Ulipristal Acetate Gedeon Richter

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Ulipristal Acetate Gedeon Richter 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 
 
Ulipristal Acetate Gedeon Richter 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). 
 
 
 



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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. 
 
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. 



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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, 
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 



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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). 
 
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 



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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. 
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). 
 



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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. 



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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. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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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. 
 



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



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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 
Ulipristal Acetate Gedeon Richter 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 
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. 



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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. Ulipristal Acetate Gedeon Richter 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 
 
Microcrystalline cellulose 



13 

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 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Gedeon Richter Plc. 
Gyömrői út 19-21. 
1103 Budapest 
Hungary 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1309/001 
EU/1/18/1309/002 
EU/1/18/1309/003 
EU/1/18/1309/004 
EU/1/18/1309/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: DD month YYYY 
Date of latest renewal: DD month YYYY 
 
 



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 

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 Ulipristal Acetate Gedeon 
Richter and pathologists who review samples from Ulipristal Acetate Gedeon Richter-treated patients, 
as well as patients treated with Ulipristal Acetate Gedeon Richter, 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 Ulipristal Acetate Gedeon Richter 

• 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 Ulipristal Acetate Gedeon 

Richter 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. 
 

Educational material for pathologists 



18 

• key effects of Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter. 

• inform the patients on the need to warn their physicians on any liver problems they may have.  
• inform the patients not to take Ulipristal Acetate Gedeon Richter 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 
 
Ulipristal Acetate Gedeon Richter 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/1/18/1309/001 28 tablets 
EU/1/18/1309/002 84 tablets 
EU/1/18/1309/003 30 tablets 
EU/1/18/1309/004 28 tablets 
EU/1/18/1309/005 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 
 
Ulipristal Acetate Gedeon Richter 
 
 
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 
 
Ulipristal Acetate Gedeon Richter 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 

 
ULIPRISTAL ACETATE GEDEON RICHTER 5 mg TABLETS 
 
PATIENT CARD 
 
 
WHAT YOU NEED TO KNOW BEFORE USE? 
 
Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate 
Gedeon Richter is suitable for you. 
 
During treatment with Ulipristal Acetate Gedeon Richter, 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 Ulipristal Acetate 
Gedeon Richter 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 



25 

• itching 
• 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 
 

Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter is and what it is used for 
2. What you need to know before you take Ulipristal Acetate Gedeon Richter 
3. How to take Ulipristal Acetate Gedeon Richter 
4. Possible side effects 
5. How to store Ulipristal Acetate Gedeon Richter 
6. Contents of the pack and other information 
 
 
1. What Ulipristal Acetate Gedeon Richter is and what it is used for 
 
Ulipristal Acetate Gedeon Richter 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). 
Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter 
 
You should know that most women have no menstrual bleeding (period) during the treatment and for a 
few weeks afterwards.  
 
Do not take Ulipristal Acetate Gedeon Richter 
- if you are allergic to ulipristal acetate or any of the other ingredients of Ulipristal Acetate 

Gedeon Richter (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 Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter is suitable for you. These tests 



28 

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 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 Ulipristal Acetate Gedeon Richter”) you should use an alternative reliable barrier 
contraceptive method (such as a condom) while taking Ulipristal Acetate Gedeon Richter. 

- If you have liver or kidney disease tell your doctor or pharmacist before taking Ulipristal 
Acetate Gedeon Richter. 

- If you suffer from severe asthma, treatment with Ulipristal Acetate Gedeon Richter may not be 
suitable for you. You should discuss this with your doctor. 

 
Treatment with Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon 
Richter is stopped. The lining of the uterus may thicken or change as a result of taking Ulipristal 
Acetate Gedeon Richter. These changes return to normal after treatment is stopped and your periods 
restart. 
 
Children and adolescents 
Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter 
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 Ulipristal Acetate Gedeon Richter or be affected by Ulipristal Acetate Gedeon Richter: 
- 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). 

 
Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter less effective. Therefore, hormonal contraceptives 
are not recommended and you should use an alternative reliable barrier contraceptive method, such as 
a condom, during Ulipristal Acetate Gedeon Richter treatment. 
 
Ulipristal Acetate Gedeon Richter with food and drink 



29 

You should avoid drinking grapefruit juice while on treatment with Ulipristal Acetate Gedeon Richter. 
 
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. 
 
Do not take Ulipristal Acetate Gedeon Richter if you are pregnant. Treatment whilst pregnant might 
affect your pregnancy (it is not known if Ulipristal Acetate Gedeon Richter might harm your baby or 
whether can cause miscarriage). If you do become pregnant during Ulipristal Acetate Gedeon Richter 
treatment, you should stop taking Ulipristal Acetate Gedeon Richter immediately and contact your 
doctor or pharmacist. 
 
Ulipristal Acetate Gedeon Richter is likely to make some hormonal contraceptives less effective (see 
“Other medicines and Ulipristal Acetate Gedeon Richter”). 
Ulipristal Acetate Gedeon Richter passes into the breast milk. Therefore, do not breast-feed your baby 
while taking Ulipristal Acetate Gedeon Richter. 
 
Driving and using machines 
Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter 
 
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 Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter than you should 
Experience with Ulipristal Acetate Gedeon Richter 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 Ulipristal 
Acetate Gedeon Richter than you should. 
 
If you forget to take Ulipristal Acetate Gedeon Richter 
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 Ulipristal Acetate Gedeon Richter 
Ulipristal Acetate Gedeon  Richter 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. 



30 

 
Stop using Ulipristal Acetate Gedeon Richter 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. 

 
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 Ulipristal Acetate Gedeon Richter 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


31 

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. 
 
 
6. Contents of the pack and other information 
 
What Ulipristal Acetate Gedeon Richter 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 Ulipristal Acetate Gedeon Richter looks like and contents of the pack 
Ulipristal Acetate Gedeon Richter 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 MM/YYYY 
 
Other sources of information  
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 

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