Banamine Sterile Solution Injectable (Canada)

Manufacturer: Schering-Plough

DIN 00465305

Veterinary Use Only

50 Mg/ml Flunixin (equivalent To 83 Mg Flunixin Meglumine Usp).

For Intravenous Or Intramuscular Use In Horses, For Intravenous Use Only In Cattle And For Intramuscular Use Only In Swine.

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 BANAMINE Solution Injectable 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 and water for injection q.s.

Banamine Sterile Solution Injectable Indications

Horses

BANAMINE Solution Injectable is recommended for the alleviation of inflammation and associated pain in musculoskeletal disorders in the horse. BANAMINE Solution Injectable is also recommended for the alleviation of visceral pain associated with colic in the horse.

Cattle

BANAMINE Solution Injectable is indicated for the control of pyrexia associated with Bovine Respiratory Disease (BRD), endotoxemia and acute bovine mastitis. BANAMINE is also indicated for the control of inflammation associated with endotoxemia. BANAMINE Solution Injectable used as an adjunct to antibiotic therapy with oxytetracycline has been demonstrated to control pyrexia associated with bovine respiratory disease.

Swine

BANAMINE Injectable Solution is indicated as an aid in reducing pyrexia associated with swine 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 in 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, 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.

Swine

The pharmacokinetic profiles were found to follow a 2-compartmental model, although a deep (third) compartment was observed in some animals. The mean terminal elimination half-life (β half-life) of flunixin after a single intramuscular injection of Banamine (2.2 mg flunixin per kg) to pigs was between 3 and 4 hours. The mean observed maximum plasma concentration was 2944 ng/mL, achieved at a mean time of approximately 0.4 hours. The mean AUC_(0-LOQ) was 6431 ng•hr/mL. Following IM administration of flunixin, quantifiable drug concentration could be measured up to 18 hours post dose. The mean volume of distribution was 2003 mL/kg and the mean total clearance was 390 mL/hr/kg. The mean absolute bioavailability of flunixin following an intramuscular injection in the neck was 87%.

Banamine Sterile Solution Injectable 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.

Swine

The recommended dose for swine is 2.2 mg flunixin per kg (2 mL per 45 kg) body weight given by a single intramuscular administration. The injection should be given only in the neck musculature with a maximum of 10 mL per site.

Contraindications

Horse

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, gastro-intestinal ulceration and/or platelet disorders. It is also contra-indicated in dehydrated animals.

Swine

Do not use in animals showing hypersensitivity to flunixin meglumine. Use judiciously when renal impairment or gastric ulceration is suspected. Not for use in breeding swine. The reproductive effects of BANAMINE Solution Injectable have not been investigated in this class of swine.

Banamine Sterile Solution Injectable Caution

The use of NSAIDS may be associated with gastro-intestinal, hepatic and 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 the 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 gastro-intestinal ulceration, concomitant use of this drug with other anti-inflammatory drugs, such as other NSAIDs and corticosteroids should be avoided. With the exception of the antibiotic oxytetracycline in cattle and swine, studies to determine the activity of BANAMINE when administered concomitantly with other drugs have not been conducted. Drug compatibility should be monitored closely.

Discontinue use if hematuria or fecal blood are observed. Avoid rapid intravenous administration of the drug.

Horses

The effect of BANAMINE on reproduction in horses has not been determined. Studies on reproduction in rats and rabbits have shown no teratogenicity.

Cattle

Do not use in bulls intended for breeding as reproductive effects of BANAMINE 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.

Side Effects

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. In swine, flunixin was mildly irritating at the injection sites. No other flunixin-related changes (adverse reactions) were noted in swine administered at IX (2.2 mg flunixin per kg) dose for 9 days. Minimal toxicity manifested itself as statistically significant increased spleen weight at elevated doses (5X or higher daily for 9 days) with no change in normal microscopic architecture.

Toxicity

No toxic effects were observed in rats given intramuscular flunixin 4 mg/kg/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 recommended 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).

Warning

Treated animals must not be slaughtered for use in food for at least, 6 days for cattle and 13 days for swine, after the latest treatment with this drug. Milk taken from treated animals within 36 hours after the latest treatment must not be used in food. Not for use in dry dairy cows or in veal calves. This drug is not to be administered to horses that are to be slaughtered for food. Keep out of reach of children.

Note: in swine, intramuscular injection may cause local tissue irritation and damage. In an injection-site irritation study, the tissue damage did not resolve in all animals by Day 28 post-injection. This may result in trim loss of edible tissue at slaughter.

Storage

Store between 2° and 30° C (36° and 86° F).

How Supplied

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

^® Registered trademark of Schering-Plough Canada Inc.

SCHERING-PLOUGH CANADA INC., Kirkland, Québec H9H 4M7

Nac No.

12080098