EllaOne 30 mg 1 film-coated tablet oral

In compliance with article 118 "authorization of advertising to the public" of the legislative decree of 24 April 2006, number 219

INDICATIONS

Emergency contraceptive to be taken within 120 hours (5 days) of unprotected sexual intercourse or failure of another contraceptive method.

CONTRAINDICATIONS

Hypersensitivity to the active substance or to any of the excipients listed in paragraph 6.1.

WARNINGS AND PRECAUTIONS FOR USE

ellaOne is intended for occasional use only. ellaOne should never replace the use of a regular contraceptive method. In any case, women should be advised to use a regular method of contraception. Ulipristal acetate is not intended for use during pregnancy and should not be taken by women who are actually or suspected of being pregnant. In any case, ellaOne does not terminate an existing pregnancy (see section 4.6). ellaOne does not prevent pregnancy in all cases In case of a delay of more than 7 days in the onset of the next menstruation, if the bleeding of the expected menstruation is abnormal or if there are symptoms indicating pregnancy or in case of doubt, a pregnancy test should be performed. As with any pregnancy, the possibility of an ectopic pregnancy must be considered. It is important to know that the presence of uterine bleeding does not exclude the possibility of an ectopic pregnancy. Women who become pregnant after taking ulipristal acetate should contact their doctor (see section 4.6). Ulipristal acetate inhibits or delays ovulation (see section 5.1). If ovulation has already occurred, it is no longer effective. Since it is not possible to predict the time of ovulation, the tablet should be taken as soon as possible after unprotected sexual intercourse. There is no data available on the effectiveness of ulipristal acetate taken more than 120 hours (5 days) after unprotected intercourse. Limited and inconclusive data suggest that ellaOne may be less effective 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 body weight or BMI. After taking the tablet, your period may come a few days earlier or later than expected. In approximately 7% of women, menstruation occurred more than 7 days earlier than expected. In 18.5% of women there was a delay of more than 7 days, while in 4% of patients the delay exceeded 20 days. Taking ulipristal acetate concomitantly with an emergency contraceptive containing levonorgestrel is not recommended (see section 4.5). Contraception after taking ellaOne Ulipristal acetate is an emergency contraceptive that reduces the risk of pregnancy after unprotected intercourse, but does not confer contraceptive protection in subsequent intercourse, therefore after the use of emergency contraception women should be advised to use a reliable barrier method until the next menstruation. Although continuous use of a regular hormonal contraceptive is not contraindicated when taking ulipristal acetate for emergency contraception, ellaOne may reduce its contraceptive efficacy (see section 4.5). Consequently, if a patient wishes to start or continue using a hormonal contraceptive, she may do so after taking ellaOne, however women should be advised to use a reliable barrier method of contraception until the next menstrual period occurs. Special populations Concomitant use of ellaOne with CYP3A4 inducing drugs is not recommended due to their interaction (e.g. barbiturates (including primidone and phenobarbital), phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, herbal medicines containing Hypericum perforatum (St. John's Wort), rifampicin, rifabutin, griseofulvin, efavirenz, nevirapine and long-term use of ritonavir). The use of ellaOne in women with severe asthma receiving oral glucocorticoids is not recommended. This medicine contains lactose. Patients suffering from rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine. This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.

INTERACTIONS

Potential for other drugs to interfere with ulipristal acetate Ulipristal acetate is metabolised by CYP3A4 in vitro. - CYP3A4 inducers The results alive show that administration of ulipristal acetate with a strong CYP3A4 inducer such as rifampin markedly reduces C_max and AUC of ulipristal acetate by at least 90% and decreases the half-life of ulipristal acetate by 2.2-fold, with a corresponding reduction in exposure to ulipristal acetate by approximately 10-fold. For this reason, the concomitant use of ellaOne with CYP3A4 inducers (e.g. barbiturates (including primidone and phenobarbital), phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, herbal medicines containing Hypericum perforatum (St. John's Wort), rifampicin, rifabutin, griseofulvin, efavirenz and nevirapine) reduces plasma concentrations of ulipristal acetate, with a consequent possible reduction in the efficacy of ellaOne. For women who have used enzyme-inducing medicinal products in the last 4 weeks, ellaOne is not recommended (see section 4.4) and the use of non-hormonal emergency contraception (i.e. copper intrauterine coil, Cu-IUD) should be considered. - CYP3A4 inhibitors Results alive demonstrated that concomitant administration of ulipristal acetate with a strong inhibitor and a moderate inhibitor of CYP3A4 increases C_max and AUC of ulipristal acetate up to a maximum of 2 and 5.9 times, respectively. The effects of CYP3A4 inhibitors are unlikely to have clinical consequences. The CYP3A4 inhibitor ritonavir may also have an inducing effect on CYP3A4 if it is used for a prolonged period. In such cases, ritonavir may reduce plasma concentrations of ulipristal acetate. Concomitant use of these medicinal products is therefore not recommended (see section 4.4). The enzyme induction wears off slowly and the effects on the plasma concentration of ulipristal acetate may occur even if the woman has stopped taking an enzyme inducer within the last 4 weeks. Medicines that affect gastric pH Concomitant administration of ulipristal acetate (10 mg tablet) with the proton pump inhibitor esomeprazole (20 mg daily for 6 days) resulted in a mean reduction in C_max of approximately 65%, a delay of the T_max (from a median of 0.75 hours to 1.0 hours) and an increase in the average area under the curve (AUC) of 13%. The clinical relevance of this interaction for the administration of a single dose of ulipristal acetate as emergency contraception is unknown. Potential ability for ulipristal acetate to interfere with other medicines Hormonal contraceptives Because ulipristal acetate binds with great affinity to the progesterone receptor, it may interfere with the action of progestin-containing medicines. - The contraceptive action of combined hormonal contraceptives and progestin-only contraceptives may be reduced. - Concomitant use of ulipristal acetate and an emergency contraceptive method containing levonorgestrel is not recommended (see section 4.4). The data in vitro 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 administration of a single dose, induction of CYP1A2 and CYP3A4 by ulipristal acetate or its active metabolite is unlikely to occur. It is therefore unlikely that the administration of ulipristal acetate alters the clearance of medicinal products metabolised by these enzymes. P-glycoprotein (P-gp) substrates The data in vitro indicate that ulipristal acetate may be an inhibitor of P-gp at clinically relevant concentrations. The results alive with the P-gp substrate fexofenadine did not provide definitive results. The effects of P-gp substrates are unlikely to have clinical consequences.

SIDE EFFECTS

Safety profile summary The most frequently reported adverse reactions were headache, nausea, abdominal pain and dysmenorrhea. The safety of ulipristal acetate was evaluated in 4,718 women during the clinical development program. Table of adverse reactions The following table reports the adverse reactions recorded in the phase III program on 2,637 women. The adverse reactions listed below are ranked by 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 (frequency cannot be estimated from the available data).

MedDRA | Adverse reactions (frequency)

Classification by systems and organs | Municipality | Uncommon | Rare

Infections and infestations | Uncommon : Influence

Immune system disorders | Rare : hypersensitivity reactions including rash, urticaria, angioedema**

Metabolism and nutrition disorders | Uncommon : Appetite disorders

Psychiatric disorders | Municipality : Mood disorders | Uncommon : Emotional disorders, Anxiety, Insomnia, Hyperactivity disorders, Libido changes | Rare : Disorientation

Nervous system disorders | Municipality : Headache, Dizziness | Uncommon : Drowsiness, Migraine | Rare : Tremors, Attention disorders, Dysgeusia, Syncope

Eye diseases | Uncommon : Visual disturbances | Rare : Abnormal ocular sensation, Ocular hyperemia, Photophobia

Ear and labyrinth disorders | Rare : Dizziness

Respiratory, thoracic and mediastinal disorders | Rare : Dry throat

Gastrointestinal disorders | Municipality : Nausea*, Abdominal pain*, Discomfort, abdominal, Vomiting* | Uncommon : Diarrhoea, Dry mouth, Dyspepsia, Flatulence

Skin and subcutaneous tissue disorders | Uncommon : Acne, Skin lesions, Itching

Musculoskeletal system and connective tissue disorders | Municipality : Myalgia, Back pain

Reproductive system and breast disorders | Municipality : Dysmenorrhea, Pelvic pain, Breast tenderness | Uncommon : Menorrhagia, Vaginal discharge, Menstrual disorders, Metrorrhagia, Vaginitis, Hot flashes, Premenstrual syndrome | Rare : Genital itching, Dyspareunia, Ruptured ovarian cyst, Vulvo-vaginal pain, Hypomenorrhea*

Systemic disorders and conditions relating to the administration site | Municipality : Fatigue | Uncommon : Chills, Malaise, Pyrexia | Rare : Thirst

*Symptom that may also be related to an undiagnosed pregnancy (or related complications) **Adverse reaction from spontaneous reports Adolescents: the safety profile observed in women under 18 years of age in studies and post-marketing experience is similar to that observed in adult women during the phase III program (see section 4.2). Post-marketing: Adverse reactions reported spontaneously in the post-marketing phase were similar in nature and frequency to the safety profile described during the phase III program. Description of some adverse reactions The majority of women (74.6%) in phase III studies had their periods after the expected date or within ± 7 days, while in 6.8% of them the period appeared more than 7 days earlier than expected and 18.5% had a delay of more than 7 days from the expected date of onset of menstruation. The delay was greater than 20 days in 4% of women. A minority (8.7%) of women reported intermenstrual bleeding for an average duration of 2.4 days. In the majority of cases (88.2%) the bleeding was described as spotting. Among women who took ellaOne in phase III trials, only 0.4% reported heavy intermenstrual bleeding. In the phase III studies, 82 women were enrolled more than once and therefore received more than one dose of ellaOne (73 women were enrolled twice and 9 women were enrolled three times). No differences in the safety of these subjects were observed in terms of incidence and severity of adverse reactions, changes in duration or volume of menses, or incidence of intermenstrual bleeding. Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: Italian Medicines Agency. Website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.