Tribrissen 400 Oral Paste

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  • Tribrissen 400 Oral Paste Indications
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Tribrissen 400 Oral Paste

This treatment applies to the following species:
Manufacturer: Intervet/Merck Animal Health

FOR USE IN HORSES

NADA #131-918, Approved by FDA.

Tribrissen 400 Oral Paste Caution

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

Description

TRIBRISSEN 400 Oral Paste contains 67 mg trimethoprim and 333 mg sulfadiazine per gram.

TRIBRISSEN Oral Paste is a combination of trimethoprim and sulfadiazine in the ratio of 1 part to 5 parts by weight, which provides effective antibacterial activity against a wide range of bacterial infections in animals.

Trimethoprim is 2,4 diamino-5-(3,4,5-trimethoxybenzyl) pyrimidine.

ACTIONS: Microbiology: Trimethoprim blocks bacterial production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the enzyme dihydrofolate reductase.

Sulfadiazine, in common with other sulfonamides, inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid.

TRIBRISSEN Oral Paste thus imposes a sequential double blockade on bacterial metabolism. This deprives bacteria of nucleic acids and proteins essential for survival and multiplication, and produces a high level of antibacterial activity which is usually bactericidal.

Although both sulfadiazine and trimethoprim are antifolate, neither affects the folate metabolism of animals. The reasons are: animals do not synthesize folic acid and cannot, therefore, be directly affected by sulfadiazine; and although animals must reduce their dietary folic acid to tetrahydrofolic acid, trimethoprim does not affect this reduction because its affinity for dihydrofolate reductase of mammals is significantly less than that for the corresponding bacterial enzyme.

TRIBRISSEN Oral Paste is active against a wide spectrum of bacterial pathogens, both gram-positive and gram-negative. The following in vitro data are available, but their clinical significance is unknown. In general, species of the following genera are sensitive to TRIBRISSEN Oral Paste:

Very Sensitive: Escherichia, Streptococcus, Proteus, Salmonella, Pasteurella, Shigella, Haemophilus

Sensitive: Staphylococcus, Neisseria, Klebsiella, Fusiformis, Corynebacterium, Clostridium, Bordetella

Moderately Sensitive: Moraxella, Nocardia, Brucella

Not Sensitive: Mycobacterium, Leptospira, Pseudomonas. Erysipelothrix

As a result of the sequential double blockade of the metabolism of susceptible organisms by trimethoprim and sulfadiazine, the minimum inhibitory concentration (MIC) of TRIBRISSEN Oral Paste is markedly less than that of either of the components used separately. Many strains of bacteria that are not susceptible to one of the components are susceptible to TRIBRISSEN Oral Paste.

A synergistic effect between trimethoprim and sulfadiazine in combination has been shown experimentally both in vitro and in vivo (in dogs).

TRIBRISSEN Oral Paste is bactericidal against susceptible strains and is often effective against sulfonamide-resistant organisms. In vitro sulfadiazine is usually only bacteriostatic.

The precise in vitro MIC of the combination varies with the ratio of the drugs present, but action of TRIBRISSEN Oral Paste occurs over a wide range of ratios with an increase in the concentration of one of its components compensating for a decrease in the other. It is usual, however, to determine MICs using a constant ratio of 1 part trimethoprim in 20 parts of the combination.

The following table shows MICs, using the above ratio, of bacteria which were susceptible to both trimethoprim (TMP) and sulfadiazine (SDZ). The organisms are those most commonly involved in conditions for which TRIBRISSEN Oral Paste is indicated:

AVERAGE MINIMUM INHIBITORY CONCENTRATION (MIC-mcg/mL)

Bacteria

TMP
Alone

SDZ
Alone

TMP/SDZ

TMP

SDZ

Escherichia coli

0.31

26.5

0.07

1.31

Proteus species

1.3

24.5

0.15

2.85

Staphylococcus aureus

0.6

17.6

0.13

2.47

Pasteurella species

0.06

20.1

0.03

0.56

Salmonella species

0.15

61.0

0.05

0.95

β Streptococcus

0.5

24.5

0.15

2.85

The following table demonstrates the marked effect of the trimethoprim and sulfadiazine combination against sulfadiazine-resistant strains of normally susceptible organisms:

AVERAGE MINIMUM INHIBITORY CONCENTRATION OF SULFADIAZINE-RESISTANT STRAINS (MIC-mcg/mL)

Bacteria

TMP
Alone

SDZ
Alone

TMP/SDZ

TMP

SDZ

Escherichia coli

0.32

>245

0.27

5.0

Proteus species

0.66

>245

0.32

6.2

Susceptibility Testing: In testing susceptibility to TRIBRISSEN Oral Paste, it is essential that the medium used does not contain significant amounts of interfering substances which can bypass the metabolic blocking action, eg, thymidine or thymine.

The standard SxT disc is appropriate for testing by the disc diffusion method.

Pharmacology: Following oral administration, TRIBRISSEN Oral Paste is rapidly absorbed and widely distributed throughout body tissues. Concentrations of trimethoprim are usually higher in tissues than in the blood. The levels of trimethoprim are high in the lungs, kidney, and liver, as would be expected from its physical properties.

Serum trimethoprim concentrations in horses following oral administration indicate rapid absorption of the drug; peak concentrations occur in 2 to 3 hours. The mean serum elimination half-life is 2 to 3 hours. Sulfadiazine absorption is slower, requiring 3 to 6 hours to reach peak concentrations. The mean serum elimination half-life for sulfadiazine is about 7 hours.

Usually, the concentration of an antibacterial in the blood and the in vitro MIC of the infecting organism indicate an appropriate period between doses of a drug. This does not hold entirely for TRIBRISSEN Oral Paste because trimethoprim, in contrast to sulfadiazine, localizes in tissues and therefore, its concentration and ratio to sulfadiazine are higher there than in blood.

The following table shows the average serum concentrations of trimethoprim and sulfadiazine in 11 adult horses observed on Day 3 of three consecutive daily doses of TRIBRISSEN 400 Oral Paste:

AVERAGE SERUM CONCENTRATION (mcg/mL)

Trimethoprim (5 mg/kg)

Sulfadiazine (25 mg/kg)

1 hr

3 hr

6 hr

10 hr

24 hr

1 hr

3 hr

6 hr

10 hr

24 hr

0.71

0.95

0.37

0.04

<0.04

8.0

15.8

9.9

5.6

0.6

Excretion of TRIBRISSEN Oral Paste is chiefly by the kidneys, by both glomerular filtration and tubular secretion. Urine concentrations of both trimethoprim and sulfadiazine are severalfold higher than blood concentrations. Neither trimethoprim nor sulfadiazine interferes with the excretion pattern of the other.

Tribrissen 400 Oral Paste Indications and Usage

TRIBRISSEN 400 Oral Paste is indicated in horses where potent systemic antibacterial action against sensitive organisms is required. TRIBRISSEN 400 Oral Paste is indicated where control of bacterial infections is required during treatment of: Acute Strangles, Respiratory Tract Infections, Acute Urogenital Infections, Wound Infections And Abscesses.

TRIBRISSEN Oral Paste is well tolerated by foals.

Contraindications

TRIBRISSEN Oral Paste should not be used in horses showing marked liver parenchymal damage, blood dyscrasias, or in those with a history of sulfonamide sensitivity.

Warning

Do not use in horses intended for human consumption.

Adverse Reactions

During clinical trials, one case of anorexia and one case of loose feces following treatment with the drug were reported.

Individual animal hypersensitivity may result in local or generalized reactions, sometimes fatal. Anaphylactoid reactions, although rare, may also occur.

Antidote: Epinephrine.

Post Approval Experience: Horses have developed diarrhea during TRIBRISSEN Oral Paste treatment, which could be fatal. If fecal consistency changes during TRIBRISSEN Oral Paste therapy, discontinue treatment immediately and contact your veterinarian.

Precautions

Water should be readily available to horses receiving sulfonamide therapy.

ANIMAL SAFETY: Toxicity is low. The acute toxicity (LD50) of TRIBRISSEN Oral Paste is more than 5 g/kg orally in rats and mice. No significant changes were recorded in rats given doses of 600 mg/kg per day for 90 days.

Horses treated intravenously with TRIBRISSEN 48% Injection have tolerated up to five times the recommended daily dose for 7 days or on the recommended daily dose for 21 consecutive days without clinical effects or histopathological changes.

Lengthening of clotting time was seen in some of the horses on high or prolonged dosing in one of two trials. The effect, which may have been related to a resolving infection, was not seen in a second similar trial.

Slight to moderate reductions in hematopoietic activity following high, prolonged dosage in several species have been recorded. This is usually reversible by folinic acid (leucovorin) administration or by stopping the drug. During long-term treatment of horses, periodic platelet counts and white and red blood cell counts are advisable.

In rare instances, horse have developed diarrhea during TRIBRISSEN Oral Paste treatment. If fecal consistency changes during TRIBRISSEN Oral Paste therapy, discontinue treatment immediately and institute appropriate symptomatic measures.

TERATOLOGY: The effect of TRIBRISSEN 400 Oral Paste on pregnancy has not been determined. Studies to date show there is no detrimental effect on stallion spermatogenesis with or following the recommended dose of TRIBRISSEN 400 Oral Paste.

Dosage and Administration

The recommended dose is 3.75 g TRIBRISSEN 400 Oral Paste per 110 lbs (50 kg) body weight per day. Administer orally once a day by means of the Dial-A-Dose®* syringe. Each marking on the syringe doses 110 lbs (50 kg) body weight. When administering TRIBRISSEN 400 Oral Paste, the oral cavity should be empty. Deposit paste on back of tongue by depressing plunger that has been previously set to deliver the correct dose.

The usual course of treatment is a single, daily dose for 5 to 7 days.

Continue acute infection therapy for 2 or 3 days after clinical signs have subsided.

If no improvement of acute infections is seen in 3 to 5 days, reevaluate the diagnosis.

TRIBRISSEN 400 Oral Paste may be used alone or in conjunction with intravenous dosing. Following treatment with TRIBRISSEN 48% Injection, therapy can be maintained using oral paste.

A complete blood count should be done periodically in patients receiving TRIBRISSEN Oral Paste for prolonged periods. If significant reduction in the count of any formed blood element is noted, treatment with TRIBRISSEN Oral Paste should be discontinued.

STORAGE: Store at 15°-30°C (59°-86°F).

HOW SUPPLED: TRIBRISSEN 400 Oral Paste is available in 37.5 g Dial-A-Dose®* syringes.

KEEP OUT OF REACH OF CHILDREN.

*Trademark: Plas-Pak Industries, Inc.

Made in Ireland.

Copyright © 1997, 1998, Schering-Plough Animal Health Corp., Union, NJ 07083. All rights reserved.

Net wt.

NDC

 

37.5 g

0061-5069-01

25262507 Rev. 3/05

NAC No.: 10471983

MERCK ANIMAL HEALTH
Intervet Inc.

556 MORRIS AVE., SUMMIT, NJ, 07901
Customer Service:   800-521-5767
Order Desk:   800-648-2118
Technical Service (Companion Animal):   800-224-5318
Technical Service (Livestock):   800-211-3573
Fax:   908-473-5560
Website:   www.merck-animal-health-usa.com
Every effort has been made to ensure the accuracy of the Tribrissen 400 Oral Paste information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the US product label or package insert.

Copyright © 2014 North American Compendiums. Updated: 2014-09-05

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