Assessing the ongoing threat from veterinary non-steroidal anti-inflammatory drugs to Critically Endangered Gyps vultures in India

Abstract

Use of the veterinary drug diclofenac is responsible for bringing three species of Gyps vultures endemic to South Asia to the brink of extinction, and the Government of India banned veterinary use of the drug in May 2006. To evaluate the effectiveness of the ban we undertook surveys of > 250 veterinary and general pharmacies in 11 Indian states from November 2007 to June 2010. Twelve different classes of non-steroidal anti-inflammatory drugs (NSAIDs) were purchased from 176 pharmacies. Other than meloxicam (of negligible toxicity to vultures at likely concentrations in their food), diclofenac and ketoprofen (both toxic to vultures), little is known of the safety or toxicity of the remaining nine NSAIDs on sale. Meloxicam was the most commonly encountered drug, sold in 70% of pharmacies, but 50% of the meloxicam brands sold had paracetamol (acetaminophen) as a second ingredient. Diclofenac and ketoprofen were recorded in 36 and 29% of pharmacies, respectively, with states in western and central India having the highest prevalence of diclofenac (44–45%). Although the large number of manufacturers and availability of meloxicam is encouraging, the wide range of untested NSAIDs and continued availability of diclofenac is a major source of concern. Circumvention of the 2006 diclofenac ban is being achieved by illegally selling forms of diclofenac manufactured for human use for veterinary purposes. To provide a safer environment for vultures in South Asia we recommend reducing the size of vials of diclofenac meant for human use, to increase the costs of illegal veterinary use, and taking action against pharmaceutical manufacturers and pharmacies flouting the diclofenac ban.

Avian scavengers and the threat from veterinary pharmaceuticals

“…Evidence for the potential toxicity of various NSAIDs to 79 species of birds suggests that compounds other than diclofenac, in particular carprofen and flunixin, may be associated with mortality with renal failure and/or gout in raptors [20]. However, to the best of our knowledge, carprofen is not used in India and flunixin is administered infrequently [26]. The only other NSAID thought to have a high potential to cause mortality in Gyps vultures in India is ketoprofen [33].…”

“…Hence, despite its perceived efficacy for treating livestock, its popularity and low cost [26], there were significant perceived drug safety drawbacks to the use of diclofenac as a veterinary NSAID. By contrast, veterinary professionals reported few side effects from meloxicam (table 1), though this might partly be because it had been in use for a short time.…”

“…However, there is also cause for concern in these results. The use of other NSAIDs is evident from analyses of liver samples from domesticated ungulates in India and from surveys of veterinary pharmacies [12,26], and we consider it likely that the difference between the increase in meloxicam and the reduction in diclofenac is due to the availability of these other compounds for veterinary use. Among these compounds are several with unknown toxicity to vultures and one (ketoprofen) which has been shown to be toxic to Gyps vultures at concentrations likely to be encountered by wild vultures feeding from the carcass of an ungulate given a standard veterinary dose of the drug [33].…”

“…Advocating the pharmacological and drug safety benefits of properly formulated versions of meloxicam to veterinarians and farmers in the Indian sub-continent may be beneficial for vulture conservation and animal welfare, and hasten the switch from diclofenac to 'vulture-safe' meloxicam [37]. Although veterinary formulation, sale and veterinary use of diclofenac has been illegal across much of the Indian subcontinent since bans were issued in mid-2006, large volume injectable human formulations remain widely available in the loosely regulated pharmaceutical marketplace in India [26]. The analysis presented here, and in previous work [11,12,17,18,24,30], regarding the level of diclofenac contamination in livestock carcasses sampled in India demonstrates that illegal diclofenac use on domesticated ungulates continued after the ban at least up to 2010, though it had declined significantly.…”

“…Given that the toxicity of diclofenac to Gyps was reported in 2004 [13], this rapid positive action to halt the decline of Asia's vultures was commendable. However, diclofenac remains a serious threat to vultures in the Indian sub-continent because enforcement of the regulations has been incomplete [24,25] and formulations for humans, in vials that contain a larger quantity of the drug than a human dose, are on sale widely and misused to treat ungulates [26].…”