Sulfamethoxazole / Trimethoprim

Antibiotic Sulfonamide + Diaminopyrimidine combination

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 15-30 mg/kg (combined dose) based on trimethoprim component q12h Duration: 5-14 days depending on infection
Notes: For UTIs, 5-7 days; for pyoderma, 10-14 days; for prostatitis, 4-6 weeks. Administer with food to reduce GI upset.
Cat PO 15-30 mg/kg (combined dose) q12h Duration: 5-14 days
Notes: Use with caution in cats with renal disease. May cause anorexia and salivation.
Horse PO 30 mg/kg (combined dose) q12h Duration: 5-10 days
Notes: Oral absorption is variable; consider IV for severe infections. Monitor for diarrhea.
Cattle PO 30 mg/kg (combined dose) q24h Duration: 3-5 days
Notes: For BRD, may be used for 3-5 days. Observe withdrawal times for meat and milk.
Cattle IV 15-20 mg/kg (combined dose) q12h Duration: 3-5 days
Notes: Use for severe infections when oral administration is not feasible.
Sheep/Goat PO 30 mg/kg (combined dose) q24h Duration: 3-5 days
Notes: May cause diarrhea in ruminants; monitor hydration.
Rabbit PO 30 mg/kg (combined dose) q12h Duration: 5-7 days
Notes: Use with caution due to potential GI dysbiosis. Ensure adequate hydration.
Bird/Poultry PO (in water or feed) 50-100 mg/kg (combined dose) per day q24h Duration: 3-5 days
Notes: Dose may be administered in drinking water. Ensure fresh solution daily.
Reptiles PO 30 mg/kg (combined dose) q24-48h Duration: 7-14 days
Notes: Dosing interval may be extended in reptiles due to slower metabolism.

Clinical Indications & Species Uses

General Indications
  • Treatment of infections caused by susceptible organisms
  • Empiric therapy for common bacterial infections when susceptibility is likely
  • Prophylaxis in certain surgical procedures (off-label)
Dog (Canine)
  • Urinary tract infections (UTIs)
  • Respiratory infections (e.g., pneumonia, kennel cough)
  • Skin and soft tissue infections (pyoderma, abscesses)
  • Gastrointestinal infections (e.g., salmonellosis, bacterial diarrhea)
  • Prostatitis
  • Otitis externa (when caused by susceptible bacteria)
  • Opportunistic infections (e.g., nocardiosis, actinomycosis)
  • Toxoplasmosis (in combination with other agents)
  • Pneumocystis pneumonia (in immunocompromised dogs)
Cat (Feline)
  • Urinary tract infections (UTIs)
  • Respiratory infections (e.g., feline upper respiratory infection complex)
  • Skin and soft tissue infections (abscesses, wounds)
  • Gastrointestinal infections (e.g., salmonellosis)
  • Toxoplasmosis (in combination with clindamycin or pyrimethamine)
  • Nocardiosis
  • Bartonellosis (in combination with other antibiotics)
Horse (Equine)
  • Respiratory infections (e.g., pneumonia, pleuropneumonia)
  • Urinary tract infections
  • Skin and soft tissue infections
  • Bacterial enteritis (e.g., salmonellosis)
  • Septicemia in foals
  • Prophylaxis in surgical procedures (off-label)
Cattle (Bovine)
  • Bovine respiratory disease complex (BRD)
  • Pneumonia (e.g., Pasteurella, Mannheimia)
  • Bacterial diarrhea (e.g., colibacillosis, salmonellosis)
  • Metritis
  • Foot rot (interdigital necrobacillosis)
Small Ruminants (Sheep / Goat)
  • Respiratory infections (e.g., pneumonia)
  • Enteritis (e.g., colibacillosis, salmonellosis)
  • Mastitis (in sheep and goats)
  • Foot rot
  • Metritis
Rabbit & Small Mammals
  • Respiratory infections (e.g., Pasteurella multocida)
  • Urinary tract infections
  • Gastrointestinal infections (e.g., bacterial enteritis)
  • Skin infections (abscesses)
Avian & Poultry
  • Respiratory infections (e.g., colibacillosis, pasteurellosis)
  • Enteritis (e.g., salmonellosis)
  • Systemic infections (e.g., septicemia)
  • Infections caused by susceptible Gram-negative bacteria
Exotic & Other Species
  • Reptiles: Respiratory infections, stomatitis, abscesses
  • Small mammals (e.g., ferrets, guinea pigs): Respiratory infections, urinary tract infections
  • Amphibians: Bacterial infections (limited data)

Pharmacology & Mechanism of Action

Drug Class: Antibiotic | Pharmacological Group: Sulfonamide + Diaminopyrimidine combination

Mechanism of Action: Sulfamethoxazole and trimethoprim are synergistic antimicrobials that inhibit sequential steps in bacterial folate synthesis. Sulfamethoxazole, a sulfonamide, competitively inhibits dihydropteroate synthase, preventing the incorporation of para-aminobenzoic acid (PABA) into dihydropteroic acid. Trimethoprim, a diaminopyrimidine, inhibits dihydrofolate reductase, blocking the reduction of dihydrofolate to tetrahydrofolate. The combination produces a bactericidal effect by causing a sequential blockade of folic acid metabolism, which is essential for bacterial DNA synthesis and cell growth. This synergy broadens the spectrum and reduces the development of resistance.

Pharmacodynamics: The combination exhibits bactericidal activity against a wide range of Gram-positive and Gram-negative aerobic bacteria, including many Enterobacteriaceae, staphylococci, streptococci, and some anaerobes. It is effective against pathogens such as Escherichia coli, Klebsiella spp., Proteus mirabilis, Salmonella spp., Pasteurella multocida, and Bordetella bronchiseptica. The optimal synergistic ratio is 1:5 (trimethoprim:sulfamethoxazole) in plasma and tissues. The drug is generally bacteriostatic at lower concentrations but bactericidal at therapeutic levels. It is also effective against some protozoa like Pneumocystis jirovecii and Toxoplasma gondii.

⚡ Pharmacokinetics Summary

Absorption: In most species, sulfamethoxazole/trimethoprim is well absorbed after oral administration, with peak plasma concentrations occurring within 1-4 hours. The oral bioavailability is approximately 85-100% in dogs and cats, but may be lower in ruminants due to ruminal degradation. In horses, oral absorption is variable and may be less reliable. The drug is also absorbed after intramuscular and subcutaneous administration, but oral administration is preferred for systemic infections.
Distribution: Both components are widely distributed throughout the body, including into tissues and fluids such as the lungs, kidneys, prostate, cerebrospinal fluid (CSF), and synovial fluid. They cross the blood-brain barrier to some extent, especially in the presence of inflammation. The volume of distribution is moderate, and both drugs penetrate intracellularly. Protein binding is moderate: sulfamethoxazole is about 60-70% bound, while trimethoprim is about 40-50% bound in dogs and cats.
Metabolism: Sulfamethoxazole is metabolized in the liver primarily by acetylation and glucuronidation, producing inactive metabolites. Trimethoprim is also metabolized in the liver to a lesser extent, with oxidative metabolites. In ruminants, metabolism may be more extensive due to hepatic and ruminal activity.
Excretion: Both drugs and their metabolites are excreted primarily in the urine via glomerular filtration and tubular secretion. A significant portion of the dose is eliminated in the feces via biliary excretion. In animals with renal impairment, dosage adjustment may be necessary to avoid accumulation.
Half-Life: The elimination half-life varies by species: Dogs: approximately 10-12 hours; Cats: approximately 10-12 hours; Horses: approximately 2-4 hours; Cattle: approximately 2-4 hours; Sheep/Goats: approximately 2-4 hours; Rabbits: approximately 2-4 hours; Birds: approximately 2-4 hours.
Bioavailability: Oral bioavailability is high in dogs and cats (85-100%), but lower in horses (approximately 50-70%) and ruminants (variable, often less than 50% due to ruminal degradation).
Protein Binding: Sulfamethoxazole: 60-70% in dogs and cats; Trimethoprim: 40-50% in dogs and cats. Protein binding may be lower in other species.

Available Formulations & Strengths

Oral Tablet 80 mg trimethoprim/400 mg sulfamethoxazole (TMP/SMX 80/400), 160 mg/800 mg (TMP/SMX 160/800) (PO)
Oral Suspension 40 mg trimethoprim/200 mg sulfamethoxazole per 5 mL (PO)
Injectable Solution 80 mg trimethoprim/400 mg sulfamethoxazole per mL (for IV use) (IV)
Oral Paste (for horses) Various concentrations, e.g., 100 mg trimethoprim/500 mg sulfamethoxazole per mL (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to sulfonamides or trimethoprim
  • Severe hepatic or renal impairment (unless dosage adjusted)
  • Pregnancy (especially in the last trimester) due to potential teratogenic effects
  • Lactating dairy animals (if milk is for human consumption) due to withdrawal times
  • Use in animals with blood dyscrasias (e.g., anemia, leukopenia)
  • Concurrent use with methenamine (may increase risk of crystalluria)
  • Use in animals with a history of sulfonamide-induced adverse reactions (e.g., keratoconjunctivitis sicca in dogs)
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic or renal disease; adjust dose if necessary.
  • Prolonged use may result in superinfection with resistant organisms.
  • In dogs, sulfonamides can cause keratoconjunctivitis sicca (KCS); monitor tear production during long-term therapy.
  • In horses, oral administration may cause diarrhea; monitor hydration.
  • In ruminants, oral administration may disrupt ruminal flora; use with caution.
  • Ensure adequate water intake to prevent crystalluria.
  • Avoid use in animals with a history of sulfonamide sensitivity.
  • In cats, may cause anorexia, vomiting, and salivation; use with caution.
  • In reptiles, dosing intervals may need to be extended due to slower metabolism.
  • For food animals, observe withdrawal times.

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea, anorexia)
  • Hypersensitivity reactions (skin rash, urticaria)
  • Crystalluria (especially in dehydrated animals)
  • Salivation (in cats)
  • Bone marrow suppression (with prolonged use)

Serious / Severe:

  • Keratoconjunctivitis sicca (KCS) in dogs
  • Blood dyscrasias (thrombocytopenia, leukopenia, anemia)
  • Hepatotoxicity
  • Renal toxicity (crystalluria, interstitial nephritis)
  • Stevens-Johnson syndrome (rare)
  • Anaphylaxis (rare)

Rare:

  • Folate deficiency (megaloblastic anemia)
  • Polyneuropathy
  • Pancreatitis
  • Allergic myocarditis
  • Eosinophilic pneumonitis

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Warfarin and other anticoagulants Sulfonamides may potentiate the anticoagulant effect by displacing protein-bound warfarin and inhibiting its metabolism. High
Phenytoin Sulfamethoxazole may inhibit phenytoin metabolism, increasing phenytoin levels and toxicity. Moderate
Methotrexate Both drugs inhibit folate metabolism; concurrent use may increase the risk of bone marrow suppression and folate deficiency. High
Methenamine Methenamine acidifies urine, increasing the risk of sulfonamide crystalluria. Moderate
Cyclosporine Sulfonamides may increase cyclosporine levels and nephrotoxicity. Moderate
Digoxin Trimethoprim may increase digoxin levels in some patients, potentially leading to toxicity. Moderate
Potassium-sparing diuretics (e.g., spironolactone) Trimethoprim can cause hyperkalemia; concurrent use may increase the risk. Moderate
Sulfonylureas (e.g., glipizide) Sulfonamides may potentiate the hypoglycemic effect of sulfonylureas. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Anorexia
  • Vomiting
  • Diarrhea
  • Ataxia
  • Depression
  • Crystalluria and hematuria
  • Bone marrow suppression (with chronic overdose)
  • Hepatotoxicity
  • Renal failure

Emergency Treatment Protocol: Treatment is primarily supportive. Induce emesis if recent ingestion and the animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids to enhance renal excretion and prevent crystalluria. Monitor renal and hepatic function, blood cell counts, and electrolytes. In severe cases, consider hemodialysis or peritoneal dialysis. Folinic acid (leucovorin) may be administered to counteract folate depletion, especially in cases of bone marrow suppression. Symptomatic treatment for vomiting and diarrhea may be necessary.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 96 days

Withdrawal times vary by country and formulation. In the US, the label for cattle indicates a meat withdrawal of 7 days and a milk withdrawal of 96 hours (4 days). For sheep and goats, withdrawal times may be longer; consult local regulations. Not approved for use in laying hens in the US; therefore, egg withdrawal is not established.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), with excursions permitted between 15-30°C (59-86°F).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Keep container tightly closed. Do not freeze oral suspensions. Injectable solutions should be stored at room temperature and protected from light.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats in the US (e.g., Tribrissen®). Not approved for food animals in the US, but may be used extra-label under AMDUCA.

Extra-Label (Off-Label) Use: In the US, sulfamethoxazole/trimethoprim is not FDA-approved for use in food animals; therefore, extra-label use in food animals requires a valid veterinary-client-patient relationship and must comply with AMDUCA. For non-food animals, extra-label use is permitted under veterinary discretion. In the EU, similar regulations apply under the cascade system.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Sulfamethoxazole/trimethoprim is a broad-spectrum antibiotic commonly used in veterinary practice for a variety of infections. It is particularly useful for urinary tract infections, respiratory infections, and skin infections. The combination is synergistic and bactericidal, but resistance can develop, so culture and sensitivity testing is recommended for serious infections. In dogs, long-term use may cause KCS, so tear production should be monitored. In cats, it may cause gastrointestinal upset and salivation. In horses, oral absorption is variable, so parenteral administration may be preferred for severe infections. In food animals, withdrawal times must be observed. Always ensure adequate hydration to prevent crystalluria. The drug is generally well-tolerated, but adverse effects can occur, especially with prolonged use. It is important to consider species-specific dosing and contraindications.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)