Sulfadiazine / Trimethoprim

Antibiotic Sulfonamide + Diaminopyrimidine combination

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 15 mg/kg (combined dose) based on trimethoprim component q12h Duration: 5-7 days; for chronic infections up to 14-21 days
Notes: Administer with food to reduce GI upset. For urinary tract infections, ensure adequate water intake.
Cat PO 15 mg/kg (combined dose) q12h Duration: 5-7 days
Notes: Use with caution in cats with hepatic disease. May cause anorexia.
Horse PO 15-30 mg/kg (combined dose) q12h Duration: 5-7 days
Notes: Oral paste or powder. For severe infections, initial IV dose may be given.
Cattle PO 15-30 mg/kg (combined dose) q24h Duration: 3-5 days
Notes: For respiratory disease, use higher end. Withdrawal times must be observed.
Cattle IV 15-20 mg/kg (combined dose) q24h Duration: 3-5 days
Notes: Slow IV injection. Not for IM or SC due to tissue irritation.
Sheep/Goats PO 15-30 mg/kg (combined dose) q24h Duration: 3-5 days
Notes: Extra-label use; observe withdrawal times.
Rabbit PO 30 mg/kg (combined dose) q12h Duration: 7 days
Notes: May cause GI disturbances; monitor appetite.
Poultry PO (in water) 30 mg/kg (combined dose) or 0.5-1 g/L drinking water Continuous administration for 3-5 days Duration: 3-5 days
Notes: Ensure fresh solution daily. Withdrawal times for eggs and meat.

Clinical Indications & Species Uses

General Indications
  • Broad-spectrum antibacterial therapy for susceptible infections
  • Treatment of coccidiosis in various species
  • Adjunct therapy for toxoplasmosis
Dog (Canine)
  • Treatment of bacterial infections of the urinary tract, respiratory tract, skin and soft tissue, and gastrointestinal tract
  • Prostatitis
  • Bacterial enteritis
  • Coccidiosis (as an adjunct)
  • Nocardiosis
  • Toxoplasmosis (in combination with other agents)
Cat (Feline)
  • Treatment of bacterial infections of the urinary tract, respiratory tract, skin and soft tissue
  • Bacterial enteritis
  • Coccidiosis
  • Toxoplasmosis (in combination with clindamycin or pyrimethamine)
  • Nocardiosis
Horse (Equine)
  • Treatment of respiratory tract infections (e.g., strangles, pneumonia)
  • Urinary tract infections
  • Skin and soft tissue infections
  • Bacterial enteritis
  • Prophylaxis in surgical procedures
Cattle (Bovine)
  • Treatment of respiratory disease (e.g., bovine respiratory disease complex)
  • Bacterial pneumonia
  • Scours (diarrhea) caused by E. coli
  • Foot rot
  • Metritis
  • Mastitis (systemic therapy)
Small Ruminants (Sheep / Goat)
  • Treatment of respiratory infections
  • Enteritis
  • Mastitis
  • Foot rot
  • Coccidiosis (as an adjunct)
Rabbit & Small Mammals
  • Treatment of respiratory infections (e.g., Pasteurella multocida)
  • Urinary tract infections
  • Abscesses (as adjunct to surgical drainage)
  • Coccidiosis (as an adjunct)
Avian & Poultry
  • Treatment of colibacillosis
  • Salmonellosis
  • Pasteurellosis
  • Coccidiosis (as an adjunct)
  • Respiratory infections
Exotic & Other Species
  • Reptiles: respiratory and skin infections
  • Small mammals (ferrets, guinea pigs): respiratory and urinary infections
  • Zoo animals: various bacterial infections

Pharmacology & Mechanism of Action

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

Mechanism of Action: Sulfadiazine and trimethoprim act synergistically to inhibit bacterial folate synthesis. Sulfadiazine, a sulfonamide, competitively inhibits dihydropteroate synthase, preventing the incorporation of para-aminobenzoic acid (PABA) into dihydropteroic acid, an early step in folate synthesis. Trimethoprim, a diaminopyrimidine, inhibits dihydrofolate reductase, blocking the conversion of dihydrofolate to tetrahydrofolate. The combination produces a sequential blockade of the folate pathway, resulting in a bactericidal effect against susceptible organisms, whereas each agent alone is usually bacteriostatic.

Pharmacodynamics: The combination exhibits a broad spectrum of activity against many Gram-positive and Gram-negative aerobic bacteria, including Streptococcus spp., Staphylococcus spp., Escherichia coli, Klebsiella spp., Salmonella spp., Pasteurella spp., Bordetella spp., and some anaerobes. It is also effective against certain protozoa such as coccidia and Pneumocystis. The bactericidal activity is concentration-dependent and time-dependent, with optimal killing when the drug concentration exceeds the minimum inhibitory concentration (MIC) for a sufficient duration. The post-antibiotic effect is minimal.

⚡ Pharmacokinetics Summary

Absorption: Both sulfadiazine and trimethoprim are well absorbed from the gastrointestinal tract in most species after oral administration. Peak plasma concentrations are achieved within 2-4 hours in dogs and cats, and within 1-2 hours in horses. Absorption may be reduced in ruminants due to ruminal degradation, but oral dosing is still effective in calves with a functional rumen.
Distribution: Both drugs 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 placenta and are excreted in milk. Sulfadiazine is approximately 40-60% protein-bound in plasma, while trimethoprim is about 40-70% bound, depending on species.
Metabolism: Sulfadiazine is metabolized in the liver primarily by acetylation and glucuronidation. Trimethoprim is also metabolized in the liver, with oxidative metabolites. In ruminants, metabolism may be more extensive due to microbial activity in the rumen.
Excretion: Both drugs are excreted primarily in the urine, with sulfadiazine and its metabolites excreted by glomerular filtration and tubular secretion. Trimethoprim is also excreted in urine, with some biliary excretion. In animals with renal impairment, dosage adjustment may be necessary.
Half-Life: Dog: sulfadiazine ~10-13 h, trimethoprim ~4-6 h; Cat: sulfadiazine ~10-12 h, trimethoprim ~5-7 h; Horse: sulfadiazine ~3-4 h, trimethoprim ~2-3 h; Cattle: sulfadiazine ~2-4 h, trimethoprim ~1-2 h.
Bioavailability: Oral bioavailability is high in monogastric animals (70-90%), but lower in ruminants (50-70%) due to ruminal degradation. Injectable formulations are 100% bioavailable.
Protein Binding: Sulfadiazine: 40-60% bound; Trimethoprim: 40-70% bound, species-dependent.

Available Formulations & Strengths

Oral Tablet 120 mg (sulfadiazine 100 mg + trimethoprim 20 mg), 240 mg (200+40), 480 mg (400+80), 960 mg (800+160) (PO)
Oral Suspension Sulfadiazine 100 mg/mL + trimethoprim 20 mg/mL (PO)
Oral Paste Sulfadiazine 200 mg/mL + trimethoprim 40 mg/mL (PO)
Injectable Solution Sulfadiazine 200 mg/mL + trimethoprim 40 mg/mL (IV)
Powder for Oral Solution Sulfadiazine 100 g + trimethoprim 20 g per 100 g powder (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Known 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 (unless specific withdrawal times are followed)
  • Use in animals with blood dyscrasias (e.g., anemia, leukopenia)
  • Concurrent use with certain drugs that may potentiate toxicity (e.g., methotrexate)
  • Do not use in animals with a history of sulfonamide-induced keratoconjunctivitis sicca (dry eye)
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic or renal disease; adjust dose or interval.
  • Prolonged use may lead to superinfection with resistant organisms.
  • In horses, oral administration may cause diarrhea; monitor hydration.
  • In ruminants, oral administration may alter rumen flora; use with caution.
  • Ensure adequate water intake to prevent crystalluria.
  • May cause photosensitivity; avoid excessive sunlight exposure during treatment.
  • In cats, may cause anorexia and hepatic necrosis; monitor liver enzymes.
  • Do not use in animals with a history of sulfonamide-induced blood dyscrasias.
  • For food animals, observe withdrawal times.
  • Use in very young animals may affect bone marrow development; use with caution.

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea, anorexia)
  • Hypersensitivity reactions (skin rash, urticaria)
  • Crystalluria (especially with inadequate water intake)
  • Keratoconjunctivitis sicca (dry eye) in dogs (especially with chronic use)
  • Bone marrow suppression (leukopenia, thrombocytopenia) with prolonged use

Serious / Severe:

  • Acute hepatic necrosis (especially in cats)
  • Severe blood dyscrasias (agranulocytosis, aplastic anemia)
  • Stevens-Johnson syndrome (rare)
  • Anaphylaxis
  • Renal failure due to crystalluria or interstitial nephritis
  • Folate deficiency leading to megaloblastic anemia

Rare:

  • Polyarthritis
  • Meningoencephalitis
  • Thrombocytopenia
  • Hemolytic anemia (in animals with glucose-6-phosphate dehydrogenase deficiency)
  • 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
Methotrexate Trimethoprim inhibits dihydrofolate reductase, increasing the risk of methotrexate toxicity. High
Phenytoin Sulfonamides may inhibit phenytoin metabolism, increasing phenytoin levels and toxicity. Moderate
Cyclosporine Trimethoprim may increase the risk of nephrotoxicity when used with cyclosporine. Moderate
Procainamide Trimethoprim may reduce renal excretion of procainamide, increasing its levels. Moderate
Potassium-sparing diuretics (e.g., spironolactone) Trimethoprim may cause hyperkalemia when combined with potassium-sparing diuretics. Moderate
Sulfonylureas (e.g., glipizide) Sulfonamides may enhance the hypoglycemic effect of sulfonylureas. Mild
Methenamine May increase the risk of crystalluria due to acidification of urine. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Anorexia
  • Vomiting
  • Diarrhea
  • Lethargy
  • Ataxia
  • Tremors
  • Seizures (in severe cases)
  • Crystalluria and hematuria
  • Bone marrow suppression (with chronic overdose)

Emergency Treatment Protocol: Treatment is primarily supportive. Induce emesis if recent oral ingestion and the animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids to enhance renal excretion and prevent crystalluria. Monitor renal function, liver enzymes, and blood cell counts. In severe cases, consider hemodialysis or peritoneal dialysis. Discontinue the drug immediately. For bone marrow suppression, administer folinic acid (leucovorin) at 1-5 mg/kg IV or IM, repeated as needed.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 4 days🥚 Eggs: 5 days

Withdrawal times vary by country and formulation. Always follow label or veterinary guidance. For cattle, meat withdrawal is typically 7 days; milk 4 days. For poultry, eggs 5 days, meat 5 days. For swine, meat 5 days. Extra-label use may require extended withdrawal times.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), 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 away from direct sunlight.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs, cats, horses, cattle, and swine in various formulations. Some products are approved for poultry. Check specific product labels.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with a valid veterinary-client-patient relationship, but requires extended withdrawal times and may not be used in feed. In non-food animals, extra-label use is allowed. In the EU, similar rules apply under Regulation (EC) No 470/2009.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Sulfadiazine/trimethoprim is a valuable broad-spectrum antibiotic in veterinary practice. It is particularly useful for urinary tract infections, respiratory infections, and skin infections. The combination is bactericidal and has a wide margin of safety when used at recommended doses. However, it is essential to ensure adequate hydration to prevent crystalluria, especially in animals with acidic urine. In cats, monitor for signs of anorexia and hepatic toxicity. In horses, oral administration may cause diarrhea; consider alternative routes if GI upset occurs. For food animals, strict adherence to withdrawal times is critical. The drug is not recommended for use in pregnant animals unless the benefits outweigh risks. Always perform culture and sensitivity testing when possible to ensure efficacy. Clinical monitoring should include complete blood counts and serum biochemistry for prolonged therapy.

References & Literature

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