Travoprost

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 Izba

Assessment report for Izba (travoprost) 19 December 2013, EMA/13480/2014.

Hazard

Persistence: No data.

Bioaccumulation: Log K_ow = 4.483. "However, the study that ascertained this value was not carried out according to the criteria set out in the relevant OECD Guideline. Therefore, the log K_ow value for travoprost of 4.483 as determined in this study is questionable. In order to conclude on the exact log K_ow, its value should be determined strictly according to the guideline of the method chosen."

Toxicity: No data.

Risk

PEC = 0.009 microg/L. "As the PEC_surfacewater value is below the 0.01 μg/L action limit value, a Phase II environmental effect analysis is not needed. Travoprost is considered unlikely to represent a risk for the environment following its prescribed use and no further action is required under the Committee for Medicinal Products for Human Use (CHMP) “Guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/4447/00)”.

Conclusion

"If the log K_ow value obtained for the product would be higher than 4.5, according to “Guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/4447/00)” and “Questions and answers on 'Guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/44609/2010)”, travoprost should be screened by the MAH (marketing authorisation holder, ed. note) in a step-wise procedure for persistence, bioaccumulation and toxicity." No information about travoprost addressing this has been found on the EMA's website. A question about whether new data has been received by the authority was emailed to the Swedish Medical Products Agency 2020-09-07. See the answer in the next paragraph.

The background of the text in the SPC for Izba

According to an e-mail from the Swedish Medical Products Agency 2020-09-07, no new data has been received, but the issue has been discussed in Worksharing procedure EMEA/H/C/WS1385 and the MAH reasoned as follows:

“According to the REACH guidance on PBT assessment (Guidance on information requirements and chemical safety assessment. Part C: PBT/vPvB Assessment. Version 3.0. June 2017), the applicant may choose to treat the substance ‘as if it is a PBT or vPvB’ substance on the basis of the screening assessment (see chapter C.4.2. Assessment). Only ‘if the registrant decides to further evaluate the properties of the substance’, a full assessment for PBT properties with definitive tests is required. The applicant believes that the available information is sufficient to perform the PBT assessment: the screening criteria for P and B are met as required, and criteria for toxicity is met based on the outcome of mammalian toxicity studies. Consequently, based on the screening criteria for P and B and definitive assessment criteria for T, the applicant chooses to treat the substance as PBT substance and to abstain from a definitive PBT assessment, including a definitive study on Persistence (Study on Transformation in aquatic sediment systems according to the Organization for Economic Co-operation and Development [OECD] 308). Also, in line with the ERA guidance, the requirement to perform an OECD 308 study for substances that are not readily biodegradable is stated only for Phase II Fate and Exposure Assessment. As travoprost clearly remains below the trigger level for a Phase II Fate and Exposure Assessment, this API does not fall under the requirement to perform a study following OECD 308.

The applicant accepts the PBT hazard label as a conservative, worst case hazard statement, that results in an addition of this hazard label to the SmPC.”

The result was that the SPC for Izba was updated on 26 July 2018 with the information in section 5.3 but also in section 6.6: "It should be noted that travoprost is considered a PBT substance (see section 5.3)."

Assessment report Travatan

Assessment report for Travatan (travoprost) 20 November 2014, EMA/CHMP/673466/2014, type II variation for an extended indication.

"The MAH stated that the addition of the new paediatric population is not likely to cause a significant increase of the overall Predicted Environmental Concentration (PEC) in the environment. However, the results of the persistence, bioaccumulation and toxicity (PBT) screening test (Log_Kow Assessment report EMA/CHMP/673466/2014 Page 8/39 determined experimentally by slow-stirring method) need to be submitted. Furthermore, if the value obtained for the product would be higher than 4.5, Travoprost should be screened by the Applicant in a step-wise procedure for persistence, bioaccumulation and toxicity. The CHMP recommended that an updated ERA is submitted." No such data have been found in searches on the EMA website (2025-05-13).

Fass environmental information

Fass environmental information for Izba (travoprost) from Novartis (accessed on 2025-05-13).

Hazard

Persistence: 3–4%, not readily biodegradable (OECD301B). Travoprost is potentially persistent.

Bioaccumulation: log K_ow = 4.647 (OECD123). Travoprost has high potential for bioaccumulation.

Toxicity: No data.

Risk

PEC = 0.04 ng/L (year 2022). Risk of environmental impact of travoprost cannot be excluded, since there is not sufficient ecotoxicity data available.