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Trimethoprim /Sulfamethoxazole (Tribrissen®)

By: Dr. Nicholas Dodman

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Overview

  • Trimethoprim and sulfamethoxazole are two antibiotics that work together to create an optimal effect.
  • Trimethoprim's method of action is to block the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the enzyme dihydrofolate reductase. This binding is much stronger for the bacterial enzyme than the corresponding mammalian enzyme.
  • Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid. Thus the combination of trimethoprim and sulfamethoxazole inhibits two consecutive steps in the production of nucleic acids and proteins.
  • Trimethoprim and sulfamethoxazole is a prescription drug and can only be obtained from a veterinarian or by prescription from a veterinarian.

    Brand Names and Other Names

  • This drug is registered for use in humans, dogs, horses, cattle, and swine.
  • Human formulations: Bactrim® (Roche), Septra® (GlaxoWellcome), Cotrim Pediatric® (Lemmon), Sulfatrim® (URL and others), and generic preparations of Trimethoprim and Sulfamethoxazole.
  • Veterinary formulations: Tribrissen® and Tribrissen 400 Oral Paste (Schering-Plough), Di-Biotic® (Phoenix Pharmaceutical), Uniprim® Powder (Macleod), Tucoprim® Powder (Pharmacia & Upjohn), Borgal® (Hoechst), and generics.

    Uses of Trimethoprim and Sulfamethoxazole

    Trimethoprim and sulfamethoxazole is used in both dogs and cats to treat a variety of infections including:

  • Urinary tract infections caused by susceptible strains of E. coli, Klebsiella, and Enterobacter species.
  • Enteritis caused by susceptible organisms (e.g. Shigella)
  • Pneumonia
  • Otitis media
  • Prostatitis
  • Coccidiosis
  • Kennel cough (Bordatella bronchiseptica)
  • Skin infections (esp. Staphylococcal)

    Precautions and Side Effects

  • Trimethoprim and sulfamethoxazole should not be used in animals with known hypersensitivity or allergy to these or other sulfa drugs.
  • Trimethoprim and sulfamethoxazole should not be used in pregnant animals.
  • While generally safe and effective when prescribed by a veterinarian, trimethoprim and sulfamethoxazole can cause side effects in some animals. The following are known side effects organized by organ system:

  • Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia.
  • Allergic Reactions: Epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria, and rash. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported in humans.
  • Gastrointestinal: Hepatitis, including cholestatic jaundice and hepatic necrosis, elevation of serum transaminases and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia.
  • Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, and crystalluria.
  • Metabolic: Hyperkalemia, hyponatremia.
  • Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.
  • CNS: Depression, apathy, anxiety.
  • Endocrine: Cross-sensitivity may exist with diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. Diuresis and hypoglycemia have occurred in human patients receiving sulfonamides. Trimethoprim-sulfamethoxazole combination has been demonstrated to reduce thyroid hormone levels to below the normal reference range.
  • Musculoskeletal: Arthralgia and myalgia.
  • Respiratory System: Cough, dyspnea, and pulmonary infiltrates.

    Drug Interactions

  • Trimethoprim and sulfamethoxazole may interact with other medications. Consult with your veterinarian to determine if other drugs your pet is receiving could interact with trimethoprim and sulfamethoxazole.
  • When injectable preparations are mixed with other drugs, incompatibility may occur.
  • Sulfamethoxazole and trimethoprim may inhibit the hepatic metabolism of phenytoin.
  • Sulfonamides can displace methotrexate from plasma protein binding sites, increasing free methotrexate concentrations.
  • Other drug interactions occur when trimethoprim-sulfamethoxazole is coadministered with anticoagulants (prothrombin time increased), cyclopsporine (decreased therapeutic efficacy of cylcosporine), and diuretics (increased incidence of thrombocytopenia with purpura in humans).
  • In addition, the hypoglycemic response to sulfonureas may be increased and serum levels of zidovuldine may be increased.

    How Trimethoprim & Sulphamethoxazole is Supplied

    There are several human and veterinary preparations available.

    Human preparations include:

  • Tablets:
    -80 mg trimethoprim and 400 mg sulfamethoxazole
    -160 mg trimethoprim and 800 mg sulfamethoxazole
  • Oral Suspension:
    -40 mg trimethoprim and 200 mg sulfamethoxazole per 5 mL
  • Injection:
    -16 mg/mL trimethoprim and 80 mg/mL sulfamethoxazole per 5 mL
    -80 mg/mL trimethoprim and 400 mg/mL sulfamethoxazole per 5 mL
  • Powder:
    -67 mg trimethoprim and 333 mg sulfamethoxazole per g.

    Veterinary preparations include:

  • Tablets:
    -5 mg trimethoprim and 25 mg sulfamethoxazole
    -20 mg trimethoprim and 100 mg sulfamethoxazole
    -80 mg trimethoprim and 400 mg sulfamethoxazole
    -160 mg trimethoprim and 800 mg sulfamethoxazole
  • Oral Paste (for horses):
    -67 mg trimethoprim and 333 mg sulfamethoxazole
  • Injection (for horses):
    -48% in 100 mL vials

    Dosing Information

  • Medication should never be administered without first consulting your veterinarian.
  • Doses of trimethoprim and sulfamethoxazole vary depending on the reason for prescribing.
  • The duration of administration depends on the condition being treated, response to the medication and the development of any adverse effects. Be certain to complete the prescription unless specifically directed by your veterinarian. Even if your pet feels better, the entire treatment plan should be completed to prevent relapse.
  • In dogs and cats, the usual dose is 12.5 to 50 mg per pound (25 to 100 mg/kg) every 24 hours orally, subcutaneously, intramuscularly or intravenously for 10 to 20 days.



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