Esmya

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

2 

1. NAME OF THE MEDICINAL PRODUCT 

 

Esmya 5 mg tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each tablet contains 5 mg of ulipristal acetate. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Tablet. 

White to off-white, round biconvex tablet of 7 mm engraved with “ES5” on one face. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Ulipristal acetate is indicated for one treatment course of pre-operative treatment of moderate to 

severe symptoms of uterine fibroids in adult women of reproductive age. 

 

Ulipristal acetate is indicated for intermittent treatment of moderate to severe symptoms of uterine 

fibroids in adult women of reproductive age who are not eligible for surgery. 

 

4.2 Posology and method of administration 
 

Esmya treatment is to be initiated and supervised by physicians experienced in the diagnosis and 

treatment of uterine fibroids. 

 

Posology 

The treatment consists of one tablet of 5 mg to be taken once daily for treatment courses of up to 

3 months each. Tablets may be taken with or without food. 

Treatments should only be initiated when menstruation has occurred: 

- The first treatment course should start during the first week of menstruation. 

- Re-treatment courses should start at the earliest during the first week of the second menstruation 

following the previous treatment course completion. 

The treating physician should explain to the patient the requirement for treatment free intervals. 

Repeated intermittent treatment has been studied up to 4 intermittent courses. 

 

If a patient misses a dose, the patient should take ulipristal acetate as soon as possible. If the dose was 

missed by more than 12 hours, the patient should not take the missed dose and simply resume the 

usual dosing schedule. 

 

Special population 

Renal impairment 

No dose adjustment is recommended in patients with mild or moderate renal impairment. In the 

absence of specific studies, ulipristal acetate is not recommended in patients with severe renal 

impairment unless the patient is closely monitored (see sections 4.4 and 5.2). 

 

Paediatric population 

There is no relevant use of ulipristal acetate in the paediatric population. The safety and efficacy of 

ulipristal acetate was only established in women of 18 years and older. 



 

3 

 

Method of administration 

Oral use. Tablets should be swallowed with water. 

 

4.3 Contraindications 

 

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

Pregnancy and breastfeeding. 

Genital bleeding of unknown aetiology or for reasons other than uterine fibroids. 

Uterine, cervical, ovarian or breast cancer. 

Underlying hepatic disorder. 

 

4.4 Special warnings and precautions for use 

 

Ulipristal acetate should only be prescribed after careful diagnosis. Pregnancy should be precluded 

prior to treatment. If pregnancy is suspected prior to initiation of a new treatment course, a pregnancy 

test should be performed. 

 

Contraception 

Concomitant use of progestagen-only pills, a progestagen-releasing intrauterine device or combined 

oral contraceptive pills is not recommended (see section 4.5). Although a majority of women taking a 

therapeutic dose of ulipristal acetate have anovulation, a non hormonal contraceptive method is 

recommended during treatment. 

 

Endometrial changes 

Ulipristal acetate has a specific pharmacodynamic action on the endometrium: 

Changes in the histology of the endometrium may be observed in patients treated with ulipristal 

acetate. These changes are reversible after treatment cessation. 

These histological changes are denoted as “Progesterone Receptor Modulator Associated Endometrial 

Changes” (PAEC) and should not be mistaken for endometrial hyperplasia (see sections 4.8 and 5.1). 

In addition, reversible increase of the endometrium thickness may occur under treatment. 

 

In case of repeated intermittent treatment, periodic monitoring of the endometrium is recommended. 

This includes annual ultrasound to be performed after resumption of menstruation during 

off-treatment period. 

 

If endometrial thickening is noted, which persists after return of menstruations during off-treatment 

periods or beyond 3 months following the end of treatment courses, and/or an altered bleeding pattern 

is noted (see section "Bleeding pattern" below), investigation including endometrial biopsy should be 

performed in order to exclude other underlying conditions, including endometrial malignancy. 

 

In case of hyperplasia (without atypia), monitoring as per usual clinical practice (e.g. a follow-up 

control 3 months later) would be recommended. In case of atypical hyperplasia, investigation and 

management as per usual clinical practice should be performed. 

 

The treatment courses should each not exceed 3 months as the risk of adverse impact on the 

endometrium is unknown if treatment is continued without interruption. 

 

Bleeding pattern 

Patients should be informed that treatment with ulipristal acetate usually leads to a significant 

reduction in menstrual blood loss or amenorrhea within the first 10 days of treatment. Should the 

excessive bleeding persist, patients should notify their physician. Menstrual periods generally return 

within 4 weeks after the end of each treatment course. 

If, during repeated intermittent treatment, after the initial reduction in bleeding or amenorrhea, an 

altered persistent or unexpected bleeding pattern occurs, such as inter-menstrual bleeding, 



 

4 

investigation of the endometrium including endometrial biopsy should be performed in order to 

exclude other underlying conditions, including endometrial malignancy. 

 

Repeated intermittent treatment has been studied up to 4 intermittent treatment courses. 

 

Renal impairment 

Renal impairment is not expected to significantly alter the elimination of ulipristal acetate. In the 

absence of specific studies, ulipristal acetate is not recommended for patients with severe renal 

impairment unless the patient is closely monitored (see section 4.2). 

 

Hepatic injury 

During the post-marketing experience, cases of liver injury and hepatic failure were reported (see 

section 4.3). 

Liver function tests must be performed before starting treatment. Treatment must not be initiated if 

transaminases (alanine transaminase (ALT) or aspartate aminotransferase (AST)) exceed 2 x ULN 

(isolated or in combination with bilirubin >2 x ULN). 

During treatment, liver function tests must be performed monthly during the first 2 treatment courses. 

For further treatment courses, liver function must be tested once before each new treatment course 

and when clinically indicated. 

If a patient during treatment shows signs or symptoms compatible with liver injury (fatigue, asthenia, 

nausea, vomiting, right hypochondrial pain, anorexia, jaundice), treatment should be stopped and the 

patient should be investigated immediately, and liver function tests performed. 

Patients who develop transaminase levels (ALT or AST) > 3 times the upper limit of normal during 

treatment should stop treatment and be closely monitored. 

In addition liver testing should be performed 2- 4 weeks after treatment has stopped. 

 

Concomitant treatments 

Co-administration of moderate (e.g. erythromycin, grapefruit juice, verapamil) or potent (e.g. 

ketoconazole, ritonavir, nefazodone, itraconazole, telithromycin, clarithromycin) CYP3A4 inhibitors 

and ulipristal acetate is not recommended (see section 4.5). 

 

Concomitant use of ulipristal acetate and potent CYP3A4 inducers (e.g. rifampicin, rifabutin, 

carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, primidone, St John´s wort, 

efavirenz, nevirapine, long term use of ritonavir) is not recommended (see section 4.5). 

 

Asthma patients 

Use in women with severe asthma insufficiently controlled by oral glucocorticoids is not 

recommended. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Potential for other medicinal products to affect ulipristal acetate: 

 

Hormonal contraceptives 

Ulipristal acetate has a steroid structure and acts as a selective progesterone receptor modulator with 

predominantly inhibitory effects on the progesterone receptor. Thus hormonal contraceptives and 

progestagens are likely to reduce ulipristal acetate efficacy by competitive action on the progesterone 

receptor. Therefore concomitant administration of medicinal products containing progestagen is not 

recommended (see section 4.4 and 4.6). 

 

CYP3A4 inhibitors 

Following administration of the moderate CYP3A4 inhibitor erythromycin propionate (500 mg twice 

daily for 9 days) to healthy female volunteers, Cmax and AUC of ulipristal acetate increased 1.2 and 

2.9 fold, respectively; the AUC of the active metabolite of ulipristal acetate increased 1.5 fold while 

the Cmax of the active metabolite decreased (0.52 fold change). 

 



 

5 

Following administration of the potent CYP3A4 inhibitor ketoconazole (400 mg once daily for 

7 days) to healthy female volunteers, Cmax and AUC of ulipristal acetate increased 2 and 5.9 fold, 

respectively; the AUC of the active metabolite of ulipristal acetate increased 2.4 fold while the Cmax of 

the active metabolite decreased (0.53 fold change). 

 

No dose adjustment is considered necessary for administration of ulipristal acetate to patients 

receiving concomitant mild CYP3A4 inhibitors. Co-administration of moderate or potent CYP3A4 

inhibitors and ulipristal acetate is not recommended (see section 4.4). 

 

CYP3A4 inducers 

Administration of the potent CYP3A4 inducer rifampicin (300 mg twice daily for 9 days) to healthy 
female volunteers markedly decreased Cmax and AUC of ulipristal acetate and its active metabolite by 

90% or more and decreased ulipristal acetate half-life by 2.2-fold corresponding to an approximately 

10-fold decrease of ulipristal acetate exposure. Concomitant use of ulipristal acetate and potent 

CYP3A4 inducers (e.g. rifampicin, rifabutin, carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, 

phenobarbital, primidone, St John´s wort, efavirenz, nevirapine, long term use of ritonavir) is not 

recommended (see section 4.4). 

 

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. This effect of medicinal 

products that increase gastric pH is not expected to be of clinical relevance for daily administration of 

ulipristal acetate tablets. 

 

Potential for ulipristal acetate to affect other medicinal products: 

 

Hormonal contraceptives 

Ulipristal acetate may interfere with the action of hormonal contraceptive medicinal products 

(progestagen only, progestagen releasing devices or combined oral contraceptive pills) and 

progestagen administered for other reasons. Therefore concomitant administration of medicinal 

products containing progestagen is not recommended (see sections 4.4 and 4.6). Medicinal products 

containing progestagen should not be taken within 12 days after cessation of ulipristal acetate 

treatment. 

 

P-gp substrates 

In vitro data indicate that ulipristal acetate may be an inhibitor of P-gp at clinically relevant 

concentrations in the gastrointestinal wall during absorption. 

Simultaneous administration of ulipristal acetate and a P-gp substrate has not been studied and an 

interaction cannot be excluded. In vivo results show that ulipristal acetate (administered as a single 

10 mg tablet) 1.5 hour before administration of the P-gP substrate fexofenadine (60 mg) has no 

clinically relevant effects on the pharmacokinetic of fexofenadine. It is therefore recommended that 

co-administration of ulipristal acetate and P-gp substrates (e.g. dabigatran etexilate, digoxin, 

fexofenadine) should be separated in time by at least 1.5 hours. 

 

4.6 Fertility, pregnancy and lactation 

 

Contraception in females 

Ulipristal acetate is likely to adversely interact with progestagen-only pills, progestagen-releasing 

devices or combined oral contraceptive pills, therefore, concomitant use is not recommended. 

Although a majority of women taking a therapeutic dose of ulipristal acetate have anovulation, a non 

hormonal contraceptive method is recommended during treatment (see sections 4.4 and 4.5). 

 

Pregnancy 

Ulipristal acetate is contraindicated during pregnancy (see section 4.3). 

There are no or limited amount of data from the use of ulipristal acetate in pregnant women. 



 

6 

Although no teratogenic potential was observed, animal data are insufficient with regard to 

reproduction toxicity (see section 5.3). 

 

Breastfeeding 

Available toxicological data in animals have shown excretion of ulipristal acetate in milk (for details 

see section 5.3). Ulipristal acetate is excreted in human milk. The effect on newborn/infants has not 

been studied. A risk to the newborns/infants cannot be excluded. Ulipristal acetate is contraindicated 

during breastfeeding (see sections 4.3 and 5.2). 

 

Fertility 
A majority of women taking a therapeutic dose of ulipristal acetate have anovulation, however, the 

level of fertility while taking multiple doses of ulipristal acetate has not been studied. 

 

4.7 Effects on ability to drive and use machines 

 

Ulipristal acetate may have minor influence on the ability to drive or use machines as mild dizziness 

has been observed after ulipristal acetate intake. 

 

4.8 Undesirable effects 
 

Summary of the safety profile 

The safety of ulipristal acetate has been evaluated in 1,053 women with uterine fibroids treated with 

5 mg or 10 mg ulipristal acetate during Phase III studies. The most common finding in clinical trials 

was amenorrhea (79.2%), which is considered as a desirable outcome for the patients (see 

section 4.4). 

The most frequent adverse reaction was hot flush. The vast majority of adverse reactions were mild 

and moderate (95.0%), did not lead to discontinuation of the medicinal product (98.0%) and resolved 

spontaneously. 

Among these 1,053 women, the safety of repeated intermittent treatment courses (each limited to 

3 months) has been evaluated in 551 women with uterine fibroids treated with 5 or 10 mg ulipristal 

acetate in two phase III studies (including 446 women exposed to four intermittent treatment courses 

of whom 53 were exposed to eight intermittent treatment courses) and demonstrated a similar safety 

profile to that observed for one treatment course. 

 

Tabulated list of adverse reactions 

Based on pooled data from four phase III studies in patients with uterine fibroids treated for 3 months, 

the following adverse reactions have been reported. Adverse reactions listed below are classified 

according to frequency and system organ class. Within each frequency grouping, adverse reactions are 

presented in order of decreasing seriousness. Frequencies are defined as 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 available data). 

 



 

7 

 

System Organ 

Class 

Adverse reactions during treatment course 1 

Very common 

 

Common 

 

Uncommon 

 

Rare 

 

Frequency 

Not known  

Immune system 

disorders 
  

Drug 

hypersensitivity* 
 

 

Psychiatric 

disorders 

  Anxiety  

Emotional disorder 

  

Nervous system 

disorders 

 Headache* Dizziness    

Ear and labyrinth 

disorders 

 Vertigo     

Respiratory, 

thoracic and 

mediastinal 

disorders 

   Epistaxis  

 

 

Gastrointestinal 

disorders  

 Abdominal pain  

Nausea  

Dry mouth  

Constipation  

Dyspepsia  

Flatulence  

 

Hepatobiliary 

disorders 

    Hepatic 

failure 

Skin and 

subcutaneous 

tissue disorders 

 Acne  

 

Alopecia** 

Dry skin 

Hyperhidrosis 

 Angioedema 

Musculoskeletal 

and connective 

tissue disorders 

 Musculoskeletal 

pain  

Back pain    

Renal and urinary 

disorders 

  Urinary 

incontinence  

  

Reproductive 

system and breast 

disorders  

Amenorrhea  

Endometrial 

thickening*  

 

Hot flush* 

Pelvic pain  

Ovarian cyst* 

Breast 

tenderness/pain 

Uterine 

haemorrhage* 

Metrorrhagia  

Genital discharge  

Breast discomfort  

Ovarian cyst 

ruptured* 

Breast swelling  

 

 

General disorders 

and administration 

site conditions  

 Fatigue  Oedema  

Asthenia  

  

Investigations  Weight increased  Blood cholesterol 

increased  

Blood triglycerides 

increased 

  

* see section "Description of selected adverse reactions" 

** The verbatim term “mild hair loss” was coded to the term “alopecia” 

 

When comparing repeated treatment courses, overall adverse reactions rate was less frequent in 

subsequent treatment courses than during the first one and each adverse reaction was less frequent or 

remained in the same frequency category (except for dyspepsia which was classified as uncommon in 

treatment course 3 based on one patient occurence). 

 

Description of selected adverse reactions 

 

Endometrial thickening 

In 10-15% of patients, thickening of the endometrium (> 16 mm by ultrasound or MRI at end of 

treatment) was observed with ulipristal acetate by the end of the first 3-month treatment course. In 

subsequent treatment courses, endometrial thickening was less frequently observed (4.9% and 3.5% of 

patients by the end of second and fourth treatment course, respectively). The endometrial thickening  

reverses when treatment is stopped and menstrual periods resume. 



 

8 

 

In addition, reversible changes to the endometrium are denoted PAEC and are different from 

endometrial hyperplasia. If hysterectomy or endometrial biopsy specimens are sent for histology, then 

the pathologist should be informed that the patient has taken ulipristal acetate (see sections 4.4 

and 5.1). 

 

Hot flush 

Hot flushes were reported by 8.1% of patients but the rates varied across trials. In the active 

comparator controlled study the rates were 24% (10.5% moderate or severe) for ulipristal acetate and 

60.4% (39.6% moderate or severe) for leuprorelin-treated patients. In the placebo-controlled study, 

the rate of hot flushes was 1.0% for ulipristal acetate and 0% for placebo. In the first 3-month 

treament course of the two long term Phase III trials, the frequency was 5.3% and 5.8% for ulipristal 

acetate, respectively. 

 

Drug hypersensitivity 

Drug hypersensitivity symptoms such as generalised oedema, pruritus, rash, swelling face or urticaria 

were reported by 0.4% of patients in Phase III trials.  

 

Headache 

Mild or moderate severity headache was reported in 5.8% of patients. 

 

Ovarian cyst 

Functional ovarian cysts were observed during and after treatment in 1.0% of patients and in most of 

the cases spontaneously disappeared within a few weeks. 

 

Uterine haemorrhage 

Patients with heavy menstrual bleeding due to uterine fibroids are at risk of excessive bleeding, which 

may require surgical intervention. A few cases have been reported during ulipristal acetate treatment 

or within 2-3 months after ulipristal acetate treatment was stopped. 

 

Reporting of suspected adverse reactions 

Reporting 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. 

 

4.9 Overdose 

 

Experience with ulipristal acetate overdose is limited. 

Single doses up to 200 mg and daily doses of 50 mg for 10 consecutive days were administered to a 

limited number of subjects, and no severe or serious adverse reactions were reported. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, progesterone 

receptor modulators. ATC code: G03XB02. 
 

Ulipristal acetate is an orally-active synthetic selective progesterone receptor modulator characterised 

by a tissue-specific partial progesterone antagonist effect. 

 

Mechanism of action  

Ulipristal acetate exerts a direct effect on the endometrium. 

 



 

9 

Ulipristal acetate exerts a direct action on fibroids reducing their size through inhibition of cell 

proliferation and induction of apoptosis. 

 

Pharmacodynamic effects 

Endometrium 

When daily administration of a 5 mg dose is commenced during a menstrual cycle most subjects 

(including patients with myoma) will complete their first menstruation but will not menstruate again 

until after treatment is stopped. When ulipristal acetate treatment is stopped, menstrual cycles 

generally resume within 4 weeks. 

 

The direct action on the endometrium results in class-specific changes in histology termed PAEC. 

Typically, the histological appearance is an inactive and weakly proliferating epithelium associated 
with asymmetry of stromal and epithelial growth resulting in prominent cystically dilated glands with 

admixed oestrogen (mitotic) and progestin (secretory) epithelial effects. Such a pattern has been 

observed in approximately 60% of patients treated with ulipristal acetate for 3 months. These changes 

are reversible after treatment cessation. These changes should not be confused with endometrial 

hyperplasia. 

 

About 5% of patients of reproductive age experiencing heavy menstrual bleeding have an endometrial 

thickness of greater than 16 mm. In about 10-15% of patients treated with ulipristal acetate the 

endometrium may thicken (> 16 mm) during the first 3-month treatment course. In case of repeated 

treatment courses, endometrial thickening was less frequently observed (4.9% of patients after second 

treatment course and 3.5% after fourth treatment course). This thickening disappears after treatment is 

withdrawn and menstruation occurs. If endometrial thickness persists after return of menstruations 

during off-treatment periods or beyond 3 months following the end of treatment courses, it may need 

to be investigated as per usual clinical practice to exclude other underlying conditions. 

 

Pituitary 

A daily dose of ulipristal acetate 5 mg inhibits ovulation in the majority of patients as indicated by 

progesterone levels maintained at around 0.3 ng/ml. 

 

A daily dose of ulipristal acetate 5 mg partially suppresses FSH levels but serum oestradiol levels are 

maintained in the mid-follicular range in the majority of patients and are similar to levels in patients 

who received placebo. 

 

Ulipristal acetate does not affect serum levels of TSH, ACTH or prolactin. 

 

Clinical efficacy and safety 

Pre-operative use: 

The efficacy of fixed doses of ulipristal acetate 5 mg and 10 mg once daily was evaluated in two 

Phase 3 randomised, double-blind, 13 week studies recruiting patients with very heavy menstrual 

bleeding associated with uterine fibroids. Study 1 was double-blind placebo controlled. Patients in 

this study were required to be anaemic at Study entry (Hb < 10.2 g/dl) and all patients were to receive 

oral iron 80 mg Fe++ in addition to study medicinal product. Study 2 contained the active comparator, 

leuprorelin 3.75 mg given once per month by intramuscular injection. In Study 2, a double-dummy 

method was used to maintain the blind. In both studies menstrual blood loss was assessed using the 

Pictorial Bleeding Assessment Chart (PBAC). A PBAC >100 within the first 8 days of menses is 

considered to represent excessive menstrual blood loss. 

 

In study 1, a statistically significant difference was observed in reduction in menstrual blood loss in 

favour of the patients treated with ulipristal acetate compared to placebo (see Table 1 below), 

resulting in faster and more efficient correction of anaemia than iron alone. Likewise, patients treated 

with ulipristal acetate had a greater reduction in myoma size, as assessed by MRI. 

 



 

10 

In study 2, the reduction in menstrual blood loss was comparable for the patients treated with 

ulipristal acetate and the gonadotrophin releasing hormone-agonist (leuprorelin). Most patients treated 

with ulipristal acetate stopped bleeding within the first week of treatment (amenorrhea). 

The size of the three largest myomas was assessed by ultrasound at the end of treatment (Week 13) 

and for another 25 weeks without treatment in patients who did not have hysterectomy or 

myomectomy performed. Myoma size reduction was generally maintained during this follow-up 

period in patients originally treated with ulipristal acetate but some re-growth occurred in patients 

treated with leuprorelin. 

 

Table 1: Results of primary and selected secondary efficacy assessments in Phase III studies 

Parameter 

Study 1 

 

Study 2 

 

Placebo 

 

 

N=48 

Ulipristal 

acetate 

5 mg/day 

N=95 

Ulipristal 

acetate 

10 mg/day 

N=94 

Leuprorelin 

3.75 mg/ 

month 

N=93 

Ulipristal 

acetate 

5 mg/day 

N=93 

Ulipristal 

acetate 

10 mg/day 

N=95 

Menstrual 

bleeding 

 

Median PBAC at 

baseline 

 

Median change at 

week 13  

 

 

376 

 

 

-59 

 

 

386 

 

 

-329 

 

 

330 

 

 

-326 

 

 

297 

 

 

-274 

 

 

286 

 

 

-268 

 

 

271 

 

 

-268 

Patients in 

amenorrhea at 

week 13  

3  

(6.3%) 

69 

(73.4%)1 

76  

(81.7%)2 

74  

(80.4%) 

70 

(75.3%) 

85 

(89.5%) 

Patients whose 

menstrual 

bleeding became 

normal (PBAC < 

75) at week 13 

9 

(18.8%) 

86 

(91.5%)1 

86  

(92.5%)1 

82  

(89.1%) 

84 

(90.3%) 

93 

(97.9%) 

Median change in 

myoma volume 

from baseline to 

week 13a 

+3.0% -21.2%3 -12.3%4 -53.5% -35.6% -42.1% 

a In Study 1, change from baseline in total myoma volume was measured by MRI. In Study 2, change in the volume of the 

three largest myomas was measured by ultrasound. Bold values in shaded squares indicate that there was a significant 

difference in the comparisons between ulipristal acetate and the control. These were always in favour of ulipristal acetate. 

P values: 1 = <0.001, 2 = 0.037, 3= <0.002, 4 = <0.006. 

 

Repeated intermittent use: 

The efficacy of repeated treatment courses fixed doses of ulipristal acetate 5 mg or 10 mg once daily 

was evaluated in two Phase 3 studies assessing up to 4 intermittent 3-month treatment courses in 

patients with heavy menstrual bleeding associated with uterine fibroids. Study 3 was on open-label 

study assessing ulipristal acetate 10 mg, where each of the 3-month treatment was followed by 

10 days of double-blind treatment with progestin or placebo. Study 4 was a randomized, double-blind 

clinical study assessing ulipristal acetate 5 or 10 mg. 

 

Studies 3 and 4 showed efficacy in controlling uterine fibroid symptoms (e.g. uterine bleeding) and 

reducing fibroid size after 2 and 4 courses. 

In study 3, treatment efficacy has been shown over > 18 months of repeated intermittent treatment 

(4 courses of 10 mg once daily), 89.7% of patients were in amenorrhea at the end of the treatment 

course 4. 

In study 4, 61.9% and 72.7% of patients were in amenorrhea at the end of both treatment 

course 1 and 2 combined (5 mg dose and 10 mg dose, respectively, p=0.032); 48.7 % and 60.5 % were 



 

11 

in amenorrhea at the end of all four treatment courses combined (5 mg dose and 10 mg dose, 

respectively, p=0.027). At the end of treatment course 4, 158 (69.6%) subjects and 164 (74.5%) 

subjects were assessed as being in amenorrhea, in the 5 mg dose and 10 mg dose respectively 

(p=0.290). 

 

Table 2: Results of primary and selected secondary efficacy assessments in long term Phase III studies 

Parameter After treatment course 2 

(two times 3 months of treatment) 

After treatment course 4 

(four times 3 months of treatment) 

 Study 3a Study 4 Study 3 Study 4 

Patients starting 

treatment 

course 2 or 4 

10 mg/day 

N=132 

5 mg/day 

N=213 

10 mg/day 

N=207 

10 mg/day 

N=107 

5 mg/day 

N=178  

10 mg/day 

N=176 

Patients in 

amenorrheab,c 

N=131 N=205 N=197 N=107 N=227  N=220  

116  

(88.5%) 

152 

(74.1%) 

162 

(82.2%) 

96 

(89.7%) 

158 

(69.6%) 

164 

(74.5%) 

Patients with 

controlled 

bleedingb,c, d 

NA N=199 N=191 NA N=202 N=192 

175 

(87.9%) 

168 

(88.0%) 

148 

(73.3%) 

144 

(75.0%) 

Median change 

in myoma 

volume from 

baseline 

-63.2% -54.1% -58.0% -72.1% -71.8% -72.7% 

a Treatment course 2 assessment corresponds to Treatment course 2 plus one menstrual bleeding. 

b Patients with missing values were exluded from the analysis. 
c N and % include withdrawn patients  
d Controlled bleeding was defined as no episodes of heavy bleeding and a maximum of 8 days of bleeding (not including 

days of spotting) during the last 2 months of a treatment course. 

 

In all Phase III studies including repeated intermittent treatment studies, a total of 7 cases of 

hyperplasia were observed out of 789 patients with adequate biopsies (0.89%). The vast majority 

spontaneously reversed to normal endometrium after resumption of menstruation during the 

off-treatment period. The incidence of hyperplasia did not increase with repeated treatment courses, 

including data on 340 women who received up to 4 courses of ulipristal acetate 5 or 10 mg and 

limited data of 43 women who received up to 8 courses of ulipristal acetate 10 mg. The observed 

frequency is in line with control groups and prevalence reported in literature for symptomatic pre-

menopausal women of this age group (mean of 40 years). 

 

Paediatric population 

The European Medicines Agency has waived the obligation to submit the results of studies with 

Esmya in all subsets of the paediatric population in leiomyoma of uterus (see section 4.2 for 

information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

Following oral administration of a single dose of 5 or 10 mg, ulipristal acetate is rapidly absorbed, 

with a Cmax of 23.5 ± 14.2 ng/ml and 50.0 ± 34.4 ng/ml occurring approximately 1 h after ingestion, 

and with an AUC0-∞ of 61.3 ± 31.7 ng.h/ml and 134.0 ± 83.8 ng.h/ml, respectively. Ulipristal acetate 

is rapidly transformed into a pharmacologically active metabolite with a Cmax of 9.0 ± 4.4 ng/ml and 

20.6 ± 10.9 ng/ml also occurring approximately 1 h after ingestion, and with an AUC0-∞ of 

26.0 ± 12.0 ng.h/ml and 63.6 ± 30.1 ng.h/ml respectively. 

Administration of ulipristal acetate (30 mg tablet) together with a high-fat breakfast resulted in 

approximately 45% lower mean Cmax, a delayed tmax (from a median of 0.75 hours to 3 hours) and 25% 

higher mean AUC0-∞ compared with administration in the fasted state. Similar results were obtained 



 

12 

for the active mono-N-demethylated metabolite. This kinetic effect of food is not expected to be of 

clinical relevance for daily administration of ulipristal acetate tablets. 

 

Distribution 

Ulipristal acetate is highly bound (>98%) to plasma proteins, including albumin, alpha-l-acid 

glycoprotein, high density lipoprotein and low density lipoprotein. 

 

Ulipristal acetate and its active mono-N-demethylated metabolite are excreted in breast milk with a 

mean AUCt milk/plasma ratio of 0.74 ± 0.32 for ulipristal acetate. 

 

Biotransformation/Elimination 

Ulipristal acetate is readily converted to its mono-N-demethylated and subsequently to its 

di-N-demethylated metabolites. In vitro data indicate that this is predominantly mediated by the 

cytochrome P450 3A4 isoform (CYP3A4). The main route of elimination is through faeces and less 

than 10% is excreted in the urine. The terminal half-life of ulipristal acetate in plasma following a 

single dose of 5 or 10 mg is estimated to be about 38 hours, with a mean oral clearance (CL/F) of 

about 100 l/h. 

 

In vitro data indicate that ulipristal acetate and its active metabolite do not inhibit CYP1A2, 2A6, 

2C9, 2C19, 2D6, 2E1, and 3A4, or induce CYP1A2 at clinically relevant concentrations. 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 and its active metabolite are not P-gp (ABCB1) substrates. 

 

Special populations 

No pharmacokinetic studies with ulipristal acetate have been performed in women with impaired renal 

or hepatic function. Due to the CYP-mediated metabolism, hepatic impairment is expected to alter the 

elimination of ulipristal acetate, resulting in increased exposure. Esmya is contraindicated in patients 

with hepatic disorder (see section 4.3 and 4.4). 

 

5.3 Preclinical safety data 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, and genotoxicity.  

 

Most findings in general toxicity studies were related to its action on progesterone receptors (and at 

higher concentrations on glucocorticoid receptors), with antiprogesterone activity observed at 

exposures similar to therapeutic levels. In a 39-week study in cynomolgus monkeys, histological 

changes resembling PAEC were noted at low doses. 

 

Due to its mechanism of action, ulipristal acetate has an embryolethal effect in rats, rabbits (at 

repeated doses above 1 mg/kg), guinea pigs and in monkeys. The safety for a human embryo is 

unknown. At doses which were low enough to maintain gestation in the animal species, no teratogenic 

potential was observed. 

 

Reproduction studies performed in rats at doses giving exposure in the same range as the human dose 

have revealed no evidence of impaired fertility due to ulipristal acetate in treated animals or the 

offspring of treated females. 

 

Carcinogenicity studies (in rats and mice) showed that ulipristal acetate is not carcinogenic. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 



 

13 

 

Microcrystalline cellulose 

Mannitol 

Croscarmellose sodium 

Talc 

Magnesium stearate 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

3 years. 

 

6.4 Special precautions for storage 

 

Keep the blisters in the outer carton in order to protect from light. 

 

6.5 Nature and contents of container 
 

Alu/PVC/PE/PVDC or Alu/PVC/PVDC blister. 

Pack of 28, 30 and 84 tablets. 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Gedeon Richter Plc. 

Gyömrői út 19-21. 

1103 Budapest 

Hungary 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/750/001 

EU/1/12/750/002 

EU/1/12/750/003 

EU/1/12/750/004 

EU/1/12/750/005 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 23 February 2012 

Date of latest renewal: 14 November 2016 

 

 



 

14 

10. DATE OF REVISION OF THE TEXT 

 

DD/MM/YYYY 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



 

15 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 

 

 



 

16 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturers responsible for batch release 

 

Cenexi 

17, Rue de Pontoise 

FR-95520 Osny 

France 

 

Gedeon Richter Plc, 

1103 Budapest 

Gyömrői út 19-21 

Hungary 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic Safety Update Reports 
 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk Management Plan (RMP) 

 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as a result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

• Additional risk minimisation measures 
Prior to launch of the medicinal product in each Member State, the Marketing Authorisation Holder 

(MAH) shall agree the content and format of the educational material with the national competent 

authority. 

The MAH shall ensure that, at launch and thereafter, all prescribers of Esmya and pathologists who 

review samples from Esmya-treated patients, as well as patients treated with Esmya, are provided with 

educational material. 



 

17 

The educational material shall consist of the following: 

• Educational material for prescribers (gynaecologists) which contains: 

o Cover letter 

o SmPC 

o Physician’s guide to prescribing Esmya 

• Educational material for pathologists which contains 

o Pathologist’s guide 

o USB stick or CD ROM with images of digital specimens (digital library with high 

resolution images) 

o SmPC 

• Educational material for patients which contains 

o Patient card 

 

The educational material shall contain the following key elements: 

 

Physician’s guide to prescribing 

• detailed recommendations for management of endometrial thickening. 

• reminder of the effect of ulipristal acetate on the endometrium. 

• the need to inform the pathologist that patients were treated with Esmya if biopsy/surgical 

samples are to be sent for analysis. 

• the indications. 

• the posology: 5 mg tablet once daily for treatment courses of up to 3 months each. 

Treatments should only be initiated when menstruation has occurred: the first treatment 

course should start during the first week of menstruation, re-treatment courses should start at 

the earliest during the first week of the second menstruation following the previous treatment 

course completion. The treating physician should explain to the patient the requirement for 

treatment free intervals. 

• the contraindications of pregnancy and breastfeeding, genital bleeding of unknown aetiology 

or for reasons other than uterine fibroids, and uterine, cervical, ovarian or breast cancer as 

well as underlying hepatic disorder. 

• absence of safety data on the endometrium for continuous treatment longer than 3 months. 

• the need to investigate as per usual clinical practice persistence of endometrial thickening 

following treatment discontinuation and return of menstruation to exclude other underlying 

conditions. 

• recommendation of a periodic monitoring of the endometrium in case of repeated intermittent 

treatment. This includes annual ultrasound to be performed after resumption of menstruation 

during off-treatment period. If endometrial thickening is noted, which persists after return of 

menstruations during off-treatment periods or beyond 3 months following the end of 

treatment courses, and/or an altered bleeding pattern is noted, investigation including 

endometrial biopsy should be performed in order to exclude other underlying conditions, 

including endometrial malignancy. 

• baseline liver function tests are required before treatment initiation, and before each new 

treatment course. 

• patients with alanine transaminase (ALT) or aspartate aminotransferase (AST) > 2 x ULN 

(isolated or in combination with bilirubin >2 x ULN) must not be treated. 

• liver function must be monitored monthly during the first 2 treatment courses, and thereafter 

when clinically indicated. 

• treatment must be stopped if the patient develops ALT or AST > 3 x ULN. 

• if a patient during treatment shows signs or symptoms compatible with liver injury, treatment 

should be stopped, and the patient should be investigated immediately, and liver function 

tests performed. 

• in addition, liver testing should be performed within 2-4 weeks after treatment has stopped. 

 

 

 



 

18 

Educational material for pathologists 

• key effects of Esmya on Progesterone Receptor Modulator Associated Endometrial Changes 

(PAEC) and how they differ from those of unopposed oestrogen. 

• the differential diagnosis between PAEC, unopposed oestrogen and endometrial hyperplasia. 

 

Patient card 

• inform the patients about potential adverse reactions related to liver that could be caused by 

the use of Esmya. 

• inform the patients on the need to warn their physicians on any liver problems they may 

have.  

• inform the patients not to take Esmya in case of liver problems. 

• inform the patients about the need for monitoring of liver function before starting each 

treatment course, monthly during treatment and within a few weeks after the treatment has 

stopped. 

• inform the patients about the symptoms and signs of possible liver injury so that they are 

aware of situations in which they should stop treatment and contact a physician in a timely 

manner. 



 

19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

 

 



 

20 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



 

21 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Esmya 5 mg tablets 

Ulipristal acetate 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg of ulipristal acetate. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 tablets  

30 tablets 

84 tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Keep the blisters in the outer carton in order to protect from light. 

 

 



 

22 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Gedeon Richter Plc. 

Gyömrői út 19-21. 

1103 Budapest 

Hungary 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/12/750/001 28 tablets 

EU/1/12/750/002 84 tablets 

EU/1/12/750/003 30 tablets 

EU/1/12/750/004 28 tablets 

EU/1/12/750/005 84 tablets 

 

 

13. BATCH NUMBER 

 

Batch 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Esmya 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included.  

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN:



 

23 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Esmya 5 mg tablets 

Ulipristal acetate 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Gedeon Richter 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Batch 

 

 

5. OTHER 

 

 



 

24 

 

ESMYA 5mg TABLETS 

 

PATIENT CARD 

 

 

WHAT YOU NEED TO KNOW BEFORE USE? 

 

Esmya can cause side effects although not everybody gets them. One possible side effect is serious 

damage to your liver. 

This card provides information on blood tests you will need throughout treatment and on what you 

should do if liver side effects occur. 

 

Do not take Esmya if you have liver problems.Tell your doctor if you know that you have problems 

with your liver or if you have any doubts about the condition of your liver. 

 

 

WHAT TO DO BEFORE DURING AND AFTER YOUR TREATMENT? 

 

Have regular blood tests 

 

You need blood tests before starting each treatment course to find out how your liver is working. 

Depending on the result of these tests, the doctor will decide if treatment with Esmya is suitable for 

you. 

 

During treatment with Esmya, your doctor will carry out regular blood tests to check your liver 

function. These tests need to happen every month, including a few weeks after you finish a course of 

treatment (see schedule below). These blood tests will inform the doctor of the functioning of your 

liver and are vital when monitoring your treatment. 

  

 

THE TABLE BELOW HELPS YOU TO TRACK YOUR BLOOD TESTS: 

 

 DATE 

1st TEST (before treatment start)  

Start of treatment  

2nd TEST (4 weeks after starting treatment)  

3rd TEST (8 weeks after starting treatment)  

4th TEST (12 weeks after starting treatment)  

5th TEST (2- 4 weeks after stopping Esmya treatment) 

 

 

 

 

SIGNS AND SYMPTOMS OF POSSIBLE LIVER PROBLEMS 

Stop treatment and contact a doctor right away if you observe any of the following signs or symptoms: 

 

• fatigue, severe tiredness 

• yellow skin/eyes 

• darkening of the urine 

• pain in the upper right stomach 

• itching 



 

25 

• nausea (feeling sick) 

• vomiting 

 

The doctor should check your liver immediately and decide if you can continue the treatment. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



 

26 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

27 

Package leaflet: Information for the user 

 

Esmya 5 mg tablets 

Ulipristal acetate 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Esmya is and what it is used for 

2. What you need to know before you take Esmya 

3. How to take Esmya 

4. Possible side effects 

5. How to store Esmya 

6. Contents of the pack and other information 

 

 

1. What Esmya is and what it is used for 
 

Esmya contains the active substance ulipristal acetate. It is used to treat moderate to severe symptoms 

of uterine fibroids (commonly known as myomas), which are non-cancerous tumours of the uterus 

(womb). 

Esmya is used in adult women (over 18 years of age) before they reach the menopause. 

 

In some women, uterine fibroids may cause heavy menstrual bleeding (your ‘period’), pelvic pain 

(discomfort in the belly) and create pressure on other organs. 

 

This medicine acts by modifying the activity of progesterone, a naturally occuring hormone in the 

body. It is used either before an operation of your fibroids or for long term treatment of your fibroids 

to reduce their size, to stop or reduce bleeding and to increase your red blood cell count. 

 

 

2. What you need to know before you take Esmya 
 

You should know that most women have no menstrual bleeding (period) during the treatment and for 

a few weeks afterwards.  

 

Do not take Esmya 

- if you are allergic to ulipristal acetate or any of the other ingredients of Esmya (listed in 

section 6). 

- if you have an underlying hepatic disorder. 
- if you are pregnant or if you are breastfeeding. 

- if you have vaginal bleeding not caused by uterine fibroids. 

- if you have cancer of the uterus (womb), cervix (the neck of the womb), ovary or breast. 

 

Warnings and precautions 

- Before you start treatment with Esmya blood tests will be undertaken to find out how well your 
liver is working. Depending on the result of these tests your doctor will decide if treatment with 

Esmya is suitable for you. These tests will be repeated monthly for the first 2 treatment courses. 

For further treatment courses, your liver will be checked once before each new treatment course 



 

28 

and if you experience any of the symptoms described below. In addition, an additional check of 

your liver 2-4 weeks after your treatment has stopped should be done.  

If during the treatment you experience any liver related signs such as feeling of being sick 

(nausea or vomiting), fatigue, severe tiredness, jaundice (yellowing of the eyes or skin), dark 

urine, itching or upper stomach ache, you should stop treatment and immediately contact a 

doctor, who will check the functioning of your liver and decide if you can continue the 

treatment. 

- If you are currently taking hormonal contraception (for example birth control pills) (see “Other 

medicines and Esmya”) you should use an alternative reliable barrier contraceptive method 

(such as a condom) while taking Esmya. 

- If you have liver or kidney disease tell your doctor or pharmacist before taking Esmya. 

- If you suffer from severe asthma, treatment with Esmya may not be suitable for you. You 

should discuss this with your doctor. 

 

Treatment with Esmya usually leads to a significant reduction or may even stop your menstrual 

bleeding (your ‘period’) within the first 10 days of treatment. However, if you continue to experience 

excessive bleeding tell your doctor. 

 

Your period should generally return within 4 weeks after treatment with Esmya is stopped. The lining 

of the uterus may thicken or change as a result of taking Esmya. These changes return to normal after 

treatment is stopped and your periods restart. 

 

Children and adolescents 

Esmya should not be taken by children under 18 years of age since safety and efficacy of ulipristal 

acetate has not been established in this age group. 

 

Other medicines and Esmya 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Tell your doctor or pharmacist if you are taking any of the medicines listed below, as these medicines 

can affect Esmya or be affected by Esmya: 

- Certain medicines which are used to treat the heart (e.g. digoxin). 

- Certain medicines used to prevent strokes and blood clots (e.g. dabigatran etexilate). 

- Certain medicines used to treat epilepsy (e.g. phenytoin, fosphenytoin, phenobarbital, 

carbamazepine, oxcarbazepine, primidone). 

- Certain medicines used to treat HIV infection (e.g. ritonavir, efavirenz, nevirapine). 

- Medicines used to treat certain bacterial infections (e.g. rifampicin, telithromycin, 

clarithromycin, erythromycin, rifabutin). 

- Certain medicines to treat fungal infections (e.g. ketoconazole (except shampoo), itraconazole). 

- Herbal remedies containing St John’s wort (Hypericum perforatum) used for depression or 

anxiety. 

- Certain medicines used to treat depression (e.g. nefazodone). 

- Certain medicines used to treat hypertension (e.g. verapamil). 

 

Esmya is likely to make some hormonal contraceptives less effective. In addition, hormonal 

contraceptives and progestagens (e.g. norethindrone or levonorgestrel) are also likely to make Esmya 

less effective. Therefore, hormonal contraceptives are not recommended and you should use an 

alternative reliable barrier contraceptive method, such as a condom, during Esmya treatment. 

 

Esmya with food and drink 

You should avoid drinking grapefruit juice while on treatment with Esmya. 

 

Pregnancy and breastfeeding 

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 



 

29 

 

Do not take Esmya if you are pregnant. Treatment whilst pregnant might affect your pregnancy (it is 

not known if Esmya might harm your baby or whether can cause miscarriage). If you do become 

pregnant during Esmya treatment, you should stop taking Esmya immediately and contact your doctor 

or pharmacist. 

 

Esmya is likely to make some hormonal contraceptives less effective (see “Other medicines and 

Esmya”). 

Esmya passes into the breast milk. Therefore, do not breast-feed your baby while taking Esmya. 

 

Driving and using machines 

Esmya may cause mild dizziness (see section 4 “Possible side effects”). Do not drive or use machines 

if you experience these symptoms. 

 

 

3. How to take Esmya 
 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

The recommended dose is one 5 mg tablet per day, for treatment courses of up to 3 months each.. If 

you have been prescribed several courses of Esmya 3-month treatment, you should start each course at 

the earliest during the second menstrual period following the previous treatment completion. 

You should always start taking Esmya within the first week of your menstrual period. 

The tablet should be swallowed with water and may be taken with or without food. 

 

If you take more Esmya than you should 

Experience with Esmya when several doses are taken at once is limited. There have been no reports of 

serious harmful effects from taking several doses of this medicine at once. You should nonetheless 

ask your doctor or pharmacist for advice if you take more Esmya than you should. 

 

If you forget to take Esmya 

If you miss a dose by less than 12 hours, take it as soon as you remember. If you miss a dose by more 

than 12 hours, skip the missed tablet and take only a single tablet as usual. Do not take a double dose 

to make up for a forgotten tablet. 

 

If you stop taking Esmya 

Esmya is to be taken daily during treatment courses of up to 3 months continuously. During each 

course of treatment, do not stop taking your tablets without the advice of your doctor even if you feel 

better, as symptoms may re-occur later. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Stop using Esmya and immediately contact a doctor if you experience any of the following symptoms:  

- swelling of face, tongue or throat; difficulty swallowing; hives and breathing difficulties. These 

are possible symptoms of angioedema (frequency not known). 

- nausea or vomiting, severe tiredness, jaundice (yellowing of the eyes or skin), dark urine, 
itching or upper stomach ache. These symptoms may be signs of liver injury (frequency not 

known). See also section 2 Warnings and precautions. 

 



 

30 

Very common (may affect more than 1 in 10 people) side effects: 

- reduction or absence of menstrual bleeding (amenorrhea) 

- thickening of the lining of the womb (endometrial thickening). 

 

Common (may affect up to 1 in 10 people) side effects: 

- headache 

- spinning sensation (vertigo) 

- stomach ache, feeling sick (nausea) 

- acne 

- muscle and bone (musculoskeletal) pain 

- sac of fluid within the ovaries (ovarian cyst), breast tenderness/pain, lower abdominal (pelvic) 

pain, hot flushes 

- tiredness (fatigue) 

- weight increase. 

 

Uncommon (may affect up to 1 in 100 people) side effects: 

- drug allergy 

- anxiety 

- mood swings 

- dizziness 

- dry mouth, constipation 

- hair loss, dry skin, increased sweating 

- back pain 

- leakage of urine 

- bleeding from the womb (uterine bleeding), vaginal discharge, abnormal vaginal bleeding, 

breast discomfort 

- swelling due to fluid retention (oedema) 

- extreme tiredness (asthenia) 

- increase in blood cholesterol seen in blood tests, increase in blood fats (triglycerides) seen in 

blood tests. 

 

Rare (may affect up to 1 in 1,000 people) side effects: 

- nosebleed 

- indigestion, bloating 

- break of sac of fluid within the ovaries (ovarian cyst ruptured) 

- breast swelling. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety 

of this medicine. 

 

 

5. How to store Esmya 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the carton and on the blister after 

EXP. The expiry date refers to the last day of that month. 

 

Keep the blister in the outer carton in order to protect from light. 

 

Do not throw away via wastewater or household waste. Ask your pharmacist how to throw away 

medicines you no longer use. These measures will help protect the environment. 

 



 

31 

 

6. Contents of the pack and other information 

 

What Esmya contains 

- The active substance is ulipristal acetate. One tablet contains 5 mg of ulipristal acetate. 

- The other ingredients are microcrystalline cellulose, mannitol, croscarmellose sodium, talc and 

magnesium stearate. 

 

What Esmya looks like and contents of the pack 

Esmya is white to off-white, round curved tablet of 7 mm engraved with code “ES5” on one face. 

It is available in Alu/PVC/PE/PVDC blisters in cartons containing 28, 30 and 84 tablets or 

Alu/PVC/PVDC blisters in cartons containing 28 and 84 tablets. 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 

Gedeon Richter Plc. 

Gyömrői út 19-21. 

1103 Budapest 

Hungary 

 

Manufacturer 

Cenexi 

17 rue de Pontoise 

F-95520 Osny 

France 

 

Gedeon Richter Plc. 

Gyömrői út 19-21. 

1103 Budapest 

Hungary 

 

This leaflet was last revised in  

 

Other sources of information  

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET