Chemicals / Complex Chemical Agents/ Chemical:

Carprofen (with special reference to Ruminants, Hedgehogs, Bears, Lagomorphs, Ferrets and Great Apes)

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 NSAID (non-steroidal anti-inflammatory drug); derivative of propionic acid. (B263); in the aryl-propionic acid group of NSAIDs. (J289.27S1.w1)
Alternative Names (+)-6-Chloro-alpha-methylcarbazole-2-acetic-acid. (J289.27S1.w1); Rimadyl (Pfizer Limited). (B266)
Chemical Formula C15H12ClNO2. (J289.27S1.w1)
Chemical Structure Commercially available carprofen is a racemic mixture of the S (+) enantiomer (more potent as an anti-inflammatory) and the R (-) enantiomer. (B263)
Molecular Weight 273.72. (J289.27S1.w1)
Related Chemicals Ketoprofen, ibuprofen and naproxen are also propionic acid derivative NSAIDs. (J289.27S1.w1)

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Physical Properties / Chemistry
Appearance

White, crystalline. (B263, J289.27S1.w1)

Melting point --
Boiling point --
Density --
Water solubility
  • Practically insoluble at 25C. (B263, J289.27S1.w1)
Other solubility
Acid/Base --

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Pharmacology & General Information
Pharmacology
  • Inhibits cyclo-oxygenase, phospholipase A2 and prostaglandin synthesis. (B263)
    • Weak inhibitor of cyclo-oxygenase. (B201.10.w10, J35.152.w4)
  • The mechanisms of action of carprofen are not clear. (J35.152.w3, J35.152.w4, J289.27S1.w1)
  • At a dosage of 4 mg/kg in sheep, both racemic and S(+) carprofen effectively inhibited cyclooxygenase (COX) isoenzymes, suggesting that at this dose rate at least part of the effect of carprofen is via inhibition of COX. (J289.26.w2)
  • Racemic carprofen at 4 mg/kg or S(+) enantiomer carprofen at 2 mg/kg was shown to be a potent inhibitor of cyclooxygenase in vivo in sheep. (J13.63.w1)
  • Note: chiral inversion of the enantiomers of carprofen apparently does not occur in various species including humans, dogs, horses, cattle, rats and cats. (J289.20.w2, J289.27S1.w1)
Storage / Stability
  • Store at room temperature (15-30C). (B263)
Legal Category (In UK) POM (B266)

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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)
Referees Suzanne I. Boardman (V.w6)

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Therapeutic Information

Uses/Indications
Activity
  • Analgesic, anti-inflammatory and antipyretic activity. (B263, J289.27S1.w1)
  • Note: The S(+) enantiomer has considerably higher activity than the R(-) enantiomer, with a potency ration in various in vitro and in vivo tests of 3.8 to more than 24. (J289.20.w2)
Appropriate Use
  • Inflammation, pain. (B201.10.w10, B263)
  • May provide post-operative pain control comparative to that given by opioid analgesics. (B201.10.w10)
  • In calf pneumonia to suppress pulmonary oedema. (B201.10.w10)
  • In young cattle less than 12 months old "indicated as an adjunct therapy for the control of acute inflammation associated with respiratory disease." (B266)
  • Unlike other NSAIDs, use during or prior to anaesthesia, or in individuals with pre-existing renal disease, is not contra-indicated. This drug is licensed for preoperative use. (B322.3.w3)
Limitations Not labelled for use in food-producing animals in the USA or Canada. (J289.27S1.w1)
Notes --

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability
  • Dog: oral administrated carprofen is about 90% bioavailable; peak serum levels at one to three hours after administration.
  • Following administration of carprofen to lactating cows at 0.7 mg/kg intravenously daily for five days peak plasma concentrations, reached following the fifth injection, were about 45 g/mL. (J171.131.w2)
Distribution

Cattle:

  • Following administration to healthy cows at 0.7 mg/kg bodyweight t1/2α was 1.81 +/- 0.36 h (mean +/- SEM) and the volume of distribution at steady state Vdss was 0.091 +/- 0.003 L/kg. In the same cows with endotoxin induced mastitis, t1/2α was 1.01 +/- 0.16 h (mean +/- SEM) (significantly lower, P<0.05) and the volume of distribution at steady state Vdss was 0.086 +/- 0.004 L/kg. (J289.14.w2)
  • Following administration to calves of eight to 10 weeks old at 0.7 mg/kg, the half-life of the distribution phase, t1/2α  was 0.828+/- 0.264 h (mean +/-SEM); values for the R(-) and S(+) enantiomers were not significantly different from one another: 0.883 +/- 0.247 h and 0.742 +/- 0.261 h respectively. The volume of distribution (area method) Vd(area) was 151.8 +/4.3 mL/kg for total carprofen and was significantly (P<0.01) lower for R(-) than for S(+) carprofen, with values of 144.8 +/- 4.8 mL/kg and 162.3 +/- 2.5 mL/kg respectively. Volume of distribution at steady state (Vdss) for total carprofen was 154.7 +/- 2.7 mL/kg and again was significantly (P<0.001) lower for R(-) than for S(+) carprofen with values of 147 +/- 3.4 mL/kg and 162.8 +/- 2.2 mL/kg respectively. (J35.152.w3)
  • Following administration to calves of 16-17 weeks old at 0.7 mg/kg, the half-life of the distribution phase, t1/2α was 0.546+-0.081 h (mean +/-SEM); values for the R(-) and S(+) enantiomers were not significantly different from one another: 0.624 +/- 0.089 h and 0.476 +/- 0.067 h respectively. The volume of distribution (area method) Vd(area) was 147.0 +/- 4.4 mL/kg for total carprofen and was significantly (P<0.01) lower for R(-) than for S(+) carprofen, with values of 136.2 +/- 2.9 mL/kg and 154.4 +/- 5.4 mL/kg respectively. Volume of distribution at steady state (Vdss) for total carprofen was 146.0 +/- 5.0 mL/kg and again was significantly (P<0.05) lower for R(-) than for S(+) carprofen with values of 140.2 +/- 4.2 mL/kg and 154.0 +/- 7.5 mL/kg respectively. In tissue cages, penetration into transudate was poor while penetration into exudate was good, for both enantiomers. (J35.152.w4)
  • Following administration of carprofen to lactating cows at 0.7 mg/kg, the volume of distribution was 0.09 L/kg. (J171.131.w1)

Sheep:

  • Following intravenous administration of racemic carprofen at either 0.7 mg/kg or 4.0 mg/kg to adult Suffolk cross sheep, the volume of distribution was small: Vd(area) was found to be 95.5 +/- 5.95 mL/kg (mean +/- SEM) and 118.4 +/- 3.53 respectively with volume of distribution at steady state Vd(ss) 92.7 +/- 5.77 mL/kg and 117.3 +/- 3.31 mL/kg respectively. It was commented that this indicated carprofen is not widely distributed throughout the body, and is probably related to high plasma protein binding. (J21.53.w2)
  • Following intravenous administration in sheep of 4 mg/kg racemate carprofen, the half-life of the distribution phase, t1/2α was 0.36 +/- 0.10 h (mean +/- SD) for R(-) and 0.43 +/- 0.09 h for S(+) while the volume at steady state Vss was 122.1 +-14.6 mL/kg and 128.7 +/- 18.7 respectively; after administration of the individual enantiomers at 2 mg/kg the half-life of the distribution phase, t1/2α was 0.31 +/- 0.16 h (mean +/- SD) for R(-) and 0.56 +/- 0.61 h for S(+) while the volume at steady state Vss was 117.9 +/- 10.5 mL/kg and 127.3 +/- 13.7 mL/kg respectively. (J289.26.w2)
Plasma Protein binding / Storage Carprofen is highly plasma protein bound. (J21.53.w2)
  • Dog: highly (99%) plasma protein-bound. (B263)
Elimination Route
  • Metabolised in the liver, mainly by glucuronidation and oxidative processes. (B263)
  • About 70-80% eliminated in faeces. (B263)
  • About 10-20% eliminated in urine. (B263)
  • Some enterohepatic recycling. (B263)
  • Mainly eliminated by biotransformation in dogs, horses, rats and sheep, with both enantiomers converted to glucuronide metabolites. (J289.27S1.w1)

Cattle:

  • In milk: Following administration to healthy cows or cows with endotoxin-induced mastitis at 0.7 mg/kg bodyweight, concentrations in milk of healthy cows was below the detection limit of the assay used (i.e. below 0.022 g/mL milk) but concentrations in milk from the inflamed mastitic quarters were increased, up to 0.164 +/- 0.024 g/mL, in the first 12 hours after induction of mastitis but were still lower than in plasma. Concentrations were reduced back to below 0.022 g/mL milk at 24 to 48 hours. It was suggested that the increased concentration in mastitic milk may be due to damage to the blood/milk barrier. (J289.14.w2)
  • In milk. Following administration of carprofen to lactating cows at 0.7 mg/kg daily for five days the concentration in milk was generally less than the sensitivity limit of the test used (25 ng/mL) and rarely reached 30 ng/mL in a few samples collected after the fourth or fifth injection. The data was considered to indicate poor excretion into milk. (J171.131.w1)
Elimination half-life / Clearance Rate Elimination half-life:
  • Dog: approximately 13-18 hours (the S enantiomer has a longer half life than the R enantiomer). (B263)
  • Horse: reported to be 22 hours. (B263)
  • Human: 12 hours. (B135)
  • Horse: S(+) 15 hours; R (-) 32 hours. (B340.10.w10)
  • Cattle: S(+) 37 hours; R (-) 50 hours. (B340.10.w10)
  • Dog: mixed drug 8-15 hours. (B340.10.w10)
  • Cat: S(+) 15 hours; R (-) 20 hours. (B340.10.w10)

Cattle:

  • Following administration to healthy cows at 0.7 mg/kg bodyweight there was a long elimination half-life (30.7 +/- 2.3 h) and a relatively low systemic clearance of 2.4 +/- 0.16 mL/h kg. In the same cows with endotoxin-induced mastitis, the elimination half life was significantly (P<0.01) longer at 43.0 +/- 2.3 h and the clearance was significantly lower (P<0.01) at 1.4 +/- 0.13mL/h kg. (J289.14.w2)
  • Following administration to calves of eight to 10 weeks old at 0.7 mg/kg, the half-life of the elimination phase, t1/2 β  was 43.4 +/- 2.3 h (mean +/-SEM); values for the R(-) and S(+) enantiomers were significantly (P<0.01) different from one another: 49.8 +/- 3.9 h and 37.4 +/- 2.4 h respectively. Clearance for total carprofen was 2.492 +/- 0.171 mL/h/kg and clearance was significantly (P<0.001) lower for R(-) than for S(+) with values of 2.073 +/- 0.145 mL/h/kg and 3.075 +/- 0.221 mL/h/kg respectively. (J35.152.w3)
  • Following administration to calves of 16-17 weeks old at 0.7 mg/kg, the half-life of the elimination phase, t1/2β  was 33.8 +/- 1,7 h (mean +/-SEM); values for the R(-) and S(+) enantiomers were significantly (P<0.01) different from one another: 37.7 +/- 1.8 h and 29.1 +/- 1.6 h respectively. Clearance for total carprofen was 2.984 +/- 0.094 mL/h/kg and clearance was significantly (P<0.001) lower for R(-) than for S(+) with values of 2.524 +/- 0.098 mL/h/kg and 3.696 +/- 0.113 mL/h/kg respectively. (J35.152.w4)
  • Following repeated administration of carprofen to lactating cows at 0.7 mg/kg daily for five days, the elimination half life was in the range 44.5 to 64.6 h. Clearance after a single injection was 9.0 mL/min. (J171.131.w1)

Sheep: 

  • Following intravenous administration of racemic carprofen at either 0.7 mg/kg or 4.0 mg/kg to adult Suffolk cross sheep, the elimination half-life t1/2β was long at 26.1 h +/- 1.14 h (mean +/- SEM) and 33.7 h +/- 3.14 h respectively. Clearance Clb was slow: 2.5 +/- 0.1 mL/kg/h and 2.5 +/- 0.3 mL/kg/h respectively. Clearance in sheep may be slower than in other species. (J21.53.w2)
  • Following intravenous administration in sheep of 4 mg/kg racemate carprofen or 2 mg/kg of either enantiomer, the drug was detectable in plasma consistently from five minutes to 144 hours after injection. After administration of the racemate the elimination half-life t1/2β was 66.36 +/- 21.81 h (mean +/- SD) for R(-) and 24.17 +/- 5.98 for S(+); after administration of the individual enantiomers t1/2β was 58.75 +/- 11.78 h and 25.09 +/- 5.50 for the R(-) and S(+) enantiomers respectively. After administration of the racemate, clearance CLB was 1.42 +/- 0.36 mL/kg/h for R(-) and 4.00 +/- 1.22 mL/kg/h for S(+); after administration of the individual enantiomers clearance was 1.53 +/- 0.30 mL/kg/h for R(-) and 3.77 +/- 1.04 mL/kg/h for S(+). (J289.26.w2)
Drug Interactions
  • May displace other drugs which are highly plasma protein-bound; could result in increased serum levels and duration of action for phenytoin, valproic acid, oral anticoagulants, other anti-inflammatory drugs, salicylates, sulfonamides, sulfonylurea antidiabetic agents. (B263)
  • Use concurrently with aspirin may result in lowered plasma levels of carprofen and increased likelihood of gastro-intestinal effects with blood loss. (B263)
  • Significant increase in both serum levels and half life of carprofen may be seen if probenecid is administered. (B263)
  • Severe toxicity has been recorded with concurrent use of NSAIDs and methotrexate. (B263)
  • May reduce the saluretic and diuretic effects of furosamide. (B263)
  • May increase serum levels of digoxin. (B263)

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Administration
Formulations available
  • Rimadyl (Pfizer Limited). 
    • Rimadyl Granules: "White, free-flowing granules containing carprofen 8.75% w/w". (B266)
    • Rimadyl Small Animal Injection: "clear, sterile, mixed micelle solution for injection, containing 50 mg carprofen per ml (5% w/v) with Benzyl alcohol PhEur (1% w/v) as preservative." (B266)
    • Rimadyl Large Animal Solution: "clear, very pale straw coloured, sterile, aqueous solution for parenteral injection containing carprofen 5% w/v (50 mg/ml) with Ethanol PhEur 10% w/v as preservative." (B266)
    • Rimadyl Tablets: "round white tablets scored down the middle containing as active ingredient either 20 mg or 50 mg carprofen." (B266)

Note: preparations contain racemic mixture R and S enantiomers in 50:50 mix. (B340.10.w10, J289.27S1.w1)

Doses / Administration Routes / Frequencies

Cattle:

  • 1.4 mg/kg as a single dose, by subcutaneous or intravenous injection. (UK)(B340.10.w10)
  • 1.4 mg/kg (Eire)(B201.10.w10)
  • 1.4 mg/kg (1 mL of 5% w/v solution per 35 kg) subcutaneously or intravenously, administered once. (B266)

Experimental data:

  • In cows with experimentally induced Escherichia coli endotoxin mastitis, treatment with a single dose of carprofen (0.7 mg/kg intravenously), given two hours after endotoxin administration, when the affected quarter was clearly swollen and body temperature was raised, significantly reduced clinical signs of mastitis including swelling of the quarter (p<0.01), rectal temperature (p<0.001), heart rate (P<0.01) and general depression (P<0.01). (J289.14.w2)
  • In calves of eight to 10 weeks old, administration of carprofen at 0.7 mg/kg intravenously attenuated the temperature rise which occurred in response to injection of carrageenin or dextran, although the effects were not statistically significant at most sampling times; skin swelling due to these substances was attenuated by carprofen but the effect was not statistically significant. Carprofen also reduced ex vivo serum thromboxane B2 synthesis but the effect was slight and was not significant at most sampling times. (J35.152.w3)
  • In calves of 16 to17 weeks old, administration of carprofen at 0.7 mg/kg intravenously did not inhibit synthesis of prostaglandin PGE2 in exudate in a tissue cage; 12-hydroxyeicosatetraenoic acid concentrations were reduced, indicting partial inhibition of 12-lipoxygenase, but this effect was generally not statistically significant. (J35.152.w4)
  • Administration of carprofen to post-partum cows at 0.7 mg/kg intravenously daily for five days was considered to be well tolerated by all the cows. The drug significantly (P<0.05) reduced plasma levels of 15-keto-13,14-dihydro-prostaglandin F2 alpha (the primary metabolite of the prostaglandin PGF2α); levels were 28-47% of pre-treatment values, compared with levels of 64-101% of pre-treatment values in control cows. This effect was seen from immediately after administration of carprofen and was at its maximum at three to six hours after injection: 60-80% inhibition at this time after the first injection and 40-85% inhibition at this time after the fifth daily injection. It was considered that the data showed that a single dose of 0.7 mg/kg carprofen intravenously effectively suppresses release of PGF2αs in the post-partum cow. (J171.131.w2)

Sheep:

  • 4 mg/kg subcutaneously for prolonged post-operative analgesia. (B217.69.w69)
  • 1 mg/kg intravenously once pre-operatively before caesarean section. (Note: not licensed for use in sheep in the UK).[2000](J15.22.w2)
  • 1.5-2.0 mg/kg by subcutaneous or intravenous injection once daily. (B322.5.w5)

Experimental data:

  • Carprofen administered at 0.7 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 carprofen, whereas they were significantly reduced at 10, 15 and 20 minutes after application of a tourniquet without any analgesic. (J21.57.w1)
  • Carprofen at 0.7 mg/kg maintained plasma levels at or higher than 1.5 g/mL (the level required to produce analgesia in the horse) for up to 48 hours. (J21.53.w2)
  • At a dosage of 4 mg/kg racemic carprofen or 2 mg/kg S(+) carprofen in sheep, the maximum inhibitory effect on serum thromboxane (TXB2) was greater than 99% and that on exudate prostaglandin (PGE2) was greater than 95%. The S(+) carprofen concentrations producing 50% of the maximum inhibitory effects were, following injection of the racemate, 9.39+/- 2.24 (mean +/- SD) g/mL for TXB2 inhibition in serum and 1.76 +/- 1.08 g/mL for inhibition of exudate PGE2; following injection of the S(+) enantiomer alone the values were 13.29 +/- 7.67 g/mL and 2.11 +/- 0.79 respectively. (J289.26.w2)
  • Following intravenous administration of 4 mg/kg racemic carprofen or 2 mg/kg S(+) carprofen in sheep, serum thromboxane 2 (TXB2) and exudate prostaglandin PGE2 generation was significantly inhibited for 32 hours, with a 50 to 98% reversible inhibitory effect. Administration of R(-) carprofen at 2 mg/kg intravenously significantly attenuated serum TXB2 generation but did not affect exudate PGE2 production. (J13.63.w1)

Erinaceus europaeus - West European Hedgehog:

  • 4 mg/kg by subcutaneous injection, once daily for three days. (J15.21.w1)
  • 5-10 mg/kg once daily or twice daily, subcutaneous or oral. For analgesia and reducing inflammation; use generally restricted to three days of treatment. (B284.6.w6)
  • 5mg/kg subcutaneously once daily. (D93)
  • 4 mg/kg subcutaneously at 24-36 hour intervals. (D107)

Bears (Ursidae - Bears (Family)):

  • For analgesia: 3.2 mg/kg subcutaneously as soon as the bear has been anaesthetised (for Cholecystectomy in Bears) and post-operatively 4.4 mg/kg orally once daily. (V.w89, V.w90)
  • Has been used long-term by Animals Asia Foundation in some bears with severe arthritis, at 4.4 mg/kg orally daily, with apparent minimal untoward effect on the liver (no significant rise in liver enzymes after a year of daily treatment). (V.w90)

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

  • 1.5 mg/kg orally twice daily. (B373.Guide.w41)
  • 2.0 - 4.0 mg/kg subcutaneously once daily. (B373.Guide.w41)
  • 2.0 - 4.0 mg/kg subcutaneously once daily. (B600.4.w4, B601.15.w15)
  • 1.5 mg/kg orally twice daily. (Mix tablets with jam, fruit juice or syrup). (B600.4.w4)
  • 1.0 - 2.0 mg/kg orally every 12 hours. (B602.41.w41)
  • 2.0 - 4.0 mg/kg orally or subcutaneously every 24 hours. (B603.5.w5)
  • 1.5 mg/kg orally or 1 - 2 mg/kg subcutaneously or intravenously, every 24 hours. (B546)
  • 1.0 - 2.2 mg/kg orally every 12 hours. (B548.w8)
  • 1.5 mg/kg orally every 12 hours. (B548.w8)
  • 2.2 mg/kg orally every 12 hours. (B548.w8)
  • 2.0 - 4.0 mg/kg subcutaneously every 24 hours. (B548.w8)
  • 4.0 mg/kg subcutaneously or intramuscularly every 24 hours. (B548.w8)

Ferrets - Mustela putorius furo - Ferret:

  • 1 mg/kg orally every 12 - 24 hours. (B602.41.w41)
  • (B626.App.w22)
  • (B631.21.w21)

Great Apes

Monitoring parameters
  • Monitor if on long-term treatment. (B201.10.w10)
  • Prior to administration, particularly in geriatric dogs, those with chronic pre-existing disease and those in which prolonged treatment is likely, baseline data should be established (physical examination, haematology, biochemistry, urinalysis). (B263)
  • Liver enzyme levels should be reassessed after one week of treatment, discontinuing therapy if these are raised from baselines, and for individuals on prolonged therapy, at intervals. (B263)
  • Clinical efficacy should be monitored. (B263)
  • Monitor for signs of adverse effects e.g. inappetance, diarrhoea, vomiting, melaena, polyuria/polydipsia, anaemia, jaundice, lethargy, behavioural changes, ataxia, seizures. (B263)

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Withdrawal period / Withholding time
Notes Eire:
  • "Slaughter 21 days; should not be used in cattle producing milk for human consumption." Data for Rimadyl Injection (Pfizer, Eire) and Zenecarp Solution (Cypharm, Eire) following subcutaneous or intravenous injection. (B201.10.w10)

UK: 

  • "Cattle must not be slaughtered for human consumption during treatment or within 21 days of treatment with Rimadyl Large Animal Solution". (B266)
  • "Not for use in cattle producing milk for human consumption." (B266)

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Contraindicated in individuals with a history of hypersensitivity to this drug or to other propionic-class NSAIDs. (B201.10.w10, B263)
  • Contraindicated in dogs with bleeding disorders such as Von Willebrand's disease. (B263)
  • Use with caution in individuals with pre-existing chronic disease such as inflammatory bowel disease, renal insufficiency or hepatic insufficiency. (B263)
  • Contraindicated in individuals with cardiac, renal or hepatic disease. (B201.10.w10)
  • Contraindicated in individuals in which there is a possibility of gastro-intestinal ulceration or bleeding. (B201.10.w10)
  • Contraindicated as a treatment concurrent with (or within 24 hours of) other NSAIDs. (B201.10.w10)
  • Horses: Contraindicated in racehorses prior to racing. (B201.10.w10)
  • Contraindicated in pregnant animals. (B340.10.w10); contraindicated in pregnant horses. (B201.10.w10)
  • Use with caution in pregnancy (may not have been fully evaluated for safety). (B201.10.w10)
  • Use with caution in animals less than six weeks old, aged animals, individuals with dehydration, hypovolaemia or hypotension. (B340.10.w10, B201.10.w10)
  • Avoid using concurrently with, or within 24 hours of, use of other NSAIDs. (B340.10.w10, B201.10.w10)
  • Avoid using concurrently with potentially nephrotoxic drugs. (B340.10.w10, B201.10.w10)
  • Not recommended for concomitant administration with aspirin (see drug interactions above). (B263)
  • Rabbits: Use with care in hypotensive individuals. (B600.4.w4)
Adverse Effects / Side Effects / Warnings
  • Adverse effects are uncommon. (B263)
  • Mild gastro-intestinal effects are the most likely side-effects. (B263)
  • With prolonged use, possibility of gastro-intestinal lesions, inappetance, vomiting, diarrhoea. (B201.10.w10)
  • Serious effects which have been reported include hepatocellular damage and/or renal disease, haematological effects and gastro-intestinal effects. (B263)
  • Side effects (toxicity) may be more likely to occur in elderly dogs or those with chronic diseases such as inflammatory bowel disease, renal insufficiency or hepatic insufficiency. (B263)
  • One third of cases of reported hepatic syndrome were in Labrador Retrievers, although this was not proven to be statistically significant. (B263)
  • Use with care in very young (less than six weeks old) or old animals. (B201.10.w10)
  • Avoid using in individuals with dehydration, hypovolaemia or hypotension. (B201.10.w10)
  • Avoid using concurrently with potentially nephrotoxic drugs. (B201.10.w10)
Operator Warnings --
Overdose / Acute Toxicity
  • May be significant variations between individuals in responses to either acute or chronic overdose. (B263)

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Detailed Toxicological Information
Classification --
Acute Toxicity
  • Dogs: little adverse reaction reported following studies with repeated doses of up to ten times recommended dose. Effects seen included hypoalbuminaemia, melaena, slight ALT increase. (B263)
Chronic Toxicity Bears (Ursidae - Bears (Family)):
  • Note: has been used long-term by Animals Asia Foundation in some bears with severe arthritis with apparent minimal untoward effect on the liver (no significant rise in liver enzymes after a year of daily treatment at 4.4 mg/kg orally. (V.w90)
Reproductive effects
  • In rats: little evidence of teratogenicity following administration to rats at 2 mg/kg, 6mg/kg or 20 mg/kg. Slightly prolonged gestation and a small increase in fetal deaths was observed with the highest dose. (J289.27S1.w1)
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

--

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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