Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Diclofenac

Hazard 4* P 3* B 0 T 1 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.se.

Diclofenac is not recommended in the Wise list (a list of recommended pharmaceuticals from the Stockholm Drug and Therapeutics Committee).

Fass environmental information

Fass environmental information for Voltaren (diclofenac) (downloaded 2018-06-21).

Hazard

Persistence: "While the results from Kunkel 2008 would even justify the statement "diclofenac is degraded in the environment", the fact that no standard OECD308 study is available has led to a more conservative assumption."

Bioaccumulation: "BCFss = 3-5 (OECD305, 1996, Harlan Laboratories Study D24068), 5 -11 (Brown et al. 2007), 2.5 - 29 (Fick et al. 2010)."

Chronic toxicity: There is NOEC for 3 trophic levels, lowest NOEC for fish (OECD210, Danio rerio, 34 days) 0.320 mg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2015. PEC/PNEC = 0.036 which gives the risk insignificant, i.e. consideration has not been given to measured levels in the environment.

Report Goodpoint 2018

Comparative assessment of environmental risk when using diclofenac, naproxen, ibuprofen, ketoprofen, etoricoxib, and paracetamol in Sweden (Report Goodpoint 2018). Log P for diclofenac from PubChem is reported to be 3.9–4.51. Available data clearly indicate that diclofenac represents the highest risk of the NSAID/analgesics investigated. The NSAIDs (ibuprofen, ketoprofen and naproxen) + paracetamol recommended in the Wise list are all better from an environmental point of view than diclofenac. Paracetamol is a very safe alternative from an environmental point of view. The others are also expected to cause a low environmental risk, somewhat elevated to ketoprofen.

Other information

The acute toxicity to aquatic organisms is assessed as high (T = 2). Due to the risk of ecotoxicity in water, diclofenac has previously been monitored within the framework of EU water legislation. There is now enough data to assess whether diclofenac is to be proposed as a priority substance when the European parliament and the Council next time proposes a revised directive regarding priority substances in the field of water policy. For Sweden, the Swedish Agency for Marine and Water Management has diclofenac among special pollutants in its regulation HVMFS 2013:19 (Updated 2017-01-01).

The degree of purification of diclofenac in the Swedish treatment plants is low, i.e. most of the substance comes out in our nature. In Sweden diclofenac is found in surface water at levels reported to have effects on fish.

Diclofenac is included in the Stockholm County Council's table of pharmaceuticals with risk for negative environmental impact according to the environmental program 2017–2021 based on lowest effect concentration, LOEC = 1 microg/L, and concentrations found in the environment. Diclofenac has been detected in treated wastewater and surface water in Stockholm County in the last five years (2012–2016).

In India and Pakistan several species of vultures are endangered because of the veterinary use of diclofenac when the dead cows for cultural reasons is left to the vultures. In recent years the same problem has been seen in eagles in same areas. Similar effects on vultures and eagles are also suspected in Africa and there is even some concern in Europe for example in parts of Spain, where carcasses are left in the open for wild animals to eat.

Diclofenac has been associated with a greater risk of serious cardiovascular events than other COX inhibitors in several studies.

Diclofenac can be purchased without a prescription in Sweden. Since 3 October 2018, all pharmacies will inform customers about diclofenac's negative impact on the environment.

Buying diclofenac without a prescription is questioned again (2018-10-04) for medical reasons and for environmental reasons.

Suggestions on how to reduce the release of diclofenac

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 advice. 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 diclofenac

  • Diclofenac is not recommended in the Wise list.
  • Note that diclofenac is also sold without prescription (tablets, gel, patches and spray). What are your recommendations for patients with regard to OTC pain relief pharmaceuticals?

References

  1. Fass.se för vårdpersonal
  2. Goodpoint. Prioritering av läkemedel med miljörisk inom SLL. Stockholm: Goodpoint; 2016. Rapport LS 2016–0634.
  3. Goodpoint. Jämförande bedömning av miljörisk vid användning av diklofenak, naproxen, ibuprofen, ketoprofen, etoricoxib samt paracetamol. Stockholm; Goodpoint; 2018.
  4. Havs- och vattenmyndigheten. Havs- och vattenmyndighetens föreskrifter om klassificering och miljökvalitetsnormer avseende ytvatten. HVMFS 2013:19.
  5. 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.
  6. Triebskorn R, Casper H, Scheil V, Schwaiger J. Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio). Anal Bioanal Chem. 2007;387:1405-16.
  7. Fick J, Lindberg RH, Parkkonen J, Arvidsson B, Tysklind M, Larsson DG. Therapeutic levels of levonorgestrel detected in blood plasma of fish: results from screening rainbow trout exposed to treated sewage effluents. Environ Sci Technol. 2010;44:2661-6.
  8. Fick J, Lindberg RH, Tysklind M, Larsson DG. Predicted critical environmental concentrations for 500 pharmaceuticals. Regul Toxicol Pharmacol. 2010;58:516-23.
  9. Näslund J, Fick J, Asker N, Ekman E, Larsson DGJ, Norrgren L. Diclofenac affects kidney histology in the three-spined stickleback (Gasterosteus aculeatus) at low μg/L concentrations. Aquat Toxicol. 2017;189:87-96.
  10. SLL. Sammanställning av läkemedelsprovtagningar - Bearbetning av regional försäljningsstatistik av läkemedel samt datamaterial från Stockholms läns landstings mätprogram för läkemedelssubstanser i vattenmiljö, 2012–2016.
  11. Helmfrid I, Eriksson Cajsa. Läkemedelsrester från sjukhus och avloppsreningsverk. Universitetssjukhuset, Landstinget i Östergötland. Rapport 2010:1
  12. Naturvårdsverket. Avloppsreningsverkens förmåga att ta hand om läkemedelsrester och andra farliga ämnen. Rapport 2008
  13. Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018;362:k3426.
  14. Sveriges Apoteksförening. Alla apotek börjar informera om diklofenaks miljöpåverkan. Pressmeddelande 2018-10-03.
  15. Helene Wallskär. Receptfrihet för diklofenak ifrågasätts. Läkemedelsvärlden 2018-10-04.
  16. Stockholms läns landsting. Förteckning över miljöbelastande läkemedel med åtgärdsförslag framtagen inom ramen för SLL:s miljöprogram 2017–2021.

Author: The Pharmaceutical unit of Region Stockholm