Disclaimer

You are now leaving www.esmya.com. Links to other websites are provided as a resource to our visitors.

Gedeon Richter accepts no responsibility for the content of other websites.

Esmya® Safety & Tolerability

Esmya® is well-tolerated over the long term

The safety profile of Esmya® is supported by extensive clinical studies and real-life experience. The vast majority of adverse events during intermittent and pre-operative therapy with Esmya® were mild to moderate and resolved spontaneously 7,44.

Menopausal-like adverse events decreased in frequency during intermittent therapy.
Hot flushes decreased from 5.7% to 2.8% between the first and fourth courses7.

References

  • 480 Reference 7 - Donnez J, et al. Fertil Steril 2016;105(1):165-173. e4 [PEARL IV PART 2]
  • 2908 Reference 44 – Donnez J, et al. Long-term treatment of uterine fibroids with Ulipristal Acetate. Fertil Steril 2014;101(6):1565-1573. [PEARL III]

Esmya® contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the Smpc.
  • Pregnancy and breastfeeding.
  • Genital bleeding of unknown aetiology or for reasons other than uterine fibroids.
  • Uterine, cervical, ovarian or breast cancer.
  • Underlying hepatic disorder.

In order to ensure that patients are adequately informed on the possible risks of liver injury and the implemented risk minimisation measures, a patient card is to be provided in each package of Esmya. Click here to download it.

Reference 3 – Esmya® SmPC. May 2018.

Esmya® and liver function tests

  • Liver function tests must be performed before starting treatment. Treatment must not be initiated if transaminases (ALT or AST) exceed 2 × ULN (isolated or in combination with bilirubin >2 × ULN)1
  • During treatment, liver function tests must be performed monthly during the first two treatment courses. For further treatment courses, liver function must be tested once before each new treatment course and when clinically indicated1
  • In addition liver testing should be performed 2–4 weeks after treatment has stopped1

In order to ensure that patients are adequately informed on the possible risks of liver injury and the implemented risk minimisation measures, a patient card is to be provided in each package of Esmya. Click here to download it.

ALT, alanine transaminase; AST, aspartate aminotransferase; ULN, upper limit of normal
1. ESMYA®. Summary of Product Characteristics. May 2018; 2. Donnez J, et al. Fertil Steril 2016;105:165–73.e4

Esmya® Adverse Reactions

When comparing repeated treatment courses, overall adverse reactions rate was lower in subsequent treatment courses than during the first course 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 occurrence).

Tabulated list of adverse reactions3

 

System Organ Class

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

   

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

When comparing repeated treatment courses, overall adverse reactions rate was lower in subsequent treatment courses than during the first course 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 occurrence).

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 reverse after treatment cessation.

These histological changes are denoted as “Progesterone Receptor Modulator Associated Endometrial Changes” (PAEC) and should not be mistaken for endometrial hyperplasia. Evidence indicates PRM-Associated Endometrial Changes (PAEC) are harmless and quickly reversible41

See EU SmPC for further guidance on how to monitor the endometrium.

 

Endometrial findings

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. 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).

 

PAEC viewer

Educational material to inform gynaecologists and pathologists about the appearance of the endometrium when PAEC changes occur and how they are best managed can be found at the following sources:

https://esmya.com/educationals-resources/

If sending tissue specimens to your local pathology departments, it is advisable to inform them that the patient has been taking Esmya® as this will indicate that PAEC or endometrial thickening may be observed.

 

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.

 

 

 

References

  • 2911 Reference 41 – Mutter GL., et al. “The spectrum of endometrial pathology induced by progesterone receptor modulators.” Mod Pathol 2008; 21: 591-598
7fc16655c1
/wp-admin/options-general.php?page=emc2-popup-disclaimer%2Femc2pdc-admin.php
65dc6cecd1
2090
1
Accept
Decline
http://fibroidsconnect.com/
1

For Healthcare Professionals only

This information contained in this website was specifically created for healthcare professionals. Please tick here to confirm that you are a licensed healthcare professional.
Registration conditions of ESMYA® could differ in each country, please refer to your local regulations for more information.

Accept Decline