Isavuconazole

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.

Assessment report Cresemba 2015

Assessment report for Cresemba (isavuconazole), Basilea Medical Ltd, 23 July 2015, EMA/596950/2015.

Hazard

Persistence: In an OECD 308 study on aerobic and anaerobic transformation in aquatic sediment systems, the DT₅₀ values in water were 3.3 and 4.4 days. In sediment, the DT₅₀ values were 222 and 32.8 days, while DT₅₀ values for the whole system were 204 and 32.8 days. The values refer to 20°C. Significant partitioning to sediment was observed. In one system, 70% of the substance had transferred to sediment within 7 days and remained stable until day 60, after which it decreased slightly to 57% after 100 days. In the other system, 47% of the substance had transferred to sediment after 7 days and subsequently decreased to 9% by the end of the study.

Bioaccumulation: The bioaccumulation potential was evaluated according to OECD 107. Log K_ow values were 3.84 at pH 7.2, 3.89 at pH 7.6–7.7, and 3.86 at pH 6.8–6.9.

Chronic toxicity: There are data for 2 trophic levels, most sensitive crustaceans (Daphnia sp.), NOEC 100 microg/L.

Risk

CHMP concluded that it could not be determined whether isavuconazole is a PBT or vPvB substance. Based on the available data, isavuconazole was not expected to pose a risk to groundwater or sewage treatment plants; however, a risk to surface waters and sediment could not be excluded. Therefore, the environmental risk assessment (ERA) was considered incomplete.

The applicant committed to conducting an algal toxicity study (OECD 201) and a sediment toxicity study (OECD 218) post-authorisation and to updating the ERA accordingly. In addition, CHMP required the updated assessment to use a more conservative exposure estimate based on the total residue approach (DOSEai 384.8 mg/inhabitant/day). The revised ERA and the results of the additional studies were to be submitted by the end of August 2016. No such follow-up data have been identified through searches of the EMA website (2026-08-20).

Assessment report Cresemba 2024

Assessment report for Cresemba, Basilea Pharmaceutica Deutschland GmbH, type II variation for an extension of indication, 27 June 2024, EMA/330882/2024.

Hazard

Persistence: No data.

Bioaccumulation: No data.

Toxicity: No data.

Isavuconazole was considered not to be a PBT or vPvB substance.

Risk

In the updated environmental risk assessment (ERA), the exposure assessment was refined using prevalence data and more realistic treatment durations compared with the worst-case assumptions applied in the original ERA. However, based on the intended use of Cresemba, a potential risk to the surface water compartment was identified. At the same time, the available data were considered insufficient to allow a definitive conclusion regarding the potential risk to sewage treatment plants (STPs), groundwater, and sediment. This is also reflected in the current Summary of Product Characteristics (SmPC), which states that Cresemba may pose a risk to the aquatic environment. No data are presented.

Fass environmental information

Fass environmental information for Cresemba from Unimedic Pharma (retrieved on 2026-08-20).

The environmental information published in Fass relates to isavuconazonium. According to the Summary of Product Characteristics (SmPC) for Cresemba, isavuconazonium sulfate is a water-soluble prodrug that is rapidly hydrolysed by plasma esterases to the active moiety, isavuconazole, following administration.

Hazard

Persistence: Isavuconazonium was not readily biodegradable. The DT₅₀ for aerobic degradation in a water-sediment system was 204 days, indicating that the substance is potentially persistent.

Bioaccumulation: "The log K_ow was determined to be 3.9 which is below the trigger value of 4. The substance has low potential for bioaccumulation."

Chronic toxicity: There are data for 3 trophic levels, most sensitive algae (Pseudokirchneriella subcapitata) EC₁₀ 20 microg/L.

Risk

PEC/PNEC is based on total sold amount API (active pharmaceutical ingredient) in Sweden year 2022.

PEC = 0.0009 microg/L.

Although toxicity data are available as described above, the company stated that "a risk of environmental impact from isavuconazonium cannot be excluded, as sufficient ecotoxicological data are not available."