Flunixin

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Flunixin
Flunixin Structural Formulae V.1.svg
Clinical data
AHFS/Drugs.com International Drug Names
ATCvet code
Identifiers
  • 2-[[2-Methyl-3-(trifluoromethyl)phenyl]amino]pyridine-3-carboxylic acid
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.115.991 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C14H11F3N2O2
Molar mass 296.249 g·mol−1
3D model (JSmol)
  • CC1=C(C=CC=C1NC2=C(C=CC=N2)C(=O)O)C(F)(F)F
  • InChI=1S/C14H11F3N2O2/c1-8-10(14(15,16)17)5-2-6-11(8)19-12-9(13(20)21)4-3-7-18-12/h2-7H,1H3,(H,18,19)(H,20,21) X mark.svgN
  • Key:NOOCSNJCXJYGPE-UHFFFAOYSA-N X mark.svgN
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Flunixin is a nonsteroidal anti-inflammatory drug (NSAID), analgesic, and antipyretic used in horses, cattle and pigs. It is often formulated as the meglumine salt. In the United States, it is regulated by the U.S. Food and Drug Administration (FDA), and may only be lawfully distributed by order of a licensed veterinarian. There are many trade names for the product.

Contents

Dosage and uses in horses

Flunixin is administered at a dose of 1.1 mg/kg. [1] The full analgesic and antipyretic effects usually occur 1–2 hours following treatment, but there is often an effective analgesic effect within approximately 15 minutes. Despite its short plasma half life of 1.6–2.5 hours, effects can persist for up to 30 hours, [2] with maximal effects occurring between 2 and 16 hours. This is likely due to accumulation of the drug at inflammatory foci. Flunixin is primarily eliminated by the kidneys. [3]

Because it targets the inflamed tissue, flunixin is mainly used for colic pain, musculoskeletal pain, and ocular pain. [4] [5] [6] It is also used as an antipyretic and to reduce the effects of endotoxemia. [7]

Side effects and precautions

Flunixin is labeled for no more than 5 days of consecutive use and prolonged use increases the risk of toxicity. In horses, this includes gastric ulcers, [8] right dorsal colitis, [9] and nephrotoxicity. [10]

Flunixin is a prohibited substance under International Federation for Equestrian Sports rules, [11] and its use is prohibited or restricted by many other equestrian organizations. At labeled dose (1.1 mg/kg) given IV, detection time was found to be 144 hours. [12] However, drug recycling from bedding contamination by treated horses has been shown to potentially increase the clearance time. [13]

Administration

Flunixin may be given orally as a paste or as granules in feed. It can also be used intramuscularly (IM) or intravenously (IV). However, it is very irritating to tissue and IM administration has been associated with myonecrosis in horses, [14] so IV administration is preferred.

Administration of phenylbutazone to a horse also receiving flunixin has been shown to increase the risk of toxicity without improving analgesia. [15] [16] For this reason, concurrent administration with another NSAID is not recommended. Doubling the dose of flunixin produces no improvement in analgesia, while potentially increasing the risk of toxicity. [4]

In the US, the only labeled route for flunixin administration in cattle is intravenous and pour-on. This is not the case in other countries; for example, in the UK, Allevenix is licensed for IV and intramuscular use, [17] and a pour-on product also exists. [18]

In the US flunixin is not labelled for goat use, however, flunixin may be used in goats in an extra-label fashion under appropriate veterinary guidance. Flunixin administered subcutaneously to dairy goats may carry a milk withdraw recommendation of 36-60 hours. [19] Interestingly, when given subcutaneously to goats in that study, tissue injury, such as seen in horses with intramuscular administration, was not observed.

See also

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References

  1. ↑ McIlwraith CW, Frisbie DD, Kawcak CE (2001). "Nonsteroidal Anti-Inflammatory Drugs". Proc. AAEP. 47: 182–187.
  2. ↑ May SA, Lees P (1996). "Nonsteroidal anti-inflammatory drugs". In McIlwraith CW, Trotter GW (eds.). Joint Disease in the Horse. Philadelphia: WB Saunders. pp. 223–237.
  3. ↑ Soma LR, Behrend E, Rudy J, Sweeney RW (November 1988). "Disposition and excretion of flunixin meglumine in horses". American Journal of Veterinary Research. 49 (11): 1894–8. PMID   3247913.
  4. 1 2 Foreman JH, Bergstrom BE, Golden KS, Roark JJ, Coren DS, Foreman CR, Schumacher SA (December 2012). "Dose titration of the clinical efficacy of intravenously administered flunixin meglumine in a reversible model of equine foot lameness". Equine Veterinary Journal. Supplement. 44 (43): 17–20. doi: 10.1111/j.2042-3306.2012.00655.x . PMID   23447872.
  5. ↑ Jochle W, Moore JN, Brown J, Baker GJ, Lowe JE, Fubini S, Reeves MJ, Watkins JP, White NA (June 1989). "Comparison of detomidine, butorphanol, flunixin meglumine and xylazine in clinical cases of equine colic". Equine Veterinary Journal. Supplement. 21 (7): 111–6. doi:10.1111/j.2042-3306.1989.tb05668.x. PMID   9118091.
  6. ↑ Hilton HG, Magdesian KG, Groth AD, Knych H, Stanley SD, Hollingsworth SR (2011). "Distribution of flunixin meglumine and firocoxib into aqueous humor of horses". Journal of Veterinary Internal Medicine. 25 (5): 1127–33. doi: 10.1111/j.1939-1676.2011.0763.x . PMID   21781166.
  7. ↑ Bryant CE, Farnfield BA, Janicke HJ (February 2003). "Evaluation of the ability of carprofen and flunixin meglumine to inhibit activation of nuclear factor kappa B". American Journal of Veterinary Research. 64 (2): 211–5. doi: 10.2460/ajvr.2003.64.211 . PMID   12602591.
  8. ↑ Videla R, Andrews FM (August 2009). "New perspectives in equine gastric ulcer syndrome". The Veterinary Clinics of North America. Equine Practice. 25 (2): 283–301. doi:10.1016/j.cveq.2009.04.013. PMID   19580940.
  9. ↑ McConnico RS, Morgan TW, Williams CC, Hubert JD, Moore RM (November 2008). "Pathophysiologic effects of phenylbutazone on the right dorsal colon in horses". American Journal of Veterinary Research. 69 (11): 1496–505. doi: 10.2460/ajvr.69.11.1496 . PMID   18980433.
  10. ↑ Black HE (1986). "Renal toxicity of non-steroidal anti-inflammatory drugs". Toxicologic Pathology. 14 (1): 83–90. doi:10.1177/019262338601400110. PMID   3487106. S2CID   28865193.
  11. ↑ "FEI Prohibited Substances List". 28 October 2013. Retrieved 23 January 2016.
  12. ↑ "FEI List of Detection Times" (PDF). Retrieved 23 January 2016.
  13. ↑ Popot MA, Garcia P, Bonnaire Y (December 2011). "Doping control in horses: housing conditions and oral recycling of flunixin by ingestion of contaminated straw". Journal of Veterinary Pharmacology and Therapeutics. 34 (6): 612–4. doi:10.1111/j.1365-2885.2011.01276.x. PMID   21995754.
  14. ↑ Peek SF, Semrad SD, Perkins GA (January 2003). "Clostridial myonecrosis in horses (37 cases 1985-2000)". Equine Veterinary Journal. 35 (1): 86–92. doi:10.2746/042516403775467513. PMID   12553469.
  15. ↑ Foreman JH, Ruemmler R (November 2011). "Phenylbutazone and flunixin meglumine used singly or in combination in experimental lameness in horses". Equine Veterinary Journal. Supplement. 43 (40): 12–7. doi: 10.1111/j.2042-3306.2011.00485.x . PMID   22082440.
  16. ↑ Reed SK, Messer NT, Tessman RK, Keegan KG (March 2006). "Effects of phenylbutazone alone or in combination with flunixin meglumine on blood protein concentrations in horses". American Journal of Veterinary Research. 67 (3): 398–402. doi:10.2460/ajvr.67.3.398. PMID   16506899.
  17. ↑ "Allevinix 50 mg/ml solution for injection for cattle, pigs and horses". NOAH Compendium. National Office of National Health. Retrieved 19 April 2017.
  18. ↑ "Finadyne Transdermal 50 mg/ml pour-on solution for cattle". NOAH Compendium. National Office of National Health. Retrieved 19 April 2017.
  19. ↑ Smith JS, Marmulak TL, Angelos JA, Lin Z, Rowe JD, Carlson JL, Shelver WL, Lee EA, Tell LA (2020). "Pharmacokinetic Parameters and Estimated Milk Withdrawal Intervals for Domestic Goats (Capra Aegagrus Hircus) After Administration of Single and Multiple Intravenous and Subcutaneous Doses of Flunixin Meglumine". Frontiers in Veterinary Science. 7: 213. doi: 10.3389/fvets.2020.00213 . PMC   7248982 . PMID   32509803.
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