FLUNIX

flunixantiinflammatory injection

ACTIVE CONSTITUENT:

FLUNIXIN (as meglumine) 50 mg/mL

Non-steroidal antiinflammatory, analgesic and antipyretic

for use in horses, cattle, pigs and dogs.

50mL/100mL

PHARMACOLOGY:

Actions

Flunixin meglumine is a non-steroidal antiinflammatory agent with analgesic and antipyretic activity. Flunixin, through inhibition of cyclooxygenase, blocks synthesis of eicosanoids, including prostaglandins, thromboxane, and prostacyclin (PGI2), which are chemical mediators of inflammation. Of the NSAIDs, flunixin is considered to be the most potent cyclooxygenase inhibitor. In contrast to other NSAIDs, therapeutic pharmacological effects are associated with relatively low plasma levels of flunixin. It is reported to be a more potent analgesic than meclofenamic acid, phenylbutazone, naproxen, salicylic acid, pentazocine lactate, pethidine hydrochloride, and codeine phosphate, and to provide comparable analgesia to clinically effective doses of morphine. Analgesic and antiinflammatory effects of flunixin are dose-related and tolerance, as occurs with narcotic agents, apparently does not develop to the action of flunixin.

Clinical studies have confirmed the analgesic and antiinflammatory efficacy of flunixin in the therapy of musculoskeletal disorders in horses and dogs, and of colic in horses. In equine colic models flunixin analgesia has been found superior to that of pethidine. Flunixin does not significantly alter gastrointestinal motility, blood pressure, or cardiac rhythm in horses. Thromboxane and prostacyclin are involved in the adverse haemodynamic changes associated with endotoxic shock. Flunixin administration decreases endotoxin-induced lactic acidosis, reduces severity of arterial hypotension and endothelial cell injury, and improves venous return. Flunixin treatment of dogs with experimental E. coli septicaemia prevents arterial hypotension and hypoxaemia and has resulted in improved animal survival.

Vascular changes in uveitis may be mediated at least in part by endogenous prostaglandin release, and a cause and effect relationship between prostaglandin release and subsequent increase in aqueous protein concentration has been established. Administration of flunixin prior to intraocular surgery is effective in reducing aqueous humour prostacyclin accumulation in the horse. Intravenous flunixin, alone or in combination with a corticosteroid, has been shown to reduce aqueous flare in dogs after intraocular surgery.

Pharmacokinetics

Flunixin has a rapid onset and long duration of action. Therapeutic effects are manifest within 2 hours after parenteral or oral administration. Peak response is reached between 12 and 16 hours after administration, and duration of action is up to 36 hours. The plasma half-life is reported to be 1.6 hours in horses, 3.7 hours in dogs, and 8.1 hours in cattle. Flunixin is widely distributed throughout body tissues and fluids. Renal excretion is significant in the elimination of flunixin, which is excreted in the urine largely in conjugated form. Excretion via bile and other gastrointestinal secretions may also occur. Flunixin is detectable, by conventional analytical methods, in equine urine for at least 72 hours after dosing and may be detectable by some techniques for up to 15 days after administration. Drug clearance time after sequential doses does not differ significantly from that following a single dose.

Flunixin apparently does not accumulate in body tissues. NSAIDs however, being acidic, have a propensity to accumulate at sites of low pH such as at regions of inflammation. In experimental models of acute inflammation in horses, concentrations of flunixin in inflammatory exudate have been found to be higher than those in plasma by 6 hours after intravenous administration of a single therapeutic dose. Flunixin suppresses the production of PGE2 in inflammatory exudates for 12 to 24 hours after a single intravenous dose. The long pharmacological action of flunixin is at variance with its short plasma half-life in the horse. This may be attributable to the capacity of NSAIDs to irreversibly bind to cyclooxygenase, the accumulation of flunixin at inflammatory sites, and the prolonged excretion of the agent from the body.

CLINICAL APPLICATION

Flunix provides effective antiinflammatory and analgesic action in a wide range of musculoskeletal disorders in horses, dogs, cattle and pigs. In those species it may be used in the therapy of arthritis, myositis, and traumatic injuries resulting in fractures and contusions. Flunix administration results in effective visceral analgesia in cases of equine colic due to flatulence or inflammatory causes. Flunixin is considered to be a more potent analgesic than many of the narcotic or other non-steroidal anti-inflammatory drugs and is widely used in the therapy of equine colic. Flunixin, when used in the therapy of equine colic, may mask the behavioral and cardiopulmonary signs associated with endotoxaemia or intestinal devitalisation. Intravenous administration of flunixin has been advocated in the therapy of ocular inflammatory conditions, and may be employed pre- and post-operatively to reduce inflammation resulting from intraocular surgery in the horse and dog. Flunix may be a useful alternative, or adjunct, to corticosteroids in such cases. Flunixin may be administered subconjunctivally prior to intraocular surgery in the horse to reduce aqueous humour prostacyclin accumulation. Flunix has been used successfully to reduce the adverse haemodynamic changes which characterize endotoxic shock in both horses and dogs. The agent is also recommended as an adjunct to the therapy of Mastitis-Metritis-Agalactia (MMA) syndrome in sows. Therapeutic effects in such cases are observed at, or below, antiinflammatory dose rates of flunixin.

In cattle, Flunix is used for its antiinflammatory and analgesic actions in the therapy of aseptic laminitis and peripheral nerve injury resulting from direct trauma or pressure. Flunixin administered intravenously at 1.1 mg/kg daily has also been recommended as an adjunct to the treatment of persistent hyperthermia. Flunix may be administered either intravenously or intramuscularly with comparable efficacy, and onset and duration of action. Flunixin has a long pharmacological action, and therapeutic effects are maintained even at low plasma concentrations. Care should be taken to avoid intra-arterial injection of flunixin as it may cause transient CNS stimulation, ataxia, hyperventilation, and muscle weakness. Flunixin has a wide margin of safety and reports of adverse reactions are rare at therapeutic dose rates and recommended treatment durations. Intravenous administration of flunixin at up to five times the recommended dose rate and for twice the recommended treatment period have been reported to produce no gross clinical abnormalities and no changes in haematological, biochemical or urinary parameters. Parenteral administration of the agent rarely causes tissue irritation; it may be slightly irritant when administered by intramuscular injection to young animals or if injected too superficially into older animals.

Safety of the use of flunixin during pregnancy has not been established.

DIRECTIONS FOR USE:

Do not use in cats.
Do not admix in syringe with other compounds.
Do not use concomitantly with other anti-inflammatory drugs, or with nephrotoxic substances.
Use with caution in animals with preexisting gastrointestinal ulceration, renal, hepatic or haematologic disorders.

Horses: 1.1 mg/kg (1 mL/45 kg) bodyweight daily for up to 5 days, by intravenous or intramuscular injection.

Cattle: 1.1 – 2.2 mg/kg (1 – 2 mL/45 kg) bodyweight daily for 3 to 5 days, by intravenous or intramuscular injection.

Pigs: 1.1 – 2.2 mg/kg (1 – 2 mL/45 kg) bodyweight daily for up to 3 days, by deep intramuscular injection.

Dogs: 1 mg/kg (0.2 mL/10 kg) bodyweight daily for up to 3 days, by intravenous or intramuscular injection.

As with other NSAIDs, flunixin should be used cautiously in conjunction with highly protein-bound drugs such as phenytoin, valproic acid, oral anticoagulants, other anti-inflammatory agents, and sulfonamides. Prostaglandins have a cytoprotective action on the gastric mucosa, and in some species maintenance of renal blood flow in hypovolaemic states is prostaglandin dependent. Flunixin should therefore be used with caution in conjunction with ulcerogenic or nephrotoxic agents, in cases of pre-existing gastrointestinal ulceration or renal disease, and in hypovolaemic patients. Care should be exercised in the use of flunixin in patients with hepatic disease, haematological disorders or severe cardiac failure.

WITHHOLDING PERIODS:

CATTLE: MEAT: DO NOT USE LESS than 28 days before slaughter for human consumption.

MILK: Milk collected from cows within 36 hours following treatment MUST NOT BE USED for human consumption or processing. This milk should not be fed to bobby calves.

PIGS: DO NOT USE LESS than 28 days before slaughter for human consumption.

HORSES: Meat withholding period 28 days.

ADVERSE EFFECTS:

Occasional cases of localised swelling, induration, muscle stiffness, and sweating have been reported following intramuscular injection of flunixin in horses. A case of flunixin toxicity has been reported in a pony mare after intravenous administration of flunixin at greater than 5 times the recommended dose for 5 days. Clinical signs observed included anorexia, depression, gastrointestinal ulceration, hypoproteinaemia and neutropaenia. In dogs treated with flunixin at excessive doses or for prolonged periods, vomiting, diarrhoea, and gastrointestinal ulceration may occur.

DISPOSAL:

Dispose of empty container by wrapping with paper and putting in garbage

STORAGE:

Store below 30°C (Room Temperature).

[50mL:] APVMA Approval No. 47802/50mL/0104

[100mL:] APVMA Approval No. 47802/100mL/0104

PARNELL LABORATORIES (AUST) PTY. LTD.

6/476 Gardeners Road, Alexandria, NSW 2015

[50ML]: R236-03

[100ML]: R718-01