Flunixin Injection (Canada)

Company: Zoetis

Flunixin 50 mg/mL (as meglumine USP)

Veterinary Use Only

Sterile Injectable Solution

Anti inflammatory / Analgesic / Antipyretic

DIN: 02234061

50 mg/mL flunixin (equivalent to 83 mg flunixin meglumine USP).

For intravenous or intramuscular use in horses and for intravenous use only in cattle

Pharmacological Classification

Anti-inflammatory; analgesic; antipyretic.

Structural Formula And Chemistry

Flunixin meglumine is the N-methyl-glucamine salt of (2 (2’-methyl-3’-trifluoromethyl-anilino) nicotinic acid).

Molecular Formula: C₁₄H₁₁F₃N₂O₂•C₇H₁₇NO₅

Molecular Weight: 491.46

Description

Each milliliter of Flunixin Injection contains: Active ingredient: 50 mg flunixin equivalent to 83 mg flunixin meglumine USP; non medicinal ingredients: 0.1 mg edetate disodium, 2.5 mg sodium formaldehyde sulfoxylate, 4.0 mg diethanolamine, 207.2 mg propylene glycol, 5.0 mg phenol as preservative, hydrochloric acid to adjust the pH, water for injection q.s.

Flunixin Injection Indications

Horses: Flunixin Injection is recommended for the alleviation of inflammation and associated pain in musculoskeletal disorders in the horse. Flunixin Injection is also recommended for the alleviation of visceral pain associated with colic in the horse.

Cattle: Flunixin Injection is indicated for the control of pyrexia associated with Bovine Respiratory Disease (BRD), endotoxemia and acute bovine mastitis. Flunixin Injection is also indicated for the control of inflammation associated with endotoxemia. In clinical studies, flunixin as an adjunct to antibiotic therapy with oxytetracycline has been demonstrated to control pyrexia associated with bovine respiratory disease.

Pharmacology

Flunixin meglumine is a potent, non-narcotic, non-steroidal, analgesic agent with anti-inflammatory activity. Antipyretic activity has been demonstrated in cattle and laboratory animals. It is significantly more potent than pentazocine, meperidine and codeine as an analgesic in the rat yeast paw test.

Horse: Flunixin is four times as potent on a mg per mg basis as phenylbutazone as measured by the reduction in lameness and swelling in the horse. Plasma half-life in horse serum is 1.6 hours following a single dose of 1.1 mg flunixin per kg. Measurable amounts are detectable in horse plasma at 8 hours post injection.

Cattle: Flunixin meglumine is a weak acid (pKa = 5.82) which exhibits a high degree of plasma protein binding (app. 99%). However, free (unbound) drug appears to readily partition into body tissues (V_ss predictions range from 297 to 782 mL/kg). Total body water is approximately 570 mL/kg. In cattle, elimination occurs primarily through biliary excretion. This may, at least in part, explain the presence of multiple peaks in the blood concentration/time profile following IV administration.

In healthy cattle, a total body clearance has been reported to range from 90 to 150 mL/kg/hr. These studies also report a large discrepancy between the volume of distribution at steady state (V_ss) and the volume of distribution associated with the terminal elimination phase (V_β). This discrepancy appears to be attributable to extended drug elimination from a deep compartment. The terminal half-life has been shown to vary from 3.14 to 8.12 hours.

Model and field studies have shown that flunixin can have short-term effect in the control of some inflammatory factors associated with endotoxemia and irritation (carregeenan).

Flunixin persists in inflammatory tissues and is associated with anti-inflammatory properties which extend well beyond the period associated with detectable plasma drug concentrations. These observations account for the counterclockwise hysteresis associated with flunixin’s pharmacokinetic/pharmacodynamic relationship. Therefore, prediction of drug concentrations based upon the estimated plasma terminal half-life will likely underestimate both the duration of drug action and the concentration of drug remaining at the site of activity.

Flunixin Injection Dosage And Administration

Horses: The recommended dose for musculoskeletal disorders is 1.1 mg flunixin per kg (1 mL/45 kg) of body weight once daily. Treatment may be given by intravenous or intramuscular injection and repeated for up to 5 days. Intravenous studies show that the onset of activity is within 2 hours. Peak response occurs between 12 and 16 hours and duration of activity is 24 to 36 hours following intravenous and intramuscular administration.

The recommended dose for the alleviation of pain associated with equine colic is 1.1 mg flunixin per kg of body weight. Intravenous administration is recommended for prompt relief. Should colic symptoms recur, treatment may be repeated as necessary. Clinical studies show that pain symptoms were alleviated in 37% of treated horses within 15 minutes, and 74% within 30 minutes. The cause of colic should be determined and treated with concomitant therapy.

Cattle: The recommended dose for control of pyrexia associated with bovine respiratory disease and endotoxemia and control of inflammation associated with endotoxemia in cattle is 2.2 mg flunixin per kg (2 mL/45 kg) of body weight given by slow intravenous administration once a day for up to 3 days. The total daily dose should not exceed 2.2 mg flunixin per kg of body weight. Avoid rapid intravenous administration of the drug. Twenty-four (24) hours after administration, check if animal is febrile. Re-administer only if the fever is 104°F (40°C) or higher. The recommended dose for control of pyrexia associated with acute bovine mastitis is 2.2 mg flunixin per kg of body weight given as a single intravenous injection. Administer slowly.

Contra-indications

Horses: Do not administer intra-arterially. Inadvertent intra-arterial injection may cause adverse reactions. Signs can be ataxia, incoordination, hyperventilation, hysteria and muscle weakness. Signs are transient and disappear without antidotal medication within a few minutes. Do not use in horses showing hypersensitivity to flunixin meglumine.

Cattle: Do not administer intra-arterially. Inadvertent intra-arterial injection may cause adverse reactions. Do not use in cattle showing hypersensitivity to flunixin meglumine. The drug is contraindicated in animals with hepatic disease, renal and cardiovascular impairment, gastrointestinal ulceration and/or platelet disorders. It is also contraindicated in dehydrated animals.

Flunixin Injection Cautions

The use of NSAIDS may be associated with gastrointestinal, hepatic or renal toxicity. Patients at greatest risk for renal toxicity are those that are dehydrated, on concomitant diuretic therapy or those with renal, cardiovascular, and/or hepatic dysfunctions. Concurrent administration of potentially nephrotoxic drugs should be carefully approached. NSAIDs may inhibit prostaglandins that maintain normal homeostatic function. Such prostaglandin effects may result in clinically significant disease in patients with underlying or pre-existing disease that has not been previously diagnosed. Due to the potential for NSAIDs to induce gastrointestinal ulceration, concomitant use of this drug with other anti-inflammatory drugs, such as other NSAIDs or corticosteroids should be avoided. With the exception of the antibiotic oxytetracycline in cattle, studies to determine the activity of flunixin when administered concomitantly with other drugs have not been conducted. Drug compatibility should be monitored closely in patients requiring adjunctive therapy. Discontinue use if hematuria or fecal blood are observed. Avoid rapid intravenous administration of the drug.

Horses: The effect of flunixin on reproduction in horses has not been determined. Studies using flunixin in rats and rabbits showed no teratogenicity.

Cattle: Do not use in bulls intended for breeding as reproductive effects of Flunixin Injection in this class of cattle have not been investigated. NSAIDs are known to have potential effects on both parturition and the estrous cycle. There may be a delay in the onset of estrus if flunixin is administered during the prostaglandin phase of the estrous cycle. The effects of flunixin on imminent parturition have not been evaluated in a controlled study. NSAIDs are known to have the potential to delay parturition through a tocolytic effect. Do not exceed the recommended dose.

Adverse Reactions

During clinical studies no significant side effects were reported when the drug was injected slowly. In cattle, a temporary head thrashing can occur if the drug is injected too rapidly.

Toxicity

No toxic effects were observed in rats given intramuscular flunixin 4 mg flunixin per kg per day for 28 days. No adverse effects were seen in dogs given a single intramuscular injection of 50 mg flunixin per kg. Higher doses resulted in salivation, panting, emesis and tremors. No toxic effects were observed in monkeys given intramuscular doses between 3 and 30 mg flunixin per kg per day for 28 days. Horse: Prolonged parenteral treatment in horses at 4.4 mg flunixin per kg body weight showed no untoward effects. Cattle: No flunixin-related changes (adverse reactions) were noted in cattle administered a 1X (2.2 mg flunixin per kg) dose for 9 days (three times the maximum clinical duration). Toxicity, such as blood in feces and/or urine, manifested itself at moderately elevated doses (3X and 5X) when flunixin was administered daily for 9 days (three times the maximum recommended duration for bovine respiratory disease and endotoxemia and nine times the maximum recommended duration for acute bovine mastitis).

Warnings

Treated cattle must not be slaughtered for use in food for at least 6 days after the latest treatment with this drug. Milk taken from treated animals during treatment and within 36 hours after the latest treatment with this drug must not be used in food. Do not use in dry dairy cows. Do not use in veal calves as a withdrawal period has not been established in pre-ruminating calves. Do not use in horses that are to be slaughtered for food. KEEP OUT OF REACH OF CHILDREN.

Storage

Store below 25°C.

How Supplied

Flunixin Injectable, 50 mg flunixin/mL (equivalent to 83 mg flunixin meglumine/mL) is available in 100 mL and 250 mL multidose vials.

Manufactured by:

Norbrook Laboratories Limited, Newry, Northern Ireland BT35 6PU

Distributed by:

Zoetis Canada Inc., Kirkland QC H9H 4M7

CPN.: 1198372.5