Chemicals / Complex Chemical Agents/ Chemical:
Flunixin meglumine (with special reference to Ruminants, Hedgehogs, Elephants and Bears)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
Non-steroidal anti-inflammatory drug. (B263)

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Names and Formulae
Type Non-steroidal anti-inflammatory drug; a highly substituted derivative of nicotinic acid. (B263)
Alternative Names
  • 3-pyridine-carboxylic acid (chemical name). (B263, J4.194.w1)
  • 2-[[2-methyl-3-(trifluoromethyl)phenyl]amino]-, compd. with 1-deoxy-1-(methylamino)-D-glucitol (1:1). (J289.27S1.w1)
  • Flunixin
  • Finadyne (trade name).
Chemical Formula C14H11F3N2O2 C7H17NO5 (J289.27S1.w1)
Chemical Structure --
Molecular Weight 491.46. (J289.27S1.w1)
Related Chemicals --

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Physical Properties / Chemistry
Appearance

Crystalline powder, white to off-white. (J289.27S1.w1)

Melting point --
Boiling point --
Density --
Water solubility Soluble. (J289.27S1.w1)
Other solubility
  • In ethanol: soluble. (J289.27S1.w1)
  • In methanol: soluble. (J289.27S1.w1)
  • In ethyl acetate: practically insoluble. (J289.27S1.w1)
Acid/Base pKa 5.82 (J289.27S1.w1)

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Pharmacology & General Information
Pharmacology
  • Highly potent cyclo-oxygenase inhibitor. (B263)
  • "The precise site and mechanism of action is unknown." (J289.27S1.w1)
Storage / Stability
  • Store at 2-30C (36-86F) unless otherwise specified by the manufacturer. (B263, J289.27S1.w1)
  • Protect from freezing. (J289.27S1.w1)
Legal Category (In UK) POM (B350)

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5); Gracia Vila-Garcia (V.w67)
Referees Suzanne I. Boardman (V.w6); Becki Lawson (V.w26); Susan Mikota (V.w72)

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Therapeutic Information

Uses/Indications
Activity
  • Analgesic, anti-inflammatory and anti-pyretic activity. (B263, J4.194.w1)
    • Recommended for reducing inflammation and pain of both musculoskeletal and gastrointestinal problems. (J4.194.w1)
  • May improve the haemodynamics of animals with septic shock. (B263)

In mastitis:

  • In cows with experimentally induced Escherichia coli mastitis, intravenous injection of flunixin meglumine (1.1 mg/kg intravenously or 2.2 mg/kg intramuscularly) decreased the amount of kicking at the udder as well as decreasing the febrile response and preventing the decrease in ruminal contraction frequency and amplitude seen in untreated cows. (J3.124.w3)
  • Experimentally, repeated administration of flunixin meglumine at 1.1 mg/kg (initially intravenously, thereafter intramuscularly at eight-hour intervals) reduced pain as well as oedema, quarter size and quarter temperature in cows with endotoxin-induced mastitis. (J13.47.w1)
  • In cows with endotoxin-induced mastitis, injection with flunixin meglumine at 2.2 mg/kg intravenously after the onset of clinical signs of mastitis (rectal temperature > 40C and presence of mammary swelling) was found to increase rumen motility, decrease rectal temperature and reduce mean heart rate; it did not ameliorate either swelling of the mammary gland or loss of milk production. A specific effect on pain was not mentioned. (J13.65.w1)
  • In sheep with spontaneous acute clinical mastitis treatment with flunixin (100 mg per ewe, 1.82-2.33 mg/kg body weight) as well as antibiotic (cefuroxime) produced a significantly (P <0.01) greater rate of reduction of rectal temperature and total clinical reaction score (based on milk appearance, udder temperature, oedema, size and pain, attitude and appetite) as well as a significantly greater clinical cure rate at day two (P <0.01) and day four (P <0.05) than those treated with antibiotic alone. (J289.23.w1)
Appropriate Use In the UK:
  • Inflammation and pain. (B201.10.w10)
  • Endotoxic shock. (B201.10.w10)
  • May provide post-operative pain control comparative to that given by opioid analgesics. (B201.10.w10)

In cattle:

  • "In cattle, Finadyne Solution is indicated for the control of acute inflammation associated with respiratory disease. It has also been shown to have some benefit in the treatment of experimental acute bovine pulmonary emphysema (Fog Fever)." (B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)
  • "In cattle, Finadyne may be used as an adjunctive therapy in the treatment of acute mastitis"(B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)
  • Fever, endotoxin-associated inflammation. (J289.27S1.w1)
  • Adjunct therapy in sepsis. (J289.27S1.w1)

In sheep:

  • For relief of pain, including pain due to orthopaedic or abdominal surgery. (J15.22.w1)
Erinaceus europaeus - West European Hedgehog:
  • Analgesic and anti-inflammatory, particularly for toxaemia, severe inflammation of the lungs or myiasis. (B284.6.w6)
Approved uses USA:

Horse:

  • Alleviation of pain and inflammation associated with musculoskeletal disorders alleviation of visceral pain associated with colic. (B263)
Cattle:
  • Control of pyrexia associated with bovine respiratory disease and endotoxaemia; control of inflammation in endotoxaemia. (B263)
Limitations --
Notes Horse: 
  • No appreciable alteration of gastro-intestinal activity. (B263)

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability
  • Rapid absorption following parenteral administration to cattle, dogs, monkeys, pigs and rats; rapid and relatively complete absorption following oral administration in horses and rapid absorption following oral administration in dogs, rats and monkeys. (J289.27S1.w1)

Horse: 

  • Following oral administration rapid absorption and about 80% bioavailability; peak serum levels in 30 minutes, onset of action within two hours, peak response 12-16 hours, duration of action up to 36 hours. (B263)
Cattle: 
  • Following intramuscular administration to cows at 1.1 mg/kg the bioavailability was 76.0 % +/- 28 % (mean +/- standard deviation). (J13.51.w4)
  • Following oral administration to heifers at 2.2 mg/kg (in food), the bioavailability was 60%. The concentration in plasma was higher for up to 1.5 hour after intravenous administration compared to the concentration after oral administration (P<0.05); there were no significant differences in concentration from five hours to 30 hours. (J289.18.w2)

Sheep

  • In sheep following intramuscular administration at 1.1 or 2.2 mg/kg absorption and distribution was rapid as indicated by the maximum plasma concentration of the drug (5.9 +/- 0.47 g/mL, mean +/- SEM) occurring at the first sampling time (30 minutes) in four of six animals dosed at 1.1 mg/kg and at 45 minutes in the remaining animals, and by the first sampling time of 1 hour in animals given 2.2 mg/kg (maximum concentration 11.0 +/- 0.89 g/mL). Bioavailability was 70% following either dose. (J289.16.w1)

Note: Flunixin has been shown to bind to chopped hay suspended in aqueous buffer solution, although less binding was observed than for phenylbutazone. (J21.44.w2)

Distribution In cattle:
  • Following intravenous administration to cows at 1.1 mg/kg the distribution half-life was 0.16h (harmonic mean) and the steady-state volume of distribution was 0.40 +/- 0.11 L/kg. (J13.51.w4)
  • Following administration of flunixin intravenously at 2.2 mg/kg to one cow and one heifer the half-life for the distribution phase was 0.19 h (cow) and 0.29 h (heifer) and the volume of distribution (based on the area under the time-concentration curve) was 789 mL/kg (cow) and 764 mL/kg (heifer) while the volume of distribution at steady state was 419 mL/kg (cow) and 297 mL.kg (heifer). (J13.56.w1)
  • Following administration of flunixin at 1.1 mg/kg intravenously in heifers the distribution half-life was 0.294 h, volume of distribution 1.050 L/kg with a calculated volume of distribution at steady state of 0.5 L/kg. (J21.39.w1)
  • Following administration of flunixin intravenously at 2.2 mg/kg in calves, the half life for distribution (t1/2α) was 0.10 +/- 0.03 h (mean +/- SEM) and the calculated volume of distribution was 2.11 +/- 0.37 L/kg. (J13.56.w2)
  • In cattle with experimentally induced Escherichia coli mastitis, following administration of flunixin intravenously at 2.2 mg/kg 12 hours after administration of the bacteria (i.e. when clinical signs of mastitis had developed), the volume of distribution was 0.43-0.49 L/kg. (J289.25.w3)
In sheep:
  • In sheep following intravenous administration at 1 mg/kg distribution was rapid (distribution half-life t1/2π 2.29 min (harmonic mean); t1/2α 32.6 min (harmonic mean)) and the volume at steady state was 166.2 +/- 37.2 mL/kg (mean +/- SEM); following intravenous administration at 2 mg/kg the volume at steady state was 151.8 +/- 26.3 mL/kg and the distribution half-life t1/2π was 2.71 min (harmonic mean), t1/2α 39.9 min (harmonic mean). J289.16.w1)
  • In sheep following intravenous administration at 1.1 mg/kg, using tissue cages flunixin was detected in both exudate and transudate two hours after administration. While concentrations in exudate and transudate were lower than concentrations in plasma during the first eight hours after administration, they were higher than levels in plasma after this time and were detectable in exudate up to 32 hours after administration and in transudate up to 48 hours in most individuals. Maximum drug concentrations were detected in exudate at 5.50 +/- 0.73 h (maximum value 1.82 +/- 0.22 g/mL) and in transudate at 8.00 +/- 0.75 h (maximum value 1.58 +/- 0.30 g/mL). Concentrations were higher in exudate than in transudate while the drug was distributing into the tissue cages and vice versa after the point of maximum concentration. In individual animals, those in which drug penetration was faster and a higher maximum concentration of drug was reached were also those in which elimination of the drug was faster. Following correction for mean retention time, the ration of the AUC (area under the time concentration curve) was larger for exudate in relation to plasma than for transudate. (J289.21.w2)
Plasma Protein binding / Storage
  • Extent of plasma protein binding is unknown. (B263)
In cattle:
  • Following administration of flunixin intramuscularly at 2.2 mg/kg in cows the mean +/- SD plasma protein bound fraction was estimated as 99.36 +/- 0.24% at flunixin concentrations in plasma of 3 to 24 g/mL. (J13.56.w1)

In sheep:

  • Data from a tissue cage model of flunixin pharmacokinetics in sheep indicated that plasma protein binding may be less in sheep than in equines or cattle, since there was higher extravascular penetration into both exudate and transudate, suggesting more unbound drug available for penetration into both inflamed and non-inflamed tissue cage fluids. (J289.21.w2)

In goats:

  • In vitro, flunixin meglumine was 84.8 % protein bound. (J21.61.w3)

In horses:

  • In vitro, flunixin meglumine was 86.9 % protein bound. (J21.61.w3)

In dogs:

  • In vitro, flunixin meglumine was 92.2 % protein bound. (J21.61.w3)
Elimination Route
  • Unknown; in horses detectable in urine. (B263)

In cattle:

  • Hepatic route, mainly by biliary secretion. (J4.194.w1)
  • In milk:
    • In cattle with experimentally induced Escherichia coli mastitis, following administration of flunixin intravenously at 2.2 mg/kg 12 hours after administration of the bacteria (i.e. when clinical signs of mastitis had developed), either the drug was not detected in milk or only traces were detected; in one cow a concentration of 0.019 mg/L was detected eight hours after flunixin administration. (J289.25.w3)
    • Following administration at 2.2 mg/kg intravenously in a radiolabel study, background concentrations were obtained in milk by 72 hours after administration. (J4.211.w1)
    • In lactating cows, following administration at 1.1 mg/kg every eight hours, no residues were detected in milk (with a detection limit of 50 ng/mL). (J4.211.w1)
Elimination half-life / Clearance Rate
  • Horse: serum half-life about 1.6 hours.(B263)
  • Dog: serum half life about 3.7 hours. (B263)
  • Cattle:  
    • Serum half life about 8.1 hours (B263); eight hours. (B340.10.w10)
    • Following intravenous administration to cows at 1.1 mg/kg the elimination half-life was 3.14 h (harmonic mean) and the clearance was 2.51 +/-0.96 mL/kg/minute. Following intramuscular administration of 1.1 mg/kg the elimination half-life was 5.20 (harmonic mean). (J13.51.w4)
    • Following administration of flunixin at 1.1 mg/kg intravenously in heifers clearance was 90 mL/kg/h and the elimination half-life was 8.12 h. (J21.39.w1)
    • Following administration of flunixin intravenously at 2.2 mg/kg to one cow and one heifer the clearance was 142 mLLkg/h (cow), 122 mL/kg/h (heifer) and the elimination half-life was 3.8 h in the cow, 4.3 h in the heifer. (J13.56.w1)
    • Following administration of flunixin intramuscularly at 2.2 mg/kg in cows, either four times daily for two weeks or twice daily for two weeks, the half-lives calculated between 48 and 96 hours after the last injection were 24.2 to 30.5 hours (harmonic mean 27.4 hours) and 21 to 26.6 hours (harmonic mean 23.9 h) respectively. The drug remained detectable for an average of 8 days after the last injection (6.5, 11.3 and 9.3 days for the cows which had been injected four times daily and 6.5, 7.0 and 4.3 days for those injected twice daily. (J13.56.w1)
    • Following administration of flunixin intravenously at 2.2 mg/kg in calves, the half life for elimination (t1/2β) was 6.87 +/- 0.49h (mean +/- SEM) and the clearance was 0.20 +/- 0.03 L/kg/h. (J13.56.w2)
    • Following oral administration to heifers at 2.2 mg/kg (in food), the mean half-life (harmonic mean) was 6.2 h. (J289.18.w2)
    • Following intravenous administration to heifers at 2.2 mg/kg clearance was 115 +/- 11 mL/kg/h (Mean +/- SEM) with a range of 79 to 140 mL/kg/h (J289.18.w2)
    • In cattle with experimentally induced Escherichia coli mastitis, following administration of flunixin intravenously at 2.2 mg/kg 12 hours after administration of the bacteria (i.e. when clinical signs of mastitis had developed), the mean elimination half-life was 5.7-6.2 h and clearance was 0.13-0.14 L/h/kg. (J289.25.w3)
  • Sheep:
    • In sheep following intravenous administration at 1 mg/kg the elimination half-life t1/2β was 229.8 min (harmonic mean) and clearance Clb was 0.60 +/- 0.03 mL/kg/min (mean +/- SEM); following intravenous administration at 2 mg/kg the t1/2β was 205.9 (harmonic mean) and clearance Clb was 0.7 +/- 0.03 mL/kg/min. (J289.16.w1)
    • Following intravenous administration at 1.1 mg/kg in sheep, the elimination half-life t1/2β was 2.48 +/- 0.12 h (mean +/- SE); mean retention time in plasma was 3.20 +/- 0.18 h. Clearance was slow: 38.96 +/- 4.86 mL/kg/h. Elimination from tissue cages was much and significantly (P<0.05) slower than clearance from plasma; the mean retention time was 9.78 +/- 0.93 hours in exudate and 12.98 +/- 1.01 h in transudate. (J289.21.w2)
Drug Interactions
  • Physical compatibilities not known: avoid mixing with other drugs in the same syringe. (B263)
  • Use cautiously with highly protein-bound drugs (e.g. phenytoin, valproic acid, oral anticoagulants, other anti-inflammatory agents, salicylates, sulphonamides, sulfonylurea antidiabetic agents. (B263)
  • Use cautiously with warfarin, methotrexate, aspirin, other agents known to cause gastro-intestinal ulceration. (B263)
  • Theoretically may reduce the saluretic and diuretic effects of furosamide. (B263)

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Administration
Formulations available

UK:

  • Finadyne (Schering-Plough
    • Finadyne Injection for dogs (10 mg as flunixin meglumine BP (Vet) and 5 mg phenol Ph Eur as a preservative, per mL). For slow intravenous or subcutaneous injection. (B350)
    • Finadyne Paste, 10g paste containing flunixine meglumine (Vet) equal to 500 mg flunixin in an inert carrier. For oral administration in horses. (B350)
    • Finadyne Solution, containing 50 mg flunixin as flunixin meglumine BP (Vet) and 5 mg phenol as preservative, per mL. For intravenous injection in cattle and horses. (B350)
  • Cronyxin Injection (Bimeda UK) aqueous solution containing 50 mg flunixin as flunixin meglumine and 5 mg phenol preservative, per mL. For slow intravenous injection in cattle and horses. (B350)
  • Meflosyl (Fort Dodge Animal Health) aqueous solution containing 50 mg flunixin as flunixin meglumine USP and 5 mg phenol preservative, per mL. For intravenous injection in cattle and horses. (B350)
  • Binixin (Bayer, plc.) aqueous solution containing 50 mg flunixin as flunixin meglumine and 5 mg phenol preservative, per mL. (B350)
USA
Doses / Administration Routes / Frequencies Cranes:

Cattle:

  • 1.1-2.2 mg/kg by slow intravenous injection once daily or the same dose divided over two injections at 12 hour intervals. For up to three days. Rapid administration should be avoided. (B263)
  • For aseptic lameness in cattle 1.1 mg/kg, administer within 24 hours of the onset of signs in order to be effective (B263)
  • 2.2 mg/kg loading dose intravenously followed by 1.1 mg/kg every 8 hours suggested (B263, J4.191.w12, J21.39.w1)
  • For treatment of injury to the radial nerve, 250-500 mg intravenously or intramuscularly twice daily; only one treatment may be required. Taper the dose and discontinue usually after two to three days. (B263)
  • 2.2 mg/kg intravenously once daily for up to five days. For treatment of acute inflammatory conditions. (B201.10.w10)
  • 1.1 to 2.2 mg/kg intravenously or intramuscularly every 24 hours for three to five days. (J4.211.w1)
    • In France: 2 mg/kg, intravenously or intramuscularly. (J4.211.w1)
    • In Switzerland: 2.2 mg/kg intravenously or intramuscularly, at 24 hour intervals. (J4.211.w1)
  • "For use in bovine acute inflammatory conditions the recommended dosage is 2 ml Finadyne Solution per 45 kg bodyweight (equivalent to 2.2 mg flunixin per kg) injected intravenously and repeated as necessary at 24 hour intervals for up to 5 consecutive days." (B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)

Experimental data:

  • Multiple administration in lactating cows, at 1.1 mg/kg initially by intravenous injection subsequently at eight-hour intervals by intramuscular injection for six doses, produced a plasma concentration of about 1 g/mL two hours after each dose and approximately 0.5 g/mL immediately before the next dose. (J13.51.w4)
  • Following administration of 2.2 mg/kg flunixin the drug inhibited the oedema produced by intradermal injection of bradykinin (AUCeff 692.3 +/- 223.2 percent x h) lower than that produced by 2 mg/kg tolfenamic acid (AUCeff 1167.4 +/- 178.2 (SEM) percent x h) or (1159.2 +/- 195.6 Percent x h). The drug inhibited synthesis of PGE2 in exudate (in a tissue cage) over 24 hours (AUCeff 1651 +/_ 116 percent x h); values for ketoprofen and tolfenamic acid were similar at 1653 +/- 91 and 1279 +/- 179 respectively. Synthesis of LTB4 in exudate was not significantly inhibited by flunixin or the other two drugs. Flunixin inhibited release of β-glucuronidase for 30 hours (significantly longer than tolfenamic acid or ketoprofen), AUC 2129 +/- 143 percent x hour; tolfenamic acid inhibited release for up to 12 hours with AUCeff of 671 +/- 66 percent x h and ketoprofen inhibited release for up to 24 hours, AUCeff 1197 +/- 209 percent x hour. Concentrations of the exudate enzymes lactate dehydrogenase, acid phosphatase, serein protease, cysteine protease and mettaloproteases were not affected by any of the three drugs. Generation of O2- ions was affected in a dose dependent manner by all three drugs, with a significantly larger (P<0.05) inhibition for tolfenamic acid than for flunixin or ketoprofen. (J3.137.w7)
  • Following administration of 2.2 mg/kg flunixin, serum thromboxane B2 was significantly inhibited by 85 to 92% for 12 hours; exudate prostaglandin PGE2 was inhibited by 61 to 91% for 24 hours with maximum inhibition between six and nine hours, β-glucuronidae activity was inhibited by 70 to 88% and inhibition was statistically significant for up to 30 hours. Exudate concentration of leukotriene LTB4 and activities of the exudate enzymes lactate dehydrogenase, acid phosphatase, serein protease, cysteine protease and mettaloproteases were not significantly affected, although there were large variations between individual animals in protease activities. Bradykinin-induced swelling was inibited by 40 to 50% at 2.5 and 7.5 hours, decreasing to 30 to 36% at 10.5 and 25.5 hours. Plasma concentration causing 50% of maximal effect was calculated to be 0.024 +/- 0.004 g/mL for TXB2 inhibition, 0.74 +/- 0.006 g/mL for inhibition of PGE2, 0.064 +/- 0.040 for β-glucuronidase inhibition and 0.061 +/- 0.03 for inhibition of the effect of bradykinin injection. (J13.56.w2)
  • In cows with endotoxin-induced mastitis, flunixin at 1.1 mg/kg intravenously significantly reduced milk thrombaxane B2 concentrations in the endotoxin-treated quarter, compared with cows given a saline placebo, and plasma levels of 15-keto-13,14-dihidro-PGF. (J13.47.w2)
  • In cattle with experimentally induced Escherichia coli mastitis, following administration of flunixin intravenously at 2.2 mg/kg 12 hours after administration of the bacteria (i.e. when clinical signs of mastitis had developed), elimination of bacteria was enhanced, whether or not enrofloxacin was also given. Cattle given enrofloxacin (5 mg/kg intravenously initially followed by 5 mg/kg subcutaneously once daily for two more days) had higher milk yields than those given only the single injection of flunixin. (J289.25.w3)
  • In cattle with foot-and-mouth disease flunixin given at 2.2 mg/kg gave clinical improvement including easier locomotion, decreased pyrexia, increased feed intake and improved weight gain after the acute phase of the disease. The effects were considered to be due to the analgesic and antipyretic effects of flunixin. (J4.194.w1)
  • Oral administration:
    • When flunixin was administered to six heifers at 2.2 mg/kg either orally (in a small amount of food) or intravenously, biosynthesis of prostaglandin PGF2α, measured by concentration of a major metabolite of the prostaglandin, was significantly inhibited, by 30 minutes after intravenous and by 60 minutes after oral administration. There were no significant differences between the effects from oral or intravenous administration up to eight hours after dosing; from 10 hours onwards the effect was greater for oral dosing and the effect lasted more than 30 hours after oral administration and was generally shorter after intravenous administration. The conclusion of the study was that flunixin could be given orally as an alternative to intravenous dosing in cattle. (J289.18.w2)
    • Either oral (granules in food) or intravenous flunixin at 2.2 mg/kg prior to administration of endotoxin to produce endotoxaemia significantly reduced (P<0.05) the increase in rectal temperature seen in individuals given endotoxin without pre-treatment with flunixin from 2.5 to 6.5 hours after endotoxin administartion and significantly reduced (P<0.05) the increase in plasma concentration of a prostaglandin PGF2α metabolite seen following endotoxin administration. The study suggested that oral administration of flunixin granules could be used as an alternative to parenteral administration in cattle. (J13.57.w4)

Sheep:

  • 1.1 mg/kg intravenous or intramuscular injection is "effective and safe". (B217.69.w69)
  • 2.2 mg/kg intravenously for three days. Note: this is not licensed for use in sheep in the UK. (J15.17.w3)
  • 2 mg/kg intravenously may be used to provide pain relief for 12 to 24 hours, for example following orthopaedic or abdominal surgery. (J15.22.w1)
  • 2 to 4 mg/kg intravenously. Duration of action 12-24 hours. May be better regarded in sheep as an anti-inflammatory rather than an analgesic. (P53.24.w1)
  • 2 mg/kg subcutaneously or intravenously daily. (B322.5.w5)
  • 1.1 mg/kg or 1.0 mg/kg suggested, based on concentrations obtained in plasma, transudate and exudate following intravenous administration in sheep being higher following this dosage than with a dose of 2.2 mg/kg in cattle, although with the proviso that "this must be supported with efficacy and toxicity data." (J289.21.w2)

Experimental data:

  • Flunixin meglumine given at 2.2 mg/kg intramuscularly daily for five days gave plasma concentrations four hours after administration of 3.3 +/- 0.3 g/mL to 5.3 +/- 0.8 g/mL. (J289.16.w1)
  • Flunixin meglumine given intramuscularly at 2 mg/kg in sheep did not produce any significant change in the nociceptive threshold measured by an electrical stimulus over a period of at least 40 minutes; it had no measurable effect on the response of the sheep to electrically induced pain. (J24.73.w1)
  • While doses of 1.0 mg/kg or 2.0 mg/kg flunixin intravenously had no effect on the thresholds to noxious mechanical stimulation in normal or lame sheep tested over six hours and 30 minutes respectively, repeated administration of 1.0 mg/kg flunixin over three days in sheep suffering from footrot significantly reduced their thresholds to noxious mechanical stimulation, bringing them down to levels similar to those seen in the control normal sheep. This may have been due to the analgesic and anti-inflammatory actions of the flunixin making the sheep less reluctant to raise one foot and thus bear weight on the opposite foot which was generally also affected by footrot. (J21.58.w1)
  • Flunixin administered at 1.0 mg/kg 30 minutes prior to the application of a tourniquet in adult male neutered Suffolk-cross sheep attenuated the development of mechanical hyperalgesia seen after application of the tourniquet; thresholds to noxious mechanical stimulation were not significantly different from control values in sheep given flunixin, whereas they were significantly reduced at 10, 15 and 20 minutes after application of a tourniquet without any analgesic. (J21.57.w1)
  • Flunixin at 2.2 mg/kg in adult female crossbred sheep significantly increased (P=0.002) the threshold of healthy sheep to a noxious mechanical stimulus, from 4.59 +/- 0.27 N to a maximum of 8.31 +/- 0.94 N at 30 minutes after administration of flunixin; thresholds returned to control levels by 2.5 hours after flunixin administration. In lame sheep given flunixin the thresholds were again significantly increased following administration of flunixin, but there was no obvious peak to the effect. Concentrations of the thromboxane TxB2 were significantly reduced from 0.77 +/- 0.24 ng/mL by about 65% at 30 minutes after flunixin administration and by 81% at 60 minutes. (J289.18.w3)
  • Flunixin given at 2.2 mg/kg intravenously daily for three days "showed some potential for reduction of pulmonary effects" in an experimental model of acute bovine pulmonary emphysema. (J289.27S1.w1)

Goats:

  • 1.0 mg/kg once. (B322.5.w5)

Experimental data:

  • In vitro flunixin had 50% of its maximum inhibitory effect on serum thromboxane B2 production at 0.02 M and the maximum inhibitory effect was at 0.14 M. However in vivo activity may differ from the in vitro values. (J21.61.w3)

Erinaceus europaeus - West European Hedgehog:

  • Hedgehog-specific dose not established. (B267)
  • 2 mg/kg subcutaneously or orally once daily. Analgesic and anti-inflammatory, particularly for toxaemia, severe inflammation of the lungs or myiasis .(B284.6.w6)
  • 2 mg/kg intramuscularly once daily. Maximum five days of therapy. (D93)

Elephants:

Loxodonta africana - African Elephant

  • 1 g daily for three days was given in a juvenile elephant. (J4.185.w1)
  • 3 g intramuscularly perioperatively was administered in a 17 year-old female. (J3.152.w2)

The following information is taken with permission directly from the Elephant Care International website (W580.Aug2005.w13):

Elephants:

a) Anecdotal doses of 1 mg/kg every 24 hours (route of administration not specified) have been reported. This is based on a survey of 20 zoo veterinarians in the U.S. (Mortenson, 1998, 1998, 2001).

 

  Elephant References:

a) Mortenson,J., 2001. Determining dosages for antibiotic and anti-inflammatory agents. In: Csuti,B., Sargent,E.L., and Bechert,U.S. (Editors), The Elephant's Foot. Iowa State University Press, Ames pp. 141-144

a) Mortenson,J. 1998. Determining dosages for anti-inflammatory agents in elephants. Proceedings AAZV and AAWV Joint Conference. Pages: 477-479

a) Mortenson,J. and Sierra S. 1998. Determining dosages for antibiotic and anti-inflammatory agents in elephants. Proceedings of the First North American Conference on Elephant Foot Care and Pathology. Pages: 50-55

Bears:

  • In general: "Domestic dog drugs and dosages are used to treat bears." (B336.51.w51)
  • 1.0 mg/kg subcutaneously has been given for postoperative analgesia. (J2.30.w4)

Dogs:

  • 0.5-2.2 mg/kg intramuscularly or intravenously once. (B263)
  • For surgical pain, 1 mg/kg intravenously, subcutaneously or intramuscularly once, subsequent doses 1 mg/kg. (B263)
Monitoring parameters
  • Analgesic, anti-inflammatory and anti-pyretic effects. (B263)
  • In dogs: gastro-intestinal effects. (B263)
  • In horses, if used chronically, complete blood counts, occult blood in faeces. (B263)

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Withdrawal period / Withholding time
Notes
  • Cattle: 
    • UK:
      • Milk 12 hours, slaughter seven days (Binixin Injection 5% (Bayer), Cronyxin injection (Bimeda UK), Meflosyl 5% injection (Fort Dodge Animal Health), Resprixin (Intervet)). (UK)(B201.10.w10)
      • Milk 12 hours, slaughter five days (Finadyne Solution (Schering-Plough)). (UK)(B201.10.w10, B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)
      • Milk 36 hours, slaughter seven days (Flunixin injection (Norbrook)). (UK) (B201.10.w10)
    • Australia:
      • Milk 36 hours slaughter 28 days (Cronyxin Injection, Bimeda) (Australia). (B201.10.w10)
      • Milk seven days, slaughter 28 days (Flumav (Mavlav) (Australia). (B201.10.w10)
      • Milk 36 hours slaughter 28 days (Flunix (Parnell) (Australia). (B201.10.w10)
    • Eire:
      • Milk 36 hours, slaughter seven days (Binixin Injection (Bayer), Finadyne solution (Schering-Plough), Flunixin Injection (Norbrook) (Eire). (B201.10.w10)
    • France: 
      • Milk withdrawal nil, meat 10 days, following administration at 2 mg/kg, intravenously or intramuscularly. (J4.211.w1)
    • Switzerland: 
      • Milk withdrawal 71 hours, meat withdrawal five days, following administration at 2.2 mg/kg intravenously or intramuscularly, at 24 hour intervals. (J4.211.w1)
    • New Zealand:
      • Milk nil, slaughter one day (Finadyne (Schering-Plough), Flunix (Parnell)). (New Zealand) (B201.10.w10)
      • Milk discard during treatment, slaughter one day. (Croayxin (Reamor)). (New Zealand) (B201.10.w10)
    • Note: If injected repeatedly intramuscularly the half-life is prolonged and the residue withdrawal periods may be lengthened. (J289.27S1.w1)
    • USA: 
      • Meat four days, when administered at a dose rate of 2.2 mg/kg bodyweight daily or 1.1 mg/kg bodyweight every 12 hours for a maximum of three days. (J289.27S1.w1)
      • Not labelled for use in lactating or dry dairy cows or in calves which are to be processed for veal. (J289.27S1.w1)
      • Following use at 1.1 to 2.2 mg/kg intravenously or intramuscularly every 24 hours for three to five days, withdrawal times suggested by FARAD of 72 hours for milk, 10 days for meat. [1997] (J4.211.w1)
    • Canada:
      • "If flunixin is administered to lactating dairy cattle at an intravenous dose of 2.2 mg per kg of body weight a day for three days, evidence has been compiled by the Canadian gFARAD that suggests a meat withdrawal time of 6 days and a milk withholding time of 72 hours would be sufficient to avoid residues." (J289.27S1.w1)
  • Horses: 
    • Slaugher 28 days (UK). (B201.10.w10)
    • Slaughter seven days (except Finadyne paste (Schering-Plough) "should not be used in horses for human consumption". (Eire) (B201.10.w10)
    • Slaughter periods vary from one day to 28 days for formulations from different manufacturers (New Zealand). (B201.10.w10)
    • Should not be used in horses intended for human consumption. (USA). (B201.10.w10)

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • "Do not exceed the stated dose or the duration of treatment." (B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)
  • Contraindicated in individuals with a history of hypersensitivity to the drug. (B201.10.w10, B263, B350, (J289.27S1.w1)
  • Caution may be advisable when using in individuals with pre-existing gastro-intestinal ulcers, renal disease, hepatic disease, haematological disease. (B263)
  • Contraindicated in individuals with cardiac, renal or hepatic disease. (B201.10.w10, B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)
    • Use in individuals with cardiac, hepatic or renal disease should be considered carefully on a risk-benefit basis. (J289.27S1.w1)
  • Avoid using in individuals with dehydration, hypovolaemia or hypotension. (B201.10.w10)
  • Use in individuals with dehydration should be considered carefully on a risk-benefit basis, since dehydration may increase the risk of renal toxicity from NSAIDs. (J289.27S1.w1)
  • Avoid using concurrently with potentially nephrotoxic drugs. (B201.10.w10, B350)
  • "Avoid intra-arterial injection." (B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)
  • "Do not administer other NSAIDs concurrently or within 24 hours of each other." (B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)
    • Concurrent use of more than one NSAID may increase the risk of severe gastrointestinal side effects such as ulceration or haemorrhage. (J289.27S1.w1)
  • Contraindicated in individuals in which there is a possibility of gastro-intestinal ulceration or bleeding. (B201.10.w10, B350, J289.27S1.w1)
  • Contraindicated as a treatment concurrent with (or within 24 hours of) other NSAIDs. (B201.10.w10)
  • "It is preferable that NSAIDs which inhibit prostaglandin synthesis are not administered to animals which are undergoing general anaesthesia until fully recovered." (B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)"
  • Should not be used, except under special circumstances, in individuals with bleeding disorders, since NSAIDs are associated with platelet aggregation inhibition, thus their use in such patients could increase risk of adverse effects. (J289.27S1.w1)
  • "Do not use in hypovolaemic animals, except in the case of endotoxaemia or septic shock." (B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)
  • In cats: usually considered to be contraindicated. (B263)
  • Use with caution in pregnancy (no records of reproductive problems, but may not have been fully evaluated for safety). (B201.10.w10, B263)
  • In horses with colic: repeated use risks masking behavioural and cardiopulmonary signs associated with intestinal devitalisation or endotoxaemia. (B201.10.w10, B263)
  • Horses: contraindicated in racehorses prior to racing. (B201.10.w10)
  • Contraindicated in mares during pregnancy. (B201.10.w10); contraindicated in pregnant animals. (B340.10.w10)
    • "Do not administer to pregnant mares; safety studies in pregnant mares have not been conducted." (B350: data sheet for Finadyne Solution, Schering-Plough Animal Health)
  • Contraindicated in individuals undergoing general anaesthesia until consciousness has been regained. (B201.10.w10)
  • "Some NSAIDs may be highly bound to plasma proteins and compete with other highly bound drugs which can lead to toxic effects." (B350)
    • Flunixin is highly plasma protein bound, it is therefore possible that either this drug may displace other drugs from their protein binding sites or that flunixin may be displaced by other drugs, leading, in either case, to increased action of whichever drug has been displaced. (J289.27S1.w1)
  • "Administration of flunixin to bulls intended for breeding is not recommended because reproductive effects have not been studied." (J289.27S1.w1)
  • "In cows, nonsteroidal antiinflammatory drugs have the potential to affect the onset of the estrus cycle or of parturition." (J289.27S1.w1)
Adverse Effects / Side Effects / Warnings
  • Intra-arterial injection should be avoided: this may result in CNS stimulation (hysteria), ataxia, hyperventilation, muscle weakness. (B263)
  • Use with care in very young (less than six weeks old) or old animals. (B201.10.w10)
  • In horses: 
    • Intramuscular injection may result in local swelling, induration, stiffness and sweating. (B263)
      • Rarely, infections, including clostridial, have been seen in association with local tissue reactions to intramuscular injection. (J289.27S1.w1)
    • Potentially gastrointestinal intolerance, hypoproteinaemia, haematological abnormalities. (B263)
      • Unlikely to cause oral or gastric ulceration when administered at the recommended dose for a period of two weeks. (J289.27S1.w1)
    • Rarely anaphylactic-type reactions recorded, usually following rapid intravenous injection. (B263)
  • In dogs: 
    • Gastrointestinal distress with vomiting, diarrhoea, ulceration (high or chronic dosing). (B263)
    • Anecdotal reports of pre-operative use at high doses causing renal shutdown. (B263)
    • Very occasionally may precipitate acute renal failure: should not be given post-operatively until the patient has regained consciousness. (B201.10.w10)
  • In cattle: 
    • Intramuscular administration is not recommended; local tissue reactions may occur if this route is used. (J289.27S1.w1)
      • Intramuscular injection in cows at 2.2 mg/kg resulted in slight reactions of pain and there were some palpatory findings [pain, high skin temperature and oedema were used for assessment] which were not present following injection of physiological saline. A rise in serum creatine kinase was detected which was significantly higher than that seen following injection of saline (no rise), ketoprofen or metamizole but not significantly different from that seen with injection of phenylbutazone. (J307.40.w1)
    • Haematochezia and haematuria have been reported following administration in cattle for longer than the recommended maximum of three days. (J289.27S1.w1)
    • Rarely anaphylactic-type reactions recorded, usually following rapid intravenous injection. (B263, J289.27S1.w1)
Operator Warnings --
Overdose / Acute Toxicity
  • No clinical reports. (B263)

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Detailed Toxicological Information
Classification --
Acute Toxicity --
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Sources in the Environment
Natural sources --
Human-associated sources --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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