Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: LABORATOIRE HRA PHARMA, 200 avenue de Paris, 92320, CHATILLON, France
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
ellaOne is for occasional use only. It should in no instance replace a regular contraceptive method. In any case, women should be advised to adopt a regular method of contraception.
Ulipristal acetate is not intended for use during pregnancy and should not be taken by any woman suspected or known to be pregnant. However, it does not interrupt an existing pregnancy (see section 4.6).
In case the next menstrual period is more than 7 days late, if the menstrual period is abnormal in character or if there are symptoms suggestive of pregnancy or in case of doubt, a pregnancy test should be performed. As with any pregnancy, the possibility of an ectopic pregnancy should be considered. It is important to know that the occurrence of uterine bleeding does not rule out ectopic pregnancy. Women who become pregnant after taking ulipristal acetate should contact their doctor (see section 4.6).
ulipristal acetate inhibits or postpones ovulation (see section 5.1). If ovulation has already occurred, it is no longer effective. The timing of ovulation cannot be predicted and therefore the tablet should be taken as soon as possible after unprotected intercourse.
No data are available on the efficacy of ulipristal acetate when taken more than 120 hours (5 days) after unprotected intercourse.
Limited and inconclusive data suggest that there may be reduced efficacy of ellaOne with increasing body weight or body mass index (BMI) (see section 5.1). In all women, emergency contraception should be taken as soon as possible after unprotected intercourse, regardless of the woman’s body weight or BMI.
After the tablet intake menstrual periods can sometimes occur a few days earlier or later than expected. In approximately 7% of the women, menstrual periods occurred more than 7 days earlier than expected. In 18.5% of the women a delay of more than 7 days occurred, and in 4% the delay was greater than 20 days.
Concomitant use of ulipristal acetate and emergency contraception containing levonorgestrel is not recommended (see section 4.5).
Ulipristal acetate is an emergency contraceptive that decreases pregnancy risk after unprotected intercourse but does not confer contraceptive protection for subsequent acts of intercourse. Therefore, after using emergency contraception, women should be advised to use a reliable barrier method until her next menstrual period.
Although the use of ulipristal acetate for emergency contraception does not contraindicate the continued use of regular hormonal contraception, ellaOne may reduce its contraceptive action (see section 4.5). Therefore, if a woman wishes to start or continue using hormonal contraception, she can do so after using ellaOne, however, she should be advised to use a reliable barrier method until the next menstrual period.
Concomitant use of ellaOne with CYP3A4 inducers is not recommended due to interaction (e.g. barbiturates (including primidone and phenobarbital), phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, herbal medicinal products containing Hypericum perforatum (St. John’s wort), rifampicin, rifabutin, griseofulvin, efavirenz, nevirapine and long term use of ritonavir).
Use in women with severe asthma treated by oral glucocorticoid is not recommended.
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Ulipristal acetate is metabolised by CYP3A4 in vitro.
The CYP3A4 inhibitor ritonavir can also have an inducing effect on CYP3A4 when ritonavir is used for a longer period. In such cases ritonavir might reduce plasma concentrations of ulipristal acetate. Concomitant use is therefore not recommended (see section 4.4). Enzyme induction wears off slowly and effects on the plasma concentrations of ulipristal acetate may occur even if a woman has stopped taking an enzyme inducer in the past 4 weeks.
Administration of ulipristal acetate (10 mg tablet) together with the proton pump inhibitor esomeprazole (20 mg daily for 6 days) resulted in approximately 65% lower mean Cmax, a delayed Tmax (from a median of 0.75 hours to 1.0 hours) and 13% higher mean AUC. The clinical relevance of this interaction for single dose administration of ulipristal acetate as emergency contraception is not known.
Because ulipristal acetate binds to the progesterone receptor with high affinity, it may interfere with the action of progestogen-containing medicinal products:
In vitro data indicate that ulipristal acetate and its active metabolite do not significantly inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4, at clinically relevant concentrations. After single dose administration induction of CYP1A2 and CYP3A4 by ulipristal acetate or its active metabolite is not likely. Thus, administration of ulipristal acetate is unlikely to alter the clearance of medicinal products that are metabolised by these enzymes.
In vitro data indicate that ulipristal acetate may be an inhibitor of P-gp at clinically relevant concentrations. Results in vivo with the P-gp substrate fexofenadine were inconclusive. The effects of the P-gp substrates are unlikely to have any clinical consequences.
ellaOne is not intended for use during pregnancy and should not be taken by any woman suspected or known to be pregnant (see section 4.2).
Ulipristal acetate does not interrupt an existing pregnancy.
Pregnancy may occasionally occur after ulipristal acetate intake. Although no teratogenic potential has been observed, animal data are insufficient with regard to reproduction toxicity (see section 5.3). Limited human data regarding pregnancy exposure to ellaOne do not suggest any safety concern. Nevertheless it is important that any pregnancy in a woman who has taken ellaOne be reported to www.hra-pregnancy-registry.com. The purpose of this web-based registry is to collect safety information from women who have taken ellaOne during pregnancy or who become pregnant after ellaOne intake. All patient data collected will remain anonymous.
Ulipristal acetate is excreted in breast milk (see section 5.2). The effect on newborn/infants has not been studied. A risk to the breastfed child cannot be excluded. After intake of ulipristal acetate for emergency contraception, breast-feeding is not recommended for one week. During this time it is recommended to express and discard the breast milk in order to stimulate lactation.
A rapid return of fertility is likely following treatment with ulipristal acetate for emergency contraception. Women should be advised to use a reliable barrier method for all subsequent acts of intercourse until the next menstrual period.
Ulipristal acetate has minor or moderate influence on the ability to drive or use machines: mild to moderate dizziness is common after ellaOne intake, somnolence and blurred vision are uncommon; disturbance in attention has been rarely reported. The patient should be informed not to drive or use machines if they are experiencing such symptoms (see section 4.8).
The most commonly reported adverse reactions were headache, nausea, abdominal pain and dysmenorrhea.
Safety of ulipristal acetate has been evaluated in 4,718 women during the clinical development program.
The adverse reactions reported in the phase III program of 2,637 women are provided in the table below.
Adverse reactions listed below are classified according to frequency and system organ class using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).
Uncommon: Influenza
Uncommon: Appetite disorders
Common: Mood disorders
Uncommon: Emotional disorder, Anxiety, Insomnia, Hyperactivity disorder, Libido changes
Rare: Disorientation
Common: Headache, Dizziness
Uncommon: Somnolence, Migraine
Rare: Tremor, Disturbance in attention, Dysgueusia, Syncope
Uncommon: Visual disturbance
Rare: Abnormal sensation in eye, Ocular hyperaemia, Photophobia
Rare: Vertigo
Rare: Dry throat
Common: Nausea*, Abdominal pain*, Abdominal discomfort, Vomiting*
Uncommon: Diarrhoea, Dry mouth, Dyspepsia, Flatulence
Uncommon: Acne, Skin lesion, Pruritus
Rare: Urticaria
Common: Myalgia, Back pain
Common: Dysmenorrhea, Pelvic pain, Breast tenderness
Uncommon: Menorrhagia, Vaginal discharge, Menstrual disorder, Metrorrhagia, Vaginitis, Hot flush, Premenstrual syndrome
Rare: Genital pruritus, Dyspareunia, Ruptured ovarian cyst, Vulvovaginal pain, Hypomenorrhea*
Common: Fatigue
Uncommon: Chills, Malaise, Pyrexia
Rare: Thirst
* Symptom which could also be related to an undiagnosed pregnancy (or related complications)
The safety profile observed in women less than 18 years old in studies and post-marketing is similar to the safety profile in adults during the phase III program (see section 4.2).
The adverse reactions spontaneously reported in post-marketing experience were similar in nature and frequency to the safety profile described during the phase III program.
The majority of women (74.6%) in the phase III studies had their next menstrual period at the expected time or within ± 7 days, while 6.8% experienced menses more than 7 days earlier than expected and 18.5% had a delay of more than 7 days beyond the anticipated onset of menses. The delay was greater than 20 days in 4% of the women.
A minority (8.7%) of women reported intermenstrual bleeding lasting an average of 2.4 days. In a majority of cases (88.2%), this bleeding was reported as spotting. Among the women who received ellaOne in the phase III studies, only 0.4% reported heavy intermenstrual bleeding.
In the phase III studies, 82 women entered a study more than once and therefore received more than one dose of ellaOne (73 women enrolled twice and 9 enrolled three times). There were no safety differences in these subjects in terms of incidence and severity of adverse reactions, change in duration or volume of menses or incidence of intermenstrual bleeding.
Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
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