Fentanyl

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 can be found in the public investigation report (PAR/EPAR for medicinal product through a centralized procedure). Since the benefit/risk assessment for human medicinal products at present does not include environmental effects, an update of the environmental risk assessment is not required for renewals of marketing authorizations. There is thus no requirement for companies to stay informed about the development of their substances from an environmental point of view and consequently to update the environmental risk assessment as new data are published.

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, not all medicinal products containing the same active substance.

Assessment report on PecFent

Assessment report for PecFent (fentanyl), Procedure No. EMA/H/C/001164 from 2010-09-14.

"No experimental environmental risk assessment is required for fentanyl citrate because the predicted concentration in surface water is lower than the action limit, the log K_ow is lower than 4.5, and there is no indication that fentanyl might effect the environment at concentrations lower than 10 ng/l."

Assessment report on Effentora

Assessment report "EPAR - Scientific Discussion" for Effentora (fentanyl) 2008-04-23.

"A phase I environmental risk assessment has been performed. Because the log K_ow is below 4.5, screening for persistence, bioaccumulation and toxicity was not considered necessary. For the calculation of the Predicted Environmental Concentration (PEC) the default penetration factor (Fpen) of 0.01 has been refined to 0.001 based on published data on the target patient population (number of cancer patients suffering from breakthrough pain) and commercial experience. This was considered to be acceptable. Using these estimates, the calculated PEC value is well below the threshold for a phase II assessment of 0.01 μg/l. It is therefore concluded that Effentora is unlikely to represent a risk for the environment following the suggested usage in patients."

Comment: Fentanyl has only undergone a phase I study according to regulatory requirements for environmental risk assessments (European Medicines Agency, EMA: Committee for Medicinal Products for Human Use (CHMP). Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use. 1 June 2006.) A phase I study includes data on bioaccumulation and calculates the concentration of fentanyl in the environment (PEC_{Surface water}). If specified limit values ​​are not exceeded, the company does not need to conduct a phase II study that includes data on toxicity and persistence and calculation of risk based on PEC/PNEC.

Fass environmental information

Fass environmental information for Durogesic (downloaded 2024-04-26).

Hazard

Persistence: "Fentanyl is not readily biodegradable in a biodegradability test according to OECD No. 301 F: “Manometric respirometry test”. Within the given test period of 28 days and at the given test conditions fentanyl HCl cannot be regards as readily biodegradable. Consequently, the medicine is potentially persistent."

Bioaccumulation: "The partition coefficient octanol/water was to be log K_ow = 3.94 (pH = 3) using unknown internal method. The ChemSpider ACD/Percepta log K_ow for Fentanyl = 3.89. The substance therefore has low potential for bioaccumulation."

Toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia magna) EC₅₀ = 11 100 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in 2022. PEC/PNEC = 0.00008558846 which gives the risk insignificant.

Used patch

Note that a used patch still contains the active substance and should be returned to the pharmacy for disposal (in Sweden).