In accordance with paragraph 8 of Section IV of the Procedure for Expert Evaluation, the applicant must amend the instructions for medical use of the medicinal product upon receipt of new data, including bringing the instructions for medical use into line with the approved instructions for medical use of the original (reference) medicinal product, and ensure that the information on the medicinal product corresponds to current scientific knowledge.
The European Medicines Agency (EMA) published the minutes of the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of July 7 – 10, 2025. Based on the results of the meeting, a decision was made on the need to introduce safety-related changes to the registration materials/instructions for medical use of medicinal products containing bosentan.
Bosentan – STAYVEER; TRACLEER – PSUSA/00000425/20241
Bosentan (bosentan) is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension and for reducing the number of new ulcers of the extremities (fingers and toes) in patients with systemic sclerosis and with progressive ulcerative lesions of the extremities (fingers and toes).
Based on the evaluation of periodic safety update reports (PSURs), the PRAC reviewed the benefit/risk balance of the medicinal products STAYVEER (bosentan), TRACLEER (bosentan), and medicinal products containing bosentan and gave the following recommendations.
Summary of recommendations and conclusions
- On the basis of the analysis of safety and efficacy data, it has been established that the benefit/risk balance of medicinal products containing bosentan (bosentan), for the approved indications remains unchanged.
- Nevertheless, the instructions for medical use should be updated by adding autoimmune hepatitis as a warning and as an adverse reaction with the frequency “rare”. Thus, the existing provisions of the instructions for medical use should be amended1.
- In the next PSUR, registration certificate holders (RCHs) should continue to monitor cases of pulmonary edema in patients with chronic thromboembolic pulmonary hypertension or other postcapillary conditions, except pulmonary veno-occlusive disease (PVOD), and consider any new relevant information.
- RCHs that have a Risk Management Plan (RMP) must remove the following important risks from the list of safety concerns: decreased hemoglobin concentration, decreased sperm count, pulmonary edema associated with pulmonary veno-occlusive disease, interaction with substrates, inducers, or inhibitors of cytochrome P450 isoenzymes CYP3A4 and CYP2C9, testicular dysfunction and male infertility, and respiratory tract infections in children, as well as “missing information” on the use of bosentan together with the addition of sildenafil in children and use in children with renal impairment, at the next RMP update, which must be submitted as part of a future regulatory procedure concerning the RMP.
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1 Update of the “Special precautions for use” and “Adverse reactions” sections of the instructions for medical use. The risk assessment report and the PRAC recommendation are forwarded to the CHMP for adoption of a decision.
Comprehensive and up-to-date information on an individual medicinal product (summary of product characteristics, post-registration procedural steps, RMP summary, additional risk minimization measures, etc.) registered through the centralized procedure can be found in the Human medicines European public assessment report (EPAR) on the EMA website.
Перелік лікарських засобів, що містить бозентан (bosentan) та дозволені до медичного застосування в Україні (за даними Державного реєстру лікарських засобів станом на 07.11.2025).
TO SUBMIT THE CORRESPONDING APPLICATION FOR AMENDMENTS TO THE REGISTRATION MATERIALS, THE APPLICANT MUST USE THE ORIGINAL TEXT POSTED AT THE LINK, FOR ANALYSIS OF THE PUBLISHED INFORMATION:
