Banamine

Schering Corporation

Banamine (FLUNIXIN MEGLUMINE)

FULL PRESCRIBING INFORMATION: CONTENTS*

• CAUTION
• BANAMINE DESCRIPTION
• PHARMACOLOGY
  • Horse
  • Cattle
• INDICATIONS
  • Horse
  • Cattle
• DOSE AND ADMINISTRATION
  • Horse
  • Cattle
• BANAMINE CONTRAINDICATIONS
  • Horse
  • Cattle
• PRECAUTIONS
  • Horse
  • Cattle
• SAFETY
  • Horse
  • Cattle
• BANAMINE ADVERSE REACTIONS
• HOW SUPPLIED
• REFERENCES
• PRINCIPAL DISPLAY PANEL - 100 mL Multiple-Dose Vial 50 mg/mL Carton

FULL PRESCRIBING INFORMATION

Injectable Solution
50 mg/mL
Veterinary

Only for Intravenous Use in Beef and Dairy Cattle.
Not for Use in Dry Dairy Cows and Veal Calves.
For Intravenous and Intramuscular Use in Horses.

PRODUCT INFORMATION

NADA #101-479, Approved by FDA.

CAUTION

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

BANAMINE DESCRIPTION

Each milliliter of BANAMINE Injectable Solution contains flunixin meglumine equivalent to 50 mg flunixin, 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, water for injection qs.

PHARMACOLOGY

Flunixin meglumine is a potent, non-narcotic, nonsteroidal, analgesic agent with anti-inflammatory and antipyretic activity. 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/kg. Measurable amounts are detectable in horse plasma at 8 hours postinjection.

Cattle

Flunixin meglumine is a weak acid (pKa=5.82)¹ which exhibits a high degree of plasma protein binding (approximately 99%).² However, free (unbound) drug appears to readily partition into body tissues (V_ss predictions range from 297 to 782 mL/kg.^2-5 Total body water is approximately equal to 570 mL/kg).⁶ In cattle, elimination occurs primarily through biliary excretion.⁷ This may, at least in part, explain the presence of multiple peaks in the blood concentration/time profile following IV administration.²

In healthy cattle, total body clearance has been reported to range from 90 to 151 mL/kg/hr.^2-5 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.⁸ The terminal half-life has been shown to vary from 3.14 to 8.12 hours.^2-5

Flunixin persists in inflammatory tissues⁹ and is associated with anti-inflammatory properties which extend well beyond the period associated with detectable plasma drug concentrations.^4,9 These observations account for the counterclockwise hysteresis associated with flunixin's pharmacokinetic/pharmacodynamic relationships.¹⁰

Therefore, prediction of drug concentrations based upon the estimated plasma terminal elimination half-life will likely underestimate both the duration of drug action and the concentration of drug remaining at the site of activity.

INDICATIONS

Horse

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

Cattle

BANAMINE Injectable Solution is indicated for the control of pyrexia associated with bovine respiratory disease, endotoxemia and acute bovine mastitis. BANAMINE Injectable Solution is also indicated for the control of inflammation in endotoxemia.

DOSE AND ADMINISTRATION

Horse

The recommended dose for musculoskeletal disorders is 0.5 mg per pound (1 mL/100 lbs) of body weight once daily. Treatment may be given by intravenous or intramuscular injection and repeated for up to 5 days. Studies show onset of activity is within 2 hours. Peak response occurs between 12 and 16 hours and duration of activity is 24-36 hours.

The recommended dose for the alleviation of pain associated with equine colic is 0.5 mg per pound of body weight. Intravenous administration is recommended for prompt relief. Clinical studies ,how pain is alleviated in less than 15 minutes in many cases. Treatment may be repeated when signs of colic recur. During clinical studies approximately 10% of the horses required one or two additional treatments. 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 in endotoxemia, is 1.1 to 2.2 mg/kg (0.5 to 1 mg/lb; 1 to 2 mL per 100 lbs) of body weight given by slow intravenous administration either once a day as a single dose or divided into two doses administered at 12-hour intervals for up to 3 days. The total daily dose should not exceed 2.2 mg/kg (1.0 mg/lb) of body weight. Avoid rapid intravenous administration of the drug.

The recommended dose for acute bovine mastitis is 2.2 mg/kg (1mg/lb;2 ml per 100lbs) of body weight given once by intravenous administration.

BANAMINE CONTRAINDICATIONS

Horse

There are no known contraindications to this drug when used as directed. Intra-arterial injection should be avoided. Horses inadvertently injected intra-arterially can show 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

There are no known contraindications to this drug in cattle when used as directed. Do not use in animals showing hypersensitivity to flunixin meglumine. Use judiciously when renal impairment or gastric ulceration are suspected. NSAIDs inhibit production of prostaglandins which are important in signaling the initiation of parturition. The use of flunixin can delay parturition and prolong labor. Do not use Banamine Injectable Solution within 48 hours of expected parturition.

PRECAUTIONS

As a class, cyclo-oxygenase inhibitory NSAIDs may be associated with gastrointestinal and renal toxicity. Sensitivity to drug-associated adverse effects varies with the individual patient. Patients at greatest risk for renal toxicity are those that are dehydrated, on concomitant diuretic therapy, or those with renal, cardiovascular, and/or hepatic dysfunction.

Since many NSAIDs possess the potential to induce gastrointestinal ulceration, concomitant use of BANAMINE Injectable Solution with other anti-inflammatory drugs, such as other NSAIDs and corticosteroids, should be avoided or closely monitored.

Horse

The effect of BANAMINE Injectable Solution on pregnancy has not been determined. Studies to determine activity of BANAMINE Injectable Solution when administered concomitantly with other drugs have not been conducted. Drug compatibility should be monitored closely in patients requiring adjunctive therapy.

Cattle

Do not use in bulls intended for breeding, as reproductive effects of Banamine Injectable Solution in these classes of cattle have not be investigated. NSAIDs are known to have potential effects on both parturition (See Contraindications) 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. NSAIDs are known to have the potential to delay parturition through a tocolytic effect. The use of NSAIDs in the immediate post-partum period may interfere with uterine involution and expulsion of fetal membranes. Cows should be monitored carefully for placental retention if Banamine Injectable Solution is used within 24 hours after parturition.

SAFETY

Horse

A 3-fold intramuscular dose of 1.5 mg/lb of body weight daily for 10 consecutive days was safe. No changes were observed in hematology, serum chemistry, or urinalysis values. Intravenous dosages of 0.5 mg/lb daily for 15 days; 1.5 mg/lb daily for 10 days; and 2.5 mg/lb daily for 5 days produced no changes in blood or urine parameters. No injection site irritation was observed following intramuscular injection of the 0.5 mg/lb recommended dose. Some irritation was observed following a 3-fold dose administered intramuscularly.

Cattle

No flunixin-related changes (adverse reactions) were noted in cattle administered a 1× (2.2 mg/kg; 1.0 mg/lb) dose for 9 days (three times the maximum clinical duration). Minimal toxicity manifested itself at moderately elevated doses (3× and 5×) when flunixin was administered daily for 9 days, with occasional findings of blood in the feces and/or urine. Discontinue use if hematuria or fecal blood are observed.

BANAMINE ADVERSE REACTIONS

In horses, isolated reports of local reactions following intramuscular injection, particularly in the neck, have been received. These include localized swelling, sweating, induration, and stiffness. In rare instances in horses, fatal or nonfatal clostridial infections or other infections have been reported in association with intramuscular use of BANAMINE Injectable Solution. In horses and cattle, rare instances of anaphylactic-like reactions, some of which have been fatal, have been reported, primarily following intravenous use.

HOW SUPPLIED

BANAMINE Injectable Solution, 50 mg/ mL, is available in 100-mL (NDC 0061-0851-03), and 250-mL (NDC 0061-0851-04) multi-dose vials.

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

REFERENCES

• Johansson M, Anler EL. Gas chromatographic analysis of flunixin in equine urine after extractive methylation. J Chromatogr. 1988;427:55-66.
• Odensvik K, Johansson M. High-performance liquid chromatography method for determination of flunixin in bovine plasma and pharmacokinetics after single and repeated doses of the drug. Am J Vet Res. 1995; 56:489-495.
• Anderson KL, Neff-Davis CA, Davis LE, Bass VD. Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations. Am J Vet Res. 1990;51:1464-1467.
• Odensvik K. Pharmacokinetics of flunixin and its effect on prostaglandin F_2α metabolite concentrations after oral and intravenous administration in heifers. J Vet Pharmacol Ther. 1995;18:254-259.
• Hardee GE, Smith JA, Harris SJ. Pharmacokinetics of flunixin meglumine in the cow. Res Vet Sci. 1985;39:110-112.
• Ruckebusch Y, Phaneuf LP, Dunlop R. Physiology of Small and Large Animals. Chapter 2: "Body Fluid Compartments," Philadelphia, Pa: B.C. Decker; 1991:8-18.
• Kopcha M, Ahl AS. Experimental uses of flunixin meglumine and phenylbutazone in food-producing animals. J Am Vet Med Assoc. 1989;194:45-49.
• Wagner JG. Significance of ratios of different volumes of distribution in pharmacokinetics. Biopharm & Drug Dispos.1983;4:263-270.
• Lees P, Higgins AJ. Flunixin inhibits prostaglandin E₂ production in equine inflammation. Res Vet Sci.1984;37:347-349.
• Landoni MF, Cunningham FM, Lees P. Determination of pharmacokinetics and pharmacodynamics of flunixin in calves by use of pharmacokinetic/pharmacodynamic modeling. Am J Vet Res. 1995;56:786-794.

May 2011

Banamine is the property of Intervet International B.V. or affiliated companies or licensors and is protected by copyrights, trademark and other intellectual property laws.

Copyright © 1985, 2011 Intervet International B.V.
All rights reserved.

Made in Germany

116978 R2 R
116978 R2 V

Intervet
Schering-Plough Animal Health

PRINCIPAL DISPLAY PANEL - 100 mL Multiple-Dose Vial 50 mg/mL Carton

100 mL
Multiple-Dose Vial
50 mg/mL

Sterile

NDC 0061-0851-03

Banamine ^®
(FLUNIXIN MEGLUMINE)

Injectable Solution
Veterinar y

Caution: Federal law restricts
this drug to use by or on the order of
a licensed veterinarian.

NADA #101-479, Approved by FDA.

Intervet
Schering-Plough Animal Health