results of the clinical trials summarized here,
ulipristal acetate administration resulted in a statistically
significant reduction in pregnancy rate after unprotected
intercourse and prevented a significantly larger number of
pregnancies than levonorgestrel when taken up to 120
hours after unprotected intercourse. Commonly reported
adverse effects associated with ulipristal acetate in these
trials included headache, breast tenderness, nausea, and abdominal pain.

Table 3. Safety of Ulipristal Acetate in Clinical Trialsa

Adverse Reactions

Creinin(2006)12
Levonorgestrel
Ulipristal Acetate
(n = 774)
(n = 775)

Fine (2010)13
Ulipristal Acetate
(n = 1533)

Glasier (2010)14
Levonorgestrel
Ulipristal Acetate
(n = 1117)
(n = 1104)

Abdominal painb

27

31

6.8

10.8

8.4

Back pain

NR

NR

NR

2.4

3.2
NR

Bleeding

NR

NR

Breast tenderness

15

16

NR

NR

NR

Diarrhea

11

12

NR

NR

NR

Dizziness

18

20

3.5

4.9

5.2

Dysmenorrhea

NR

NR

4.1

14.3

12.9

Fatigue

37

37

3.4

3.9

5.5

Headache

29

29

9.3

18.9

19.3

Nausea

24

29c

9.2

11.3

12.8

Spotting

NR

NR

NR

Vomiting

NR

NR

NR

NR = not reported.
a
Data are percentage in intent-to-treat population.
b
Upper, lower, and general abdominal pain included.
c
p < 0.05.

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Ulipristal Acetate for Emergency Contraception

As ulipristal acetate demonstrates structural similarity to

mifepristone, which when administered in a single dose
terminates pregnancy, much debate regarding the potential
mechanism of action of ulipristal acetate continues to occur among various parties, primarily on the basis of ethical
and religious concerns. This controversy also stems from
the fact that the primary mechanism of action of ulipristal
acetate has not been clearly defined, as well as the fact that
pregnancy must be excluded prior to its administration. As
a result of these factors, certain groups could make the argument that ulipristal acetate could be used to terminate
pregnancy. However, while the drug has been shown to be
effective in preventing pregnancy during the 5 days (120
hours) between unprotected intercourse and implantation
of a fertilized egg, it is thought to be ineffective after implantation of a fertilized egg and therefore presents no increased risk to an established pregnancy or harm to a developing embryo.8

11. FDA: Reproductive Health Drugs Advisory Committee: Rockville, MD:

Food and Drug Administration; 2010. Briefing document for ulipristal
acetate; 2010 Jun 17. www.fda.gov/downloads/AdvisoryCommittees/
CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisory
Committee/UCM215510.pdf (accessed 2010 Nov 2).
12. Creinin MD, Schlaff W, Archer DF, et al. Progesterone receptor modulator for emergency contraception: a randomized controlled trial. Obstet
Gynecol 2006;108:1089-97.
DOI 10.1097/01.AOG.0000239440.02284.45
13. Fine P, Math H, Ginde S, Cullins V, Morfesis J, Gainer E. Ulipristal acetate taken 48-120 h after intercourse for emergency contraception. Obstet Gynecol 2010;115:257-63. DOI 10.1097/AOG.0b013e3181c8e2aa
14. Glasier AF, Cameron ST, Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet 2010;375:555-62.
DOI 10.1016/S0140-6736(10)60101-8
15. Trussell J, Rodriguez G, Ellertson C. New estimates of the effectiveness
of the Yuzpe regimen of emergency contraception. Contraception 1998;
57:363-9. DOI 10.1016/S0010-7824(98)00042-0
16. Reproductive Health Technologies Project. FDA approved emergency
contraceptive products currently on the US market. Dec 2010. www.rhtp.
org/contraception/emergency/documents/FDAApprovedEmergency
ContraceptiveChartDecember2010-PRINTABLE.pdf (accessed 2011
Mar 25).

Sara E Snow PharmD MBA, Post-Doctoral Regulatory Affairs/Drug

Safety and Risk Management Fellow, Biogen Idec/Massachusetts
College of Pharmacy and Health Sciences, School of Pharmacy,
Worcester, Manchester, MA
Stephanie N Melillo PharmD, Post-Doctoral Regulatory Affairs/Drug
Safety and Risk Management Fellow, Biogen Idec/Massachusetts
College of Pharmacy and Health Sciences, School of Pharmacy,
Worcester, Manchester
Courtney I Jarvis PharmD, Associate Professor of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences,
School of Pharmacy, Worcester, Manchester
Correspondence: Dr. Snow, sarasnow23@gmail.com
Reprints/Online Access: www.theannals.com/cgi/reprint/aph.1P704

Conflict of interest: Authors reported none

References
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Pharm Assoc 2010;50:604-12. DOI 10.1331/JAPhA.2010.09195
2. Pitts SAB, Emans SJ. Controversies in contraception. Curr Opin Pediatr
2008;20:383-9. DOI 10.1097/MOP.0b013e328305e13f
3. Conard LA, Gold MA. Emergency contraception. Adolesc Med Clin
2005;16:585-602. DOI 10.1016/j.admecli.2005.06.001
4. Croxatto HB, Fernandez SD. Emergency contraceptiona human rights
issue. Best Pract Res Clin Obstet Gynaecol 2006;20:311-22.
DOI 10.1016/j.bpobgyn.2005.11.003
5. Drugs@FDA. Levonorgestrel (levonorgestrel) overview. www.accessdata.
fda.gov/scripts/cder/drugsatfda/indexcfm?fuseaction=Search.Overview&
DrugName=LEVONORGESTREL (accessed 2010 Oct 18).
6. Monroe S. Application number 22- 474 summary review. CDER. 2010
Aug. 1-6.
7. Product information. Ella (ulipristal acetate). Morristown, NJ: Watson
Pharma, Inc., August 2010.
8. American College of Obstetricians and Gynecologists. ACOG practice
bulletin no. 112: emergency contraception. Obstet Gynecol 2010;115:
1100-9. DOI 10.1097/AOG.0b013e3181deff2a
9. Chabert-Buffet N, Meduri G, Bouchard P, Spitz IM. Selective progesterone modulators and progesterone antagonists: mechanisms of action
and clinical applications. Hum Reprod Update 2005;11:293-307.
DOI 10.1093/humupd/dmi002
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effect on the endometrium. Curr Opin Obstet Gynecol 2009;21:318-24.
DOI 10.1097/GCO.0b013e32832e07e8

theannals.com

Acetato de Ulipristal para Anticoncepcin de Emergencia

SE Snow, SN Melillo, y CI Jarvis
Ann Pharmacother 2011;45:780-6.
EXTRACTO

Revisar la farmacologa, farmacocintica, eficacia y seguridad

de los datos sobre acetato de ulipristal, un nuevo anticonceptivo de
emergencia aprobado para uso hasta en 120 horas.
FUENTES DE DATOS: Artculos pertinentes al tpico fueron identificados y
revisados mediante bsquedas en PubMed (mayo 1994marzo 2011) y
clinicaltrials.gov usando los trminos claves ulipristal y CDB-2914. Se
obtuvieron y revisaron documentos de aprobacin Ella de Drugs@FDA
en la pgina en Internet de la Administracin de Alimentos y Drogas
(FDA).
SELECCIN DE ESTUDIOS Y EXTRACCIN DE DATOS: Todos los datos
publicados y documentos de aprobacin de FDA que examinan estudios
farmacolgicos, farmacocinticos y clnicos relacionados con acetato de
ulipristal como un anticonceptivo de emergencia fueron evaluados. Los
estudios seleccionados incluyeron tres (3) ensayos aleatorios y un (1)
meta-anlisis de acetato de ulipristal.
SNTESIS DE DATOS: Acetato de ulipristal es un anticonceptivo de
emergencia agonista/antagonista de progesterona aprobado para la
prevencin de embarazo para ser tomado lo antes posible dentro de 120
horas luego de relaciones sexuales no protegidas o falla conocida o
sospechada del anticonceptivo. Segn resultados de ensayos clnicos
fase 3 usados para obtener aprobacin, la administracin de acetato de
ulipristal fue por lo menos tan efectiva como la de levonorgestrel en la
reduccin de la tasa de embarazo cuando se estudia sola luego de
relaciones sexuales no protegidas y cuando se toma hasta dentro de 120
horas luego de relaciones sexuales no protegidas. Los efectos adversos
asociados con acetato de ulipristal reportados comnmente en los
ensayos incluyeron dolor de cabeza, sensibilidad de los senos, nusea y
dolor abdominal.
CONCLUSIONES: El acetato de ulipristal es efectivo como anticonceptivo
de emergencia por hasta 120 horas luego de relaciones sexuales no
protegidas. Como ulipristal est disponible solamente mediante receta,
puede ser cubierto por el seguro de la mujer. No obstante, los factores
adicionales de gastos de viaje y tiempo para hacer y asistir a citas
mdicas deben tomarse en cuenta al considerar el uso de ulipristal como
un anticonceptivo de emergencia. Debido a la similaridad de su
OBJETIVO:

The Annals of Pharmacotherapy

2011 June, Volume 45

785

SE Snow et al.

estructura con mifepristona, se ha levantado controversia en relacin al

mecanismo de accin de ulipristal.
Traducido por Ana E Vlez

LActate dUlipristal pour la Contraception dUrgence

SE Snow, SN Melillo, et CI Jarvis
Ann Pharmacother 2011;45:780-6.
RSUM
OBJECTIF: Revoir la pharmacologie, la pharmacocintique, lefficacit, et
linnocuit de lactate dulipristal (Ella, Watson Pharmaceutical) un
nouveau contraceptive durgence approuv pour utilisation jusqu 120
heures aprs le rapport sexuel.
PROVENANCE DES DONNES: Les publications concernant le sujet ont t
identifies partir dune revue de la banque de donnes PubMed (mai
1994-mars 2011) et le site clinicaltrials.gov en utilisant les mots cls
ulipristal et CDB-2914. Le rsum des informations sous-tendant
lapprobation du produit Ella aux tats-Unis a t obtenu partir du site
internet de la FDA des tats-Unis et a t revu.

786

The Annals of Pharmacotherapy

Toutes les donnes publies portant sur la

pharmacologie, la pharmacocintique et les tudes cliniques de lactate
dulipristal en contraception durgence, de mme que le rsum de la
FDA ont t valus. Trois tudes rpartition alatoire et une mtaanalyse ont t slectionnes.
RSUM: Lactate dulipristal est un agoniste/antagoniste de la
progestrone approuv pour prvenir une grossesse en situation
durgence. Il doit tre administr ds que possible et jusqu 120 heures
aprs un rapport sexuel non protg ou un chec connu ou suspect de
contraception. Daprs les rsultats dune tude pivot de phase 3,
ladministration dactate dulipristal est au moins aussi efficace que le
levonorgestrel pour prvenir la grossesse en situation durgence. Les
effets secondaires les plus frquemment rapports incluaient maux de
tte, sensibilit aux seins, nauses, et douleurs abdominales.
CONCLUSIONS: Lactate dulipristal est efficace en contraception
durgence jusqu 120 heures aprs un rapport sexuel non protg.
Lutilisation de lulipristal requiert une prescription du mdecin. Le
temps, les cots et le dlai associs la ncessit de voir un mdecin
doivent tre pris en considration lors de son utilisation comme
contraceptif durgence. De plus, comme sa structure chimique est
similaire celle de la mifepristone, une certaine controverse existe.
SLECTION DES DONNES:

2011 June, Volume 45

Traduit par Suzanne Laplante

theannals.com