Naloxone

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.

EMA’s scientific discussion Suboxone

EMA’s scientific discussion for naloxone from Suboxone (naloxone, buprenorphine), 19 October 2006.

The PEC calculation submitted by the applicant was incorrect and the predicted concentration exceeded 10 ng/L, requiring a Phase II environmental risk assessment. The text does not clearly specify whether this calculation refers to naloxone or buprenorphine.

Assessment report Suboxone 2020

Assessment report for naloxone from Suboxone for an extension to introduce a new pharmaceutical form, Indivior Europe Limited, 30 April 2020, EMA/302500/2020.

"The environmental risk assessment can stop in Phase I. Naloxone and buprenorphine hydrochloride PEC_surfacewater values are below the action limit of 0.01 µg/L and both active substances are not a PBT substance as log K_ow does not exceed 4.5. Therefore, naloxone and buprenorphine hydrochloride are not expected to pose a risk to the environment."

Assessment report Nyxoid

Assessment report for Nyxoid (naloxone), Mundipharma Corporation Limited, 14 September 2017, EMA/CHMP/690823/2017.

Hazard

Persistence: Naloxone is not readily biodegradable and partitions mainly to sediment. Degradation products in sediment are ≤ 10 %. Further testing is required, including a new adsorption/desorption study in three soil types and recalculation of sediment PEC. Potential terrestrial effects must be assessed, and the applicant has committed to provide these data post‑approval.

Bioaccumulation: According to OECD 107 (shake‑flask method), the substance has a log K_ow of 0.765 at pH 7, which is below the threshold of 4.5.

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 9900 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC = 0.02 microg/L.

PNEC = Lowest NOEC, 9900 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 990 microg/L

PEC/PNEC = 0.00002 which gives the risk insignificant.

Assessment report Zubsolv

Assessment report for naloxone from Zubsolv (naloxone, buprenorphine), Mundipharma Corporation Limited, 14 September 2017, EMA/659116/2017, (retrieved on 2026-01-26).

Hazard

Persistence: The substance is not readily biodegradable according to OECD 308, with less than 1% degradation observed after 100 days. In the study of aerobic and anaerobic transformation in aquatic sediment systems, DT₅₀ values of 4.8–10.3 days in water and 49.9–67.9 days for the whole system were reported. Between 55.5 and 81.7% of the substance shifted to the sediment after 100 days. Four metabolites were identified, none occurring at levels ≥ 10% at day 100.

Bioaccumulation: According to OECD 107 (shake‑flask method), the substance has a log K_ow of 0.765 at pH 7.

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 9900 microg/L. In one section of the assessment report, a value of 9.9 microg/L is stated, but this information is incorrect according to communication with EMA (email dated 20 January 2026).

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC = 0.022 microg/L.

PNEC = Lowest NOEC, 9900 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 990 microg/L.

PEC/PNEC = 0.00002 which gives the risk insignificant.

Comment on Fass environmental information

Naloxone has different classifications on fass.se. According to Lif (the trade association for the research-based pharmaceutical industry in Sweden) the various pharmaceutical companies compile environmental information for their active substances based on internal studies and published data. Based on data, which may thus differ between different pharmaceutical companies, the companies assess the environmental risk with guidance from “Environmental classification of pharmaceuticals at www.fass.se – Guidance for pharmaceutical companies 2025 v 1.0”. The Swedish Environmental Institute (IVL) reviews the assessment but does not have the task of coordinating/harmonizing environmental information from different pharmaceutical companies for the same active substance.

Fass environmental information Armoneve

Fass environmental information for naloxone from Armoneve (naloxone, oxycodone) from Mundipharma (retrieved 26 January 2027).

Excretion (metabolism)

No data are available on the excretion of naloxone after intranasal administration. Following intravenous administration of labelled naloxone, 38% of the dose was recovered in urine after 6 hours in healthy volunteers compared with 25% in opioid‑dependent patients. After 72 hours, 65% and 68% of the dose, respectively, had been excreted in urine.

Hazard

Persistence: In OECD 308 studies conducted in two water–sediment systems, DT₅₀ values of 49.9–67.9 days were observed for the total systems. A substantial proportion of the substance partitioned to the sediment, and the material balance remained 92–98.9% throughout the study. As the DT₅₀ is ≤ 120 days, naloxone is described as being slowly degraded in the environment.

Bioaccumulation: According to OECD 107 the substance has a log K_ow of 0.765 at pH 7.

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 9900 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2024.

PEC = 0.00824 microg/L.

PNEC = Lowest NOEC, 9900 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 990 microg/L.

PEC/PNEC = 0.000008 which gives the risk insignificant.

Fass environmental information Respinal

Fass environmental information for Respinal (naloxone) from DNE Pharma(retrieved on 2026-01-27).

Hazard

Persistence: In an OECD 301 F test, naloxone showed 0% degradation after 28 days and is therefore considered not readily biodegradable. Based on these findings, naloxone is regarded as potentially persistent.

Bioaccumulation: Log K_ow: 2.09 (method and pH not found).

Acute toxicity: There are data for 2 trophic levels, most sensitive algae EC₅₀ 51200 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022.

PEC = 0.0076 microg/L.

Risk of environmental impact of naloxone cannot be excluded since there is not sufficient data available to calculate a PEC/PNEC ratio.

Pharmaceuticals residues in the aquatic environment in Region Stockholm, Sweden

Naloxone has previously been analysed in Stockholm’s aquatic environment in Sweden, but is no longer included among the substances monitored.