Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Travoprost

Information

This summary information is from the SPC (Summary of Product Characteristics) for Izba (travoprost) section 5.3 (downloaded 2020-09-08).

"Travoprost is considered a persistent, bioaccumulative and toxic (PBT) substance. Hence, despite the very small amounts of travoprost used by patients in eye drops, a risk to the environment cannot be excluded."

Detailed information

Assessment report

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

Hazard

Persistence: No data.

Bioaccumulation: Log Kow = 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 Kow value for travoprost of 4.483 as determined in this study is questionable. In order to conclude on the exact log Kow, 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 PECsurfacewater 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 Kow 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, red. anm.) 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)."

Fass environmental information

Fass environmental information for Izba (travoprost) from Novartis (downloade 2020-09-07).

Hazard

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

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

Toxicity: No data.

Risk

PEC = 0.0000054 microg/L (year 2016). Risk of environmental impact of travoprost cannot be excluded, since no
ecotoxicity data are available.

Author: Health and Medical Care Administration, Region Stockholm