Macitentan
Summary
Persistence. The potential for persistence of macitentan cannot be excluded, due to lack of data
Bioaccumulation. Macitentan has low potential for bioaccumulation.
Toxicity. It cannot be excluded that macitentan is toxic, due to lack of data.
Risk. Risk of environmental impact of macitentan cannot be excluded, since no ecotoxicity data are available.
This summary information comes from assessment report and fass.se.
Detailed information
General information about assessment reports
Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data are available in the public assessment report (PAR/EPAR for centrally approved medicines). Environmental considerations are not included in the benefit-risk assessment for human medicines. If new data emerge after approval that necessitate an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the regulatory authority.
The PEC (predicted environmental concentration) values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, as well as possibly other products from the same company, not all medicinal products containing the same active substance.
Assessment report Opsumit
Assessment report for Opsumit (macitentan) for extension application to introduce a new pharmaceutical form associated with new strengths (1 and 2.5 mg dispersible tablet) grouped with an extension of indication, Janssen-Cilag, 25 July 2024, EMA/389480/2024.
Hazard
Persistence: No data.
Bioaccumulation: Log Kow 3.91 (OECD 123).
Toxicity: No data.
Risk
PECsw, refined = 0.0008 microg/L. Conclusion: ≥ 0.01 threshold: N.
Macitentan has only undergone a phase I study in accordance with regulatory requirements for environmental risk assessments (Guideline on the environmental risk assessment of medicinal products for human use, EMEA/CHMP/SWP/4447/00 Rev. 1- Corr.) A phase I study includes data on bioaccumulation and an estimation of the environmental concentration of macitentan (PECSurface water). If the specified threshold values are not exceeded, the company is not required to conduct a Phase II study, which includes data on toxicity, persistence, and risk assessment based on PEC/PNEC.
Assessment report Yuvanci
Assessment report for macitentan from Yuvanci (macitentan, tadalafil), Janssen-Cilag, 25 July 2024, EMA/CHMP/332056/2024.
"The doses of macitentan and tadalafil in the proposed FDC tablet are identical to the recommended doses in currently approved single agent products for the treatment of PAH. Since the FDC is not to be administered at higher dosage levels, or for different indications, significant increase in environmental exposure is not anticipated." FDC = Fixed-Dose Combination. PAH = Pulmonary Arterial Hypertension.
Fass environmental information
Fass environmental information for Opsumit from Janssen-Cilag (retrieved on 2025-10-28).
Hazard
Persistence: No data.
Bioaccumulation: According to available data, macitentan has a low potential for bioaccumulation. Log D (pH 7.4): 2.13 BCF (pH 7.4): 8.44.
Toxicity: No data.
Risk
PEC/PNEC is based on sales data in Sweden in year 2023.
PEC = 0.0002719998 microg/L.
Risk of environmental impact of macitentan cannot be excluded, since no ecotoxicity data are available.
References
- European Medicines Agency. European public assessment report (EPAR) for Opsumit (macitentan), Janssen-Cilag, 25 July 2024, EMA/389480/2024.
- European Medicines Agency. European public assessment report (EPAR) for Yuvanci (macitentan, tadalafil), Janssen-Cilag, 25 July 2024, EMA/CHMP/332056/2024.
- Fass.se för vårdpersonal.
Author: Health and Medical Care Administration, Region Stockholm