Second vulture-safe veterinary painkiller identified! Tolfenamic Acid

In 2003, the veterinary use of diclofenac to treat cattle was discovered to be the cause of catastrophic vulture declines across South Asia. There was an urgent need to identify alternative, safe NSAIDs for veterinary use. The NSAID meloxicam was tested in 2006 and found to be both safe to vultures and effective in treating cattle. Unfortunately, various other NSAIDs have also been tested since then and so far all have been shown to be toxic to vultures. Therefore, it is hugely significant that a systematic safety testing study led by the Indian Veterinary Research Institute (IVRI) with the Bombay Natural History Society (BNHS) and the Royal Society for the Protection of Birds (RSPB) has identified tolfenamic acid as the second confirmed vulture-safe NSAID after meloxicam.

A total of 38 wild-caught Himalayan Griffon Vultures, along with single captive White-rumped and Long-billed Vultures from the conservation breeding population, were given doses of tolfenamic acid by oral gavage at the maximum possible level likely to be encountered by birds feeding on carcasses in the wild. This was calculated based on concentrations of diclofenac found in cattle carcasses in India, which showed that vets and livestock owners routinely give doses of this drug much higher than the recommended level. In addition, four Himalayan Griffons were also fed buffalo meat from animals given double the recommended dose of tolfenamic acid just prior to death. Although two of the Himalayan Griffons given the extremely high dose by gavage died, all other birds survived without an increase in uric acid levels in the blood, which is the usual sign of kidney failure caused by NSAID poisoning. These findings show that tolfenamic acid is safe to wild vultures at levels of the drug that they are likely to be exposed to.

IVRI and BNHS giving a vulture an oral dose. Chris Bowden, RSPB.

Dr Chandra Mohan, Scientist of IVRI and the lead investigator of the study said “Every painkiller available has slightly different properties, and the vets often complained of not having a second choice of NSAIDs. But we are very pleased to report that tolfenamic acid been found as a second safe NSAID drug.”

Dr Vibhu Prakash, Principal scientist and vulture programme Director of BNHS explained “by testing first on the less threatened Himalayan Griffon Vultures, we could establish the comparative safety of the drug. We then also tested it on the most threatened species held at the breeding centre at Pinjore, Haryana.”

The results of this study are reported in an IVRI report, while a pre-print publication, entitled “Experimental safety testing shows that the NSAID tolfenamic acid is not toxic to Gyps vultures in India at concentrations likely to be encountered in cattle carcasses” is freely available.

Dr A M Pawde, Incharge & Dr M. Karikalan, Scientist Centre for Wildlife, IVRI said “IVRI is particularly pleased to help identify this safe alternative for veterinarians, and it is important that this information is made available quickly, to avoid use of other more toxic alternatives (for the vultures) becoming popular in veterinary use.”  They added “Tolfenamic acid does have certain properties which make it slightly more similar to diclofenac in its ability to reduce fever as well as inflammation, and this may be important in being taken up more widely by vets across the country.”

Dr. Triveni Dutt, the Director of ICAR-Indian Veterinary Research Institute commented “this is good news for vulture conservation and can help decision-makers to take important steps towards banning the NSAIDs which are proven to be toxic, such as aceclofenac and ketoprofen.”

Tolfenamic acid is already licensed and produced by a number of different Indian manufacturers, being out of patent, and similarly priced to other drugs.

Professor Rhys Green of Cambridge University UK, and Chair of the SAVE consortium said “After sixteen years and considerable effort in safety testing NSAIDs on vultures we have found a second vulture-safe NSAID for use on cattle. This is important and welcome news. It will reduce the pressure to use toxic alternatives such as aceclofenac, ketoprofen, flunixin and nimesulide, which are still available and legally used in the region. Veterinary use of all of these toxic drugs should be banned immediately.”

He added “So this is highly significant, and good news for vulture conservation, but only if it helps decision-makers to take more urgently needed action to remove licenses for similar drugs that are proven to be toxic, such as aceclofenac and ketoprofen. Neighbouring Bangladesh has earlier this year taken this important and commendable step to extend local ketoprofen bans to national bans, and if India can do this for aceclofenac and ketoprofen, this will be real progress.”

Please contact chris.bowden@rspb.org.uk for further information or contacts.

16 Comments

  1. D SWARUP on 9th September 2021 at 1:23 pm

    Very good information and remarkable achievement by IVRI and BNHS team. Congratulations. Keep it up teammates

    • Beena on 12th September 2021 at 3:45 am

      Highly informative research and useful for all veterinarians. Congratulations and good luck for the entire team..

    • Chris Bowden on 12th September 2021 at 5:59 am

      Thank you Dr Swarup. And greatly appreciate your help in passing this story to relevant outlets – eg
      https://indiancattle.com/veterinary_safe_painkiller_tolfenamic_acid/

      I hope others can help in such ways to disseminate this news, Chris Bowden

  2. Juergen Daemmgen on 9th September 2021 at 2:03 pm

    Jürgen Dämmgen, Germany,
    this is really good news after many years of hard work and frustration. Congratulations to a great team and good luck for the vultures of the world!

    • Chris Bowden on 12th September 2021 at 6:01 am

      Many thanks! And thank you for your ongoing support to this cause!

  3. Bhupal Nepali on 9th September 2021 at 3:59 pm

    Very glad news .

  4. Richard Cuthbert on 10th September 2021 at 9:08 am

    Very good news to see this joint research and development and another safe drug to support vulture conservation. Congratulations to all involved.

  5. Nishand Venugopal on 10th September 2021 at 9:09 am

    Interesting News, Best wishes for the work.
    Recently I wrote this poem, hope the message to protect vultures will reach wider audiences. https://sciencenextdoorcom.wordpress.com/2021/09/02/vultures-natures-winged-avengers/

    • Chris Bowden on 12th September 2021 at 6:16 am

      Many thanks Nishand, and indeed for your willingness to incorporate feedback. We will be pleased to post this on our SAVE Facebook page, and I hope you can reach other audiences with these messages and further awareness.

  6. Colonel.Dr.Navaz on 10th September 2021 at 3:50 pm

    Great news.We the Veterinarians at People for Animals Wildlife hospital and conservation center in Bangalore,extensively use Meloxicam and have found no toxic effects.

    • Chris Bowden on 12th September 2021 at 6:23 am

      Dear Col Dr Navaz, Manythanks for this feedback, and indeed my understanding is that many vets (including in Europe) are already perfectly happy with using meloxicam, which we have known to be safe for vultures since 2005. Having one more option (tolfenamic acid) available to vets (with more anti-pyretic properties, so perhaps more similar to diclofenac in that way) is something that some vets have been asking for. But if meloxicam already covers the needs for you, then this is ideal and no need to change. Further feedback on this point will be welcome.

      • Dr. Dinesh Kumar, HD P&T, IVRI on 12th September 2021 at 6:40 am

        Very inspiring/refreshing news after devastation of vulture population. The coordinated approach is most appreciated. Meloxicam and tolfenamic acid have giver good results, pharmacovigilence should continue.
        Thanking you

        • Chris Bowden on 13th September 2021 at 12:03 pm

          With thanks for your support and IVRI’s role in this work. Fully agreed that extending the pharmacovigilence on this and all NSAIDs in veterinary use is definitey both extremely important and urgent. Warm regards.

  7. Susan Sharma on 11th September 2021 at 8:26 am

    excellent news

  8. Dr. P. S. Banerjee on 12th September 2021 at 6:05 am

    Congrats Team IVRI. Proud of you.

  9. Jim Wellehan on 22nd September 2021 at 7:31 pm

    I’m pretty stunned that a 5% (2/38) mortality rate is considered safe.

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