Sulfadimethoxine/Ormetoprim
Sulfadimethoxine/ormetoprim is a **potentiated sulfonamide antimicrobial** FDA-approved for the treatment of skin and soft tissue infections in dogs caused by susceptible strains of *Staphylococcus aureus* and *E. coli*. **Key Clinical Features:** - **Convenience:** Can be dosed once daily, unlike many other sulfa drugs. - **Tolerability:** May have fewer adverse effects in dogs compared to trimethoprim/sulfadiazine. - **Limitations:** It does not penetrate the prostate well, making it ineffective for bacterial prostatitis. It is also generally more expensive than generic trimethoprim/sulfa combinations. > **Clinical Pearl:** While resistance develops more slowly to the combination than to either drug alone, plasmid-mediated resistance is common in gram-negative organisms.
Mechanism: Sulfadimethoxine/ormetoprim is **bactericidal** due to the synergistic, sequential inhibition of enzymes in the bacterial folic acid synthesis pathway. - **Sulfadimethoxine** (a sulfonamide) acts as a false substrate, competitively inhibiting the conversion of para-aminobenzoic acid (PABA) → dihydrofolic acid (DFA). - **Ormetoprim** (a diaminopyrimidine) blocks the subsequent conversion of DFA → tetrahydrofolic acid (THFA) by reversibly inhibiting the enzyme **dihydrofolate reductase**. This dual blockade halts bacterial thymidine synthesis, ultimately preventing DNA replication. It has a broad spectrum of activity against many Gram-positive (e.g., *Staphylococcus*, *Streptococcus*, *Nocardia*) and Gram-negative organisms (excluding *Pseudomonas aeruginosa*), as well as certain protozoa (*Pneumocystis*, *Coccidia*, *Toxoplasma*).
Dosing by species
- Susceptible infections · Medicated premix: 113.5 grams sulfadimethoxine and 68.1 grams ormetoprim per pound in 50 lb bags · PO · Continuous in feed · Varies · FDA-approved for chickens (broilers, replacements), turkeys, ducks, & Chukar partridges. 5-day slaughter withdrawal. Do not feed to chickens over 16 weeks of age, or turkeys/ducks producing eggs for food.
- Susceptible infections (skin and soft tissue) · Initially 55 mg/kg (combined drug) PO on the first day of therapy, then 27.5 mg/kg PO once daily for at least 2 days after remission of clinical signs. Not approved for treatment longer than 21 days. · PO · q24h · Up to 21 days · Dose is based on combined drug weight.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Hypersensitivity to sulfonamides, thiazides, or sulfonylurea agents
- Severe renal or hepatic impairment
- Marked liver parenchymal damage
- Blood dyscrasias
- Doberman Pinschers (highly susceptible to sulfonamide-induced poly-systemic immune complex disease)
Adverse effects
- Keratoconjunctivitis sicca (KCS/dry eye) - potentially irreversible
- Acute neutrophilic hepatitis with icterus
- Vomiting
- Anorexia
- Diarrhea
- Fever
- Hemolytic anemia
- Urticaria
- Polyarthritis
- Facial swelling
- Polydipsia and polyuria
- Cholestasis
- Hypersensitivity reactions (Type I anaphylaxis or Type III serum sickness)
- Hypothyroidism (with extended use)
- Crystalluria and hematuria (especially in cats)
- Leukopenias and anemias
Drug interactions
- Various (Refer to Trimethoprim/Sulfa) · Specific interactions are not explicitly noted for this combination, but it is expected to share the interaction profile of trimethoprim/sulfa (e.g., potential antagonism with cyclosporine, increased risk of bleeding with anticoagulants).
Monitoring
- Clinical efficacy and resolution of infection
- Adverse effects (especially signs of hypersensitivity or liver issues)
- Tear production via Schirmer Tear Test in dogs (baseline, at 5 days post-initiation, and then every 2-3 weeks)
Overdose
In experimental dog studies, doses **>80 mg/kg** resulted in slight tremors and increased motor activity. Higher doses may cause depression, anorexia, or seizures. **Treatment:** For very high oral overdoses, empty the gut using standard precautions and protocols. Treat clinical signs supportively and symptomatically.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.