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Simvastatin

Hazard 3 P 0 B 0 T 3 Risk See below

Information

The T-value in the score for hazard refers to chronic toxicity. Underlying data for P, B and T are from Fass (previously published environmental information for Zocord downloaded 2019-04-23) and refers to simvastatin hydroxy acid.

Summary of Product Characteristics (SPC)

Summary of Product Characteristics for Zocord (simvastatin), date of review of the SPC 2018-05-07. The main metabolites of simvastatin in human plasma are beta-hydroxy acid and four additional active metabolites. Following an oral dose of radioactive simvastatin in humans, 13% of the radioactivity is excreted in the urine and 60% in the faeces within 96 hours. The amount found in faeces consists of absorbed substance and metabolites excreted in bile and unabsorbed drug.

Fass environmental information

Fass environmental information for Zocord from MSD (downloaded 2019-04-23).

Hazard

Persistence: "Simulation Studies (OECD 308) (XIII): DT50 in water: 5-5.8 days; DT50 in sediment: 19.2-25 days; DT50 in total system: 5.6–7.8 days. [...] Because the OECD 308 study demonstrated a DT50 ≤ 32d for the total system, the summary phrase “Simvastatin is degraded in the environment” was selected."

Bioaccumulation: Log Kow = 2 (OECD 107). "Since log Kow < 4 the substance has low potential for bioaccumulation."

Toxicity: There are data for 3 trophic levels, most sensitive crustacean NOEC 21-dagar (reproduction) = 2 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2013. PEC/PNEC = 0.5 which gives the risk low.

Fass environmental information

Fass environmental information for Simvastatin Teva produced by Actavis (downloaded 2019-10-30).

Hazard

Persistence: No data.

Bioaccumulation: No data.

Toxicity: No data.

Risk

The risk of environmental effects of simvastatin cannot be excluded when ecotoxicological data are missing.

Manufacturer has on fass.se stated that that data about the environmental impact is missing for the substance so that the environmental risk cannot be calculated. It is voluntary for manufacturers to provide information on the environmental impact on fass.se.

Pharmaceutial residues in the aquatic environment

Report Pharmaceutial residues in the Stockholm aquatic environment. Simvastatin has been detected in the effluent from wastewater treatment plants at concentrations <5 <250 ng/L.

Report Goodpoint 2016

According to the report, if possible, simvastatin hydroxy acid and other active metabolites should be measured in wastewater.

Report Goodpoint 2019

Comparative assessment of environmental risk when using simvastatin, atorvastatin, rosuvastatin, pravastatin and ezetimibe from a Swedish perspective.

Although there are knowledge gaps in particular regarding relevant toxicity studies, there is no obvious environmental risk with any of the investigated substances in Swedish water given the current state of knowledge. No exchanges are therefore recommended from an environmental point of view. The risk seems entirely insignificant for the highly water-soluble substance rosuvastatin. More fat-soluble statins (simvastatin, atorvastatin) may be quite potent and (together with ezetimibe) represent a slightly higher risk than the others, but the levels in the environment are probably well below the concentrations that give rise to effects. However, more impact studies are needed. For ezetimibe and pravastatin, efficacy data are even more deficient. For pravastatin, however, the risk was assessed based on its relatively low fat solubility (and thus the ability to accumulate in biota) in relation to its potency in humans. Ezetimibe is more fat-soluble, but at least partially separated in the wastewater treatment plants, how much is unclear due to high detection limits. Based on measured bioconcentration potential, there is some, but low risk for this substance.

Author: Health and Medical Care Administration, Region Stockholm