The plastic straw of pain relief: The deleterious effects of diclofenac on the environment

Physicians, including physiatrists, are often tasked with treating acute and chronic pain. Physicians often prescribe a multimodal approach to managing pain including teaching self-management skills, physical therapy, medications, and injections. Multiple classes of medications can be considered including non-steroidal anti-inflammatories (NSAIDs), neuropathic agents, antispasmodics and opioids. Given the morbidity and mortality of opioids, there has been a push to use nonopioid analgesia.1 The use of NSAIDs, including diclofenac, is very common especially given over-the-counter formulations with an estimated 30 billion NSAID doses consumed annually in the United States and 877 tons of diclofenac sold in 2007.2, 3 Physicians consider indications, side effects, and drug–drug interactions of the medications they are prescribing; however, they are not trained to consider the environmental impacts of the medications they prescribe. Diclofenac is the most frequently found NSAID in the environment followed by naproxen and ibuprofen.4 Here we describe the environmental impacts of diclofenac and present solutions and next steps for physicians treating painful conditions. Diclofenac can enter surface water through wastewater or agricultural runoff.5 Wastewater is filtered through water treatment plants then routed to surface water. Wastewater treatment plants have a limited capacity to remove NSAIDs, which contributes to contamination of surface water.3 Removal efficiencies of diclofenac in wastewater treatment plans range from 0% to 80% with the majority of plants in the 21%–40% removal rate range.3 The large differences seen in removal efficiency may be due to specific treatment guidelines at various plants with differences in anoxic–oxic ratios and acidic conditions. These differences affect the degradation and absorption of diclofenac into removal sludge in the treatment plants.3 Ineffective removal of diclofenac by treatment plants results in persistent concentrations of the drug in surface and ground water. Diclofenac can accumulate in fish, algae, and invertebrates at concentrations found in the environment.6 It has been shown to cause damage to inner organs of trout and was thought to be the main factor in the near total extinction of vultures in Pakistan, Nepal, and India between 1998 and 2003.7, 8 In one study, 85% of the vulture deaths were attributed to visceral gout secondary to renal failure from a toxic cause.7 The only identifiable toxin was diclofenac and 100% of the vultures that died from acute renal failure had detectable levels of diclofenac in their kidneys. The consumption of livestock treated with diclofenac was the most likely source as the low concentrations in water sources would be unlikely to cause toxicity. Dead livestock is a common food source for vultures and a potential explanation for why they may be effected more than other animals.7 In 2006, the veterinary use of diclofenac was banned in those countries and since that time there has been a decrease in the rate of decline of vultures in Nepal and India.9 It is unclear if veterinary diclofenac use is more common in these Asian countries than other countries.10 Notably, Spain has also seen diclofenac toxicity in vultures and there has been a call to ban diclofenac in Europe given similar concerns.10 Vultures are important to the ecosystem as they eliminate carcasses that contain disease and reduce food supplies for feral dogs.9 Both acute toxicity leading to mortality and chronic toxicity to diclofenac have been described in fresh water invertebrates in lab based experiments.11 However, the acute toxicity occurred at concentrations much higher than found in the environment. The chronic toxicity did occur at concentrations consistent with surface water samples.3 Fresh water invertebrates play an important role in the ecosystem by recycling nutrients and transferring energy along the food chain.11 Other NSAIDs such as naproxen and ibuprofen have also been implicated in ecotoxicity. Similar to diclofenac, acute toxicity in water fleas and shrimp was found at concentrations much higher than environmental levels with chronic toxicity to these products more consistent with environmental concentrations.5 When comparing the effects of naproxen and diclofenac on fish using similar lab-based exposure study designs, Näslund et al. found similar types of adverse events in both groups but observed those effects in the naproxen group only at concentrations much higher than environmental concentrations.12 Interestingly, studies examining the pharmacokinetic and pharmacodynamics of meloxicam in vultures have shown that it is unlikely to accumulate in vultures due to a short half-life of elimination and rapid metabolism of the drug.13 Investigation of meloxicam in vultures occurred because of the need for a safe veterinary analgesic after the ban of diclofenac in 2006 in Asian countries. Diclofenac is the most frequently detected NSAID in environmental samples and has been detected at concentrations as high as 19 μg/L and reported in the aquatic environment in 50 countries.4, 11 Additionally the topical application of diclofenac results in higher concentrations of the drug in the aquatic environment due to lower absorption rates.14 Diclofenac has not only been found in surface water but in the inner organs of animals in these environments.6, 8 Given the environmental impacts of NSAIDs, and in particular diclofenac, it is imperative that clinicians are aware of these issues, counsel their patients about the environmental impacts of these medications, and consider alternative treatments. Tools to evaluate the environmental impact of pharmaceuticals have been developed and we encourage clinicians to use these prior to prescribing medications.15 An English version of this tool is available at https://janusinfo.se/beslutsstod/lakemedelochmiljo/pharmaceuticalsandenvironment.4.7b57ecc216251fae47487d9a.html. As previously mentioned, naproxen has been shown to be a better alternative than diclofenac and is more effectively removed in wastewater treatment plants than diclofenac.12, 16 Finally, if clinicians are prescribing diclofenac gel they should counsel their patients to wipe their hands with a paper towel after application of the gel and before washing their hands as this has been shown to decrease the concentration of diclofenac in waste water with minimal effects of solid waste on surrounding surface water.17 Patients should also wipe off the location of application of the gel before showering. Topical ketoprofen has similar efficacy as topical diclofenac and may be an alternative topical medication option.18 Further clinician education on the environmental impacts of pharmaceuticals is needed, with incorporation of this education into medical education, especially for providers involved in pain management. Future studies should include the development of medications that are safer for the environment and studies examining practice pattern changes after education about the environmental effects of prescription medications. Additionally, further research is needed focused on weighing the benefits of medications compared to their side effects and environmental impacts along with strategies to educate our patients and help them make informed choices. The authors would like to thank our patient who originally brought this information to our attention. Without her advocacy, we would not have been aware of such an important topic. Dr Brakke Holman serves as a member of the board of American Academy of Physical Medicine and Rehabilitation.