Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Ciprofloxacin

Information

This summary information comes from Fass. The risk is also confirmed by the assessment from Goodpoint.

Persistence. Ciprofloxacin is potentially persistent.
Bioaccumulation. Ciprofloxacin has low potential for bioaccumulationn.
Toxicity. Ciprofloxacin has a very high chronic toxicity.
Risk. The use of ciprofloxacin (sales data Sweden 2019) has been judged to entail a risk high of environmental impact.

Detailed information

Comment on Fass environmental information

Ciprofloxacin 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 2012”. 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 for Ciloxan (ciprofloxacin) from Novartis (downloaded 2021-08-16)

Hazard

Persistence: "Not readily degradable (28 days; Measurement of biological oxygen demand according to the guidelines published by OECD) (Halling-Sørensen, 2000). Ciprofloxacin is not readily biodegradable. Therefore, the phrase 'Ciprofloxacin is potentially persistent' is chosen."

Bioaccumulation: "Log Kow = 1.24 (estimated with ACD Log P software (Advanced Chemical Development, Toronto, Canada (Halling-Sørensen, 2000)."

Acute toxicity: There are data for 3 trophic levels, most sensitive cyanobacteria Mycrocystis aeruginosa EC50 = 5 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2019. PEC/PNEC = 86 which gives the risk high.

Fass environmental information for Ciproxin (ciprofloxacin) from Bayer (downloaded 2021-08-16)

Hazard

Persistence: "Biotic degradation. In a study on ready biodegradation according to OECD TG 301F ciprofloxacin was not degraded as 0 % biodegradation was observed at day 28. Abiotic degradation. Hydrolysis: In a study according to OECD TG 111 ciprofloxacin was hydrolytically stable at pH 4, 7, and 9 and at 50 °C. As no biotic or abiotic degradability of ciprofloxacin was observed the following phrase applies: “Ciprofloxacin is potentially persistent."

Bioaccumulation: "Log K of 1.1 at pH 2.5 (< 1 at pH 5.5-7) for ciprofloxacin (OECD TG 121)." 

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (Pimephales promelas) NOEC 29 d (development, survival and length) = 0.89 µg/L (OECD TG 210).

Risk

PEC/PNEC is based on sales data in Sweden in year 2019. PEC/PNEC = 4.22 which gives the risk moderate.

EU water legislation

Due to the risk of ecotoxicity of ciprofloxacin in water, the substance is monitored within the framework of EU water legislation to "improve knowledge of the occurrence and spread of antimicrobials in the environment".

The Swedish Agency for Marine and Water Management

Ciprofloxacin is among special pollutants in the Swedish Agency for Marine and Water Management regulation HVMFS 2019:25.

Report Goodpoint 2016 and pharmaceuticals residues in the aquatic environment

Measurements have shown that ciprofloxacin is present in the Swedish wastewater treatment plants at levels posing risk of selection of resistant bacteria.

The substance is included in Region Stockholm's table of pharmaceuticals with risk for negative environmental impact according to the environmental programme 2017–2021. Ciprofloxacin has been detected in treated wastewater in Region Stockholm.

Studies have shown that even low concentrations of antibiotics in the environment may trigger antibiotic resistance and therefore measures should be taken to ensure that as little as possible ends up in our environment.

The Wise list

Ciprofloxacin is recommended in the Wise list. Environmental classification of pharmaceuticals is taken into consideration, sometimes with other environmental aspects, when selecting pharmaceuticals for the Wise list. When comparable pharmaceuticals are equivalent to medical effects, safety and pharmaceutical efficacy, environmental impact and price are considered.

Suggestions on how to reduce emissions of ciprofloxacin

Concrete proposals on how to work to reduce emissions of environmentally harmful pharmaceuticals on the list have been developed in close cooperation with the Stockholm Drug and Therapeutics Committee's expert groups. The action proposals were developed from an environmental perspective. The patient's best always goes first and several pharmaceuticals on the list are also included in the Wise list. However, for such pharmaceuticals, there may be measures that could reduce the environmental impact.

Concrete proposal for ciprofloxacin

  • Ciprofloxacin is recommended for febrile UTI in adults in the Wise list as alternative first-hand treatment with trimethoprim sulfamethoxazole.
  • Ciprofloxacin should not be used in empirical treatment of lower urinary tract infection without fever, then nitrofurantoin is recommended (in the Wise List and is better from an environmental point of view than ciprofloxacin) or pivmecillinam (in the Wise Listan and is a reasonable alternative to ciprofloxacin from an environmental point of view). Nitrofurantoin is considered to be the lowest environmental risk of these.
  • For antibiotics, the general rule is as restrictive use as possible without risking the patient's health. Relevant cultivation is important in order to choose antibiotics that have a good effect with as narrow spectrum as possible.

References

  1. Fass.se för vårdpersonal.
  2. Europeiska unionens officiella tidning. Kommissionens genomförandebeslut (EU) 2020/1161 av den 4 augusti 2020.
  3. Goodpoint. Prioritering av läkemedel med miljörisk inom SLL. Stockholm: Goodpoint; 2016. Rapport LS 2016–0634.
  4. Provtagningar av läkemedelsrester i vatten, sediment och fisk för Region Stockholm.
  5. Halling-Sørensen B, Lützhøft HC, Andersen HR, Ingerslev F. Environmental risk assessment of antibiotics: comparison of mecillinam, trimethoprim and ciprofloxacin. J Antimicrob Chemother. 2000;46 Suppl 1:53-8; discussion 63-5.
  6. IVL Swedish Environmental Research Institute Ltd. Fick J, Lindberg RH, Kaj L, Brorström-Lundén E. Results from the Swedish National Screening Programme 2010. Subreport 3. Pharmaceuticals.
  7. IVL Swedish Environmental Research Institute Ltd Fick J, Lindberg RH, Fång J, Magnér J, Kaj L, Brorström-Lundén E. Screening 2014. Analysis of pharmaceuticals and hormones in samples from WWTPs and receiving waters. Rapport C 135.
  8. Bengtsson-Palme J, Larsson DG. Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation. Environ Int. 2016;86:140-9.
  9. Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 2011;7:e1002158.
  10. Havs- och vattenmyndighetens föreskrift HVMFS 2019:25.
  11. Region Stockholm. Förteckning över miljöbelastande läkemedel med åtgärdsförslag framtagen inom ramen för Region Stockholms miljöprogram 2017–2021.
  12. Stockholm Drug and Therapeutics committee. Kloka listan (Wise list).
  13. Stockholm Drug and Therapeutics committee. The Wise list 2015.

Author: Health and Medical Care Administration, Region Stockholm