4.1. Therapeutic indications

Emergency contraception within 120 hours (5 days) of unprotected sexual intercourse or contraceptive failure.

4.2. Posology and method of administration

Posology

The treatment consists of one tablet to be taken orally as soon as possible, but no later than 120 hours (5 days) after unprotected intercourse or contraceptive failure.

This tablet can be taken at any time during the menstrual cycle.

If vomiting occurs within 3 hours of the tablet intake, another tablet should be taken.

If a woman's menstrual period is late or in case of symptoms of pregnancy, pregnancy should be excluded before the tablet is administered.

Special populations

Renal impairment

No dose adjustment is necessary.

Hepatic impairment

In the absence of specific studies, no alternate dose recommendations for Ulipristal 30 mg film-coated tablet can be made.

Severe hepatic impairment

In the absence of specific studies, Ulipristal 30 mg film-coated tablet is not recommended.

Paediatric population

There is no relevant use of ulipristal acetate for children of prepubertal age in the indication emergency contraception.

Adolescents: ulipristal acetate is suitable for any woman of child bearing age, including adolescents. No differences in safety or efficacy have been shown compared to adult women aged 18 and older (see section 5.1).

Method of administration

Oral use.

The tablet can be taken with or without food.

4.3. Contraindications

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

4.4. Special warnings and precautions for use

Ulipristal acetate 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).

Ulipristal acetate does not prevent pregnancy in every case.

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 ulipristal acetate 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).

Contraception after ulipristal acetate intake

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 does not contraindicate the continued use of regular hormonal contraception, ulipristal acetate 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 ulipristal acetate, however, she should be advised to use a reliable barrier method until the next menstrual period.

Specific populations

Concomitant use of ulipristal acetate 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.

Excipients

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product..

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.

4.5. Interaction with other medicinal products and other forms of interaction

Potential for other medicinal products to affect ulipristal acetate

Ulipristal acetate is metabolized by CYP3A4 in vitro.

- CYP3A4 inducers

In vivo results show that the administration of ulipristal acetate with a strong CYP3A4 inducer such as rifampicin markedly decreases Cmax and AUC of ulipristal acetate by 90% or more and decreases ulipristal acetate half-life by 2.2-fold corresponding to an approximately 10-fold decrease of ulipristal acetate exposure. Concomitant use of Ulipristal 30 mg film-coated tablet with CYP3A4 inducers (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 and nevirapine) therefore reduces plasma concentrations of ulipristal acetate and may result in a decreased efficacy of Ulipristal 30 mg film-coated tablet.

For women who have used enzyme-inducing drugs in the past 4 weeks, Ulipristal 30 mg film-coated tablet is not recommended (see section 4.4) and non-hormonal emergency contraception (i.e. a copper intrauterine device (Cu-IUD)) should be considered.

- CYP3A4 inhibitors

In vivo results show that administration of ulipristal acetate with a potent and a moderate CYP3A4 inhibitor increased Cmax and AUC of ulipristal acetate with a maximum of 2- and 5.9-fold, respectively. The effects of CYP3A4 inhibitors are unlikely to have any clinical consequences.

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.

Medicinal products affecting gastric pH

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.

Potential for ulipristal acetate to affect other medicinal products

Hormonal contraceptives

Because ulipristal acetate binds to the progesterone receptor with high affinity, it may interfere with the action of progestogen-containing medicinal products:

- Contraceptive action of combined hormonal contraceptives and progestogen-only contraception may be reduced

- Concomitant use of ulipristal acetate and emergency contraception containing levonorgestrel is not recommended (see section 4.4).

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.

P-glycoprotein (P-gp) substrates

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.

4.6. Fertility, pregnancy and lactation

Pregnancy

Ulipristal 30 mg film-coated tablet 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 30 mg film-coated tablet 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 ulipristal acetate do not suggest any safety concern. Nevertheless, it is important that any pregnancy in a woman who has taken Ulipristal 30 mg film-coated tablet be reported to www.ulipristal-pregnancy-registry.com. The purpose of this web-based registry is to collect safety information from women who have taken Ulipristal 30 mg film-coated tablet during pregnancy or who become pregnant after Ulipristal 30 mg film-coated tablet intake. All patient data collected will remain anonymous.

Breast-feeding

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 30 mg film-coated tablet, breastfeeding is not recommended for one week. During this time it is recommended to express and discard the breast milk in order to stimulate lactation.

Fertility

A rapid return of fertility is likely following treatment with Ulipristal 30 mg film-coated tablet for emergency contraception.

Women should be advised to use a reliable barrier method for all subsequent acts of intercourse until the next menstrual period.

4.7. Effects on ability to drive and use machines

Ulipristal acetate may have minor or moderate influence on the ability to drive or use machines: mild to moderate dizziness is common after Ulipristal 30 mg film-coated tablet 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).

4.8. Undesirable effects

Summary of the safety profile

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.

Tabulated list of adverse reactions

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).

MedDRA

Adverse reactions (frequency)

System Organ Class

Common

Uncommon

Rare

Infections and infestations

Influenza

Immune system disorders

Hypersensitivity reactions including rash, urticaria, angioedema

Metabolism and nutrition disorders

Appetite disorders

Psychiatric disorders

Mood disorders

Emotional disorder

Anxiety

Insomnia

Hyperactivity disorder

Libido changes

Disorientation

Nervous system disorders

Headache

Dizziness

Somnolence

Migraine

Tremor

Disturbance in attention

Dysgueusia

Syncope

Eye disorders

Visual disturbance

Abnormal sensation in eye

Ocular hyperaemia

Photophobia

Ear and labyrinth disorders

Vertigo

Respiratory, thoracic and mediastinal disorders

Dry throat

Gastrointestinal disorders

Nausea*

Abdominal pain*

Abdominal discomfort

Vomiting*

Diarrhoea

Dry mouth

Dyspepsia

Flatulence

Skin and subcutaneous tissue disorders

Acne

Skin lesion

Pruritus

Musculoskeletal and connective tissue disorders

Myalgia

Back pain

Reproductive system and breast disorders

Dysmenorrhea

Pelvic pain

Breast tenderness

Menorrhagia

Vaginal discharge

Menstrual disorder

Metrorrhagia

Vaginitis

Hot flush

Premenstrual syndrome

Genital pruritus

Dyspareunia

Ruptured ovarian cyst

Vulvovaginal pain

Hypomenorrhea*

General disorders and administration site conditions

Fatigue

Chills

Malaise

Pyrexia

Thirst

*Symptom which could also be related to an undiagnosed pregnancy (or related complications)

Adolescents: 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 (Section 4.2).

Post-marketing experience: 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.

Description of selected adverse reactions

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 ulipristal acetate 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 ulipristal acetate (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 events, change in duration or volume of menses or incidence of intermenstrual bleeding.

Reporting of suspected adverse reactions

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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Experience with ulipristal acetate overdose is limited. Single doses up to 200 mg have been used in women without safety concern. Such high doses were well-tolerated; however, these women had a shortened menstrual cycle (uterine bleeding occurring 2-3 days earlier than would be expected) and in some women, the duration of bleeding was prolonged, although not excessive in amount (spotting).

There are no antidotes and further treatment should be symptomatic.