Sulfamethoxazole/Trimethoprim

• (sul-fa-dye-a-zeen; sul-fa-meth-ox-a-zole/trye-meth-ohe-prim)

• TMS, Co-trimoxazole, EquiSul-SDT®
• Potentiated Sulfonamide Antimicrobial (Systemic Drug)

Uses / Indications

Although sulfadiazine/trimethoprim is only FDA approved for use in dogs and horses, this drug is used to treat infections caused by susceptible bacteria and parasitic organisms in various species.

Sulfadiazine/trimethoprim is commonly used in horses because it is 1 of a limited number of safe oral options. Although use in dogs is more limited because of concerns about adverse effects and availability of other antimicrobial options, this drug is a potential choice for treatment of various infections (eg, cystitis, prostatitis). This drug is also sometimes used for treatment of atypical pathogens (eg, Nocardia spp). Prophylactic use of sulfadiazine/trimethoprim reduced morbidity in dogs receiving doxorubicin.¹

The World Health Organization (WHO) has designated sulfamethoxazole/trimethoprim as a Highly Important antimicrobial for human medicine.² The Office International des Epizooties (OIE) Antimicrobial Classification has designated sulfadiazine/trimethoprim as a Veterinary Critically Important antimicrobial.³

Contraindications / Precautions / Warnings

The veterinary manufacturer states that sulfadiazine/trimethoprim should not be used in dogs or horses with marked liver parenchymal damage, impaired hepatic function, blood dyscrasias, or a history of sulfonamide or trimethoprim sensitivity. Sulfadiazine/trimethoprim is not for use in horses (or FDA approved for other animals) intended for food.

Doberman pinschers, Samoyeds, and miniature schnauzers appear to be more susceptible to sulfonamide-induced polysystemic immune complex disease¹³; use sulfa-/trimethoprim with caution in these breeds.

Sulfa-/trimethoprim should be used with caution in patients with pre-existing hepatic or renal disease or folate deficiency. In animals with moderate to severe renal dysfunction, consider dosage reduction; avoid products containing sulfadiazine.

Sulfadiazine has potential for crystallization in the urine, so use should be avoided in dogs with uroliths, at increased risk for developing uroliths, with highly concentrated urine (from dehydration), or with acidic urine.

The UK label states that horses receiving sulfadiazine/trimethoprim may develop potentially fatal acute diarrhea. Discontinue antimicrobial therapy if acute diarrhea or persistent changes in fecal consistency are observed, and initiate appropriate treatment. The UK label also states that this antibiotic should not be administered to horses with drug-induced cardiac arrhythmias (eg, anesthetic and sedative agents) and that it should not be given IV concurrently or with previous administration of CNS depressants (eg, anesthetic agents, phenothiazines).

In humans, sulfamethoxazole/trimethoprim is contraindicated in patients younger than 2 months of age, with known hypersensitivity to either drug component, with marked hepatic or renal impairment, and with megaloblastic anemia due to folate deficiency.

Adverse Effects

Adverse effects noted in dogs include keratoconjunctivitis sicca (KCS; which may be irreversible), acute neutrophilic hepatitis with icterus, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swelling, polydipsia, polyuria, and cholestasis. Potentiated sulfonamides may cause clinical hypothyroidism in dogs, particularly with extended therapy. Acute hypersensitivity reactions manifesting as type I (ie, anaphylaxis) or type III (ie, formation of antigen:antibody complexes) reactions can be seen. Hypersensitivity reactions appear to be more common in large-breed dogs. Doberman pinschers, Samoyeds, and miniature schnauzers may be more susceptible to hypersensitivity reactions than other breeds.¹³ Other hematologic effects (eg, anemia, agranulocytosis) are possible but are rare. Sulfa-/trimethoprim has rarely caused an idiosyncratic, moderate to massive hepatic necrosis in dogs.¹⁴ Use of sulfa-/trimethoprim may increase the risk for developing acute pancreatitis,¹³ but cause and effect have not been definitively shown.

Adverse effects noted in cats may include anorexia, leukopenia, and anemia.

Regurgitation may occur in birds.

In horses, transient pruritus has been noted after IV injection. Oral therapy has resulted in dose-related diarrhea, but incidence is relatively low. Previous administration of potentiated sulfonamides has been implicated in increasing the mortality rate associated with severe diarrhea. If the 48% injectable product is administered IM or SC, or if it extravasates after IV administration, swelling, pain, and minor tissue damage may result. Hypersensitivity reactions, neurologic effects (eg, gait alterations, behavior changes), cutaneous vasculitis, and hematologic effects (eg, anemia, thrombocytopenia, leukopenia) may also be seen.¹⁵ In experimental models, trimethoprim inhibited equine voltage-gated K+ channel K(v)11.1, suggesting that trimethoprim could induce repolarization disorders in horses^16,17; validation with in vivo studies are needed.

Sulfonamides (and their metabolites) can precipitate in the urine, particularly when given at high dosages for prolonged periods. Acidic or highly concentrated urine may also contribute to increased risk for crystalluria, hematuria, and renal tubule obstruction.

Sulfamethoxazole/trimethoprim can markedly reduce tear production in rabbits,¹⁸ but sulfadiazine/trimethoprim had no effect in horses.¹⁹

Reproductive / Nursing Safety

Trimethoprim and sulfonamides cross the placenta. Safety of sulfa-/trimethoprim has not been clearly established in pregnant animals. Reports of teratogenicity (eg, cleft palate, fetal loss) have been reported in rats and rabbits. Studies in male animals have not demonstrated reduced reproductive performance. First trimester exposure in humans has been associated with increased risk for congenital malformations.

Trimethoprim and sulfonamides are distributed into milk. Use sulfa-/trimethoprim products in nursing animals with caution. Sulfamethoxazole/trimethoprim is not recommended for human use during the nursing period, as sulfonamides are excreted into milk and may cause kernicterus. Premature infants and infants with hyperbilirubinemia or G-6-PD deficiency are also at risk for adverse effects.

Overdose / Acute Toxicity

Manifestations of an acute overdose can include clinical signs of GI distress (eg, nausea, vomiting, diarrhea), CNS toxicity (eg, depression,), facial swelling, bone marrow depression, and increased serum aminotransferase (ie, ALT, AST) activity. Oral overdoses can be treated by emptying the stomach (following typical protocols) and initiating supportive therapy based on clinical signs. Acidification of the urine may increase the renal elimination of trimethoprim but could also cause sulfonamide crystalluria, particularly with sulfadiazine-containing products. CBC and other laboratory parameters should be monitored as necessary. Severe bone marrow suppression associated with chronic overdoses can be treated with folinic acid (leucovorin). Peritoneal dialysis is not effective in removing trimethoprim or sulfonamides from circulation.

For patients that have experienced or are suspected to have experienced an overdose, consultation with a 24-hour poison consultation center specializing in providing veterinary-specific information is recommended. For general information related to overdose and toxin exposures, as well as contact information for poison control centers, refer to Appendix.

Drug Interactions

In humans, trimethoprim may be a substrate of p-glycoprotein, sulfamethoxazole is a substrate of the CYP2C family, and both trimethoprim and sulfamethoxazole may inhibit CYP2C enzymes. The following drug interactions have either been reported or are theoretical in humans or animals receiving sulfa-/trimethoprim and may be of significance in veterinary patients. Unless otherwise noted, use together is not necessarily contraindicated, but weigh the potential risks and perform additional monitoring when appropriate.

• AMANTADINE: A human patient developed toxic delirium while receiving amantadine in conjunction with sulfamethoxazole/trimethoprim.²⁰
• ANESTHETIC AGENTS: Concurrent IV administration is contraindicated. Ester-type local anesthetics (eg, procaine, tetracaine) may locally inhibit sulfonamide effects.^21,22
• ANGIOTENSIN II-RECEPTOR BLOCKERS (ARBs; eg, telmisartan): May increase the risk for hyperkalemia when used with potassium-sparing drugs
• ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEIs; eg, benazepril, enalapril): May increase the risk for hyperkalemia when used with potassium-sparing drugs
• ANTACIDS: Concurrent administration may decrease sulfonamide bioavailability.
• AZATHIOPRINE: Increased risk for myelosuppression
• CYCLOSPORINE: Sulfa-/trimethoprim may increase the risk of nephrotoxicity.
• DETOMIDINE: Concurrent use has resulted in fatal arrhythmias in horses.¹⁷
• DIGOXIN: Sulfa-/trimethoprim may increase digoxin levels.
• DIURETICS, THIAZIDE: May increase the risk for thrombocytopenia
• HYPOGLYCEMIC AGENTS, ORAL (eg, glipizide, metformin): Sulfa-/trimethoprim may potentiate hypoglycemic effects.
• METHENAMINE: May form an insoluble precipitate in the urine
• METHOTREXATE: Sulfa-/trimethoprim may displace from plasma proteins and increase risk for toxic effects; it can also interfere with MTX assays (competitive protein binding technique, but not when measured by radioimmunoassay).
• PHENOTHIAZINES (eg, acepromazine, promethazine): Concurrent administration is contraindicated.
• PHENYTOIN: Sulfa-/trimethoprim may increase half-life.
• POTASSIUM SUPPLEMENTS: Increased risk for hyperkalemia
• PROCAINAMIDE: Sulfa-/trimethoprim may increase levels of procainamide and its active metabolite.
• PYRIMETHAMINE: May increase the risk of megaloblastic anemia and myelosuppression
• RIFAMPIN: May reduce serum concentrations of both trimethoprim and sulfonamide
• SPIRONOLACTONE: May increase the risk for hyperkalemia when used with potassium-sparing drugs
• TRICYCLIC ANTIDEPRESSANTS (TCAs; eg, amitriptyline, clomipramine): Sulfa-/trimethoprim may decrease efficacy.
• WARFARIN: Sulfa-/trimethoprim may prolong prothrombin time and INR

Laboratory Considerations

• When using the Jaffe alkaline picrate reaction assay for creatinine determination, sulfa-/trimethoprim may cause an overestimation of ≈10%.

• Sulfonamides may give false-positive results for urine glucose determinations when using the Benedict’s method.

Dosages

NOTE: There is significant controversy regarding the frequency of administration of these drugs. See Pharmacokinetics for more information. Unless otherwise noted, doses are for combined sulfa-/trimethoprim. See Monitoring if treatment is expected to be longer than 7 days.

DOGS:

Susceptible bacterial infections:

• Labeled indications (…for sensitive organisms alone or as an adjunct to surgery or debridement with associated infection; acute urinary tract infections; acute bacterial complications of distemper; acute respiratory tract infections; acute alimentary tract infections; wound infections; abscesses); (FDA approved): 30 mg/kg PO once daily. Alternatively, especially in severe infections, the initial dose may be followed by 15 mg/kg every 12 hours.²³
• Superficial bacterial folliculitis (extra-label): 15 – 30 mg/kg PO twice daily.²⁴ Potentiated sulfonamides (ie, sulfa-/trimethoprim, sulfadimethoxine/ormetoprim) are first-tier drugs only if regional susceptibility of Staphylococcus pseudintermedius is known.
• Bacterial cystitis (extra-label): Potentiated sulfonamides (ie, sulfa-/trimethoprim, sulfadimethoxine/ormetoprim) are first-tier drugs only if regional pathogen susceptibility patterns are known.²⁵
  • Uncomplicated UTI: 15 mg/kg PO every 12 hours. Treatment may be as short as 3 days.^25,26
  • Complicated UTI: 15 – 30 mg/kg PO every 12 hours.²⁵
• Parasitic diseases (all are extra-label):
  • Neosporosis: Sulfadiazine/trimethoprim 15 – 20 mg/kg PO every 12 hours for 4 weeks in combination with pyrimethamine 1 mg/kg PO once daily for 4 weeks. If observable clinical improvement is slow, treatment should be extended beyond the recommended 4 weeks until 2 weeks after clinical signs have plateaued. All littermates of affected puppies should be treated regardless of clinical signs. Alternative treatment is clindamycin 12.5 – 25 mg/kg PO or IM every 12 hours for 4 weeks.²⁷ NOTE: There is no approved or curative treatment for canine neosporosis. Arrestment of clinical disease is best achieved when treatment is initiated before the occurrence of contracture or paralysis.
  • Toxoplasmosis: Sulfa-/trimethoprim 15 mg/kg PO every 12 hours for 4 weeks can be used. Supportive care should be provided as needed.²⁷ There is no approved treatment for toxoplasmosis in dogs.
  • Pneumocystosis (Pneumocystis jiroveci): 15 mg/kg PO every 8 hours for 3 weeks or 30 mg/kg PO every 12 hours for 3 weeks
  • American canine hepatozoonosis (Hepatozoon americanum): Triple-combination therapy (TCP) consists of sulfadiazine/trimethoprim 15 mg/kg PO every 12 hours for 14 days, clindamycin 10 mg/kg PO every 8 hours for 14 days, and pyrimethamine 0.25 mg/kg PO every 24 hours for 14 days or ponazuril 10 mg/kg PO every 12 hours for 14 days. Prolonged therapy consists of decoquinate 10 – 20 mg/kg mixed in food twice daily; treatment is continued for 2 years. If relapse occurs, either ponazuril or TCP should be administered again for 14 days, followed by long-term decoquinate therapy.²⁸ NOTE: No treatment is effective in eliminating H americanum in infected dogs. Treatment can increase survival time, improve quality of life, and decrease the number and severity of clinical relapses. Supportive care can ensure hydration, and NSAIDs can assist with pain control.

CATS:

Contraindications / Precautions / Warnings

The veterinary manufacturer states that sulfadiazine/trimethoprim should not be used in dogs or horses with marked liver parenchymal damage, impaired hepatic function, blood dyscrasias, or a history of sulfonamide or trimethoprim sensitivity. Sulfadiazine/trimethoprim is not for use in horses (or FDA approved for other animals) intended for food.

Doberman pinschers, Samoyeds, and miniature schnauzers appear to be more susceptible to sulfonamide-induced polysystemic immune complex disease¹³; use sulfa-/trimethoprim with caution in these breeds.

Sulfa-/trimethoprim should be used with caution in patients with pre-existing hepatic or renal disease or folate deficiency. In animals with moderate to severe renal dysfunction, consider dosage reduction; avoid products containing sulfadiazine.

Sulfadiazine has potential for crystallization in the urine, so use should be avoided in dogs with uroliths, at increased risk for developing uroliths, with highly concentrated urine (from dehydration), or with acidic urine.

The UK label states that horses receiving sulfadiazine/trimethoprim may develop potentially fatal acute diarrhea. Discontinue antimicrobial therapy if acute diarrhea or persistent changes in fecal consistency are observed, and initiate appropriate treatment. The UK label also states that this antibiotic should not be administered to horses with drug-induced cardiac arrhythmias (eg, anesthetic and sedative agents) and that it should not be given IV concurrently or with previous administration of CNS depressants (eg, anesthetic agents, phenothiazines).

In humans, sulfamethoxazole/trimethoprim is contraindicated in patients younger than 2 months of age, with known hypersensitivity to either drug component, with marked hepatic or renal impairment, and with megaloblastic anemia due to folate deficiency.

Adverse Effects

Adverse effects noted in dogs include keratoconjunctivitis sicca (KCS; which may be irreversible), acute neutrophilic hepatitis with icterus, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swelling, polydipsia, polyuria, and cholestasis. Potentiated sulfonamides may cause clinical hypothyroidism in dogs, particularly with extended therapy. Acute hypersensitivity reactions manifesting as type I (ie, anaphylaxis) or type III (ie, formation of antigen:antibody complexes) reactions can be seen. Hypersensitivity reactions appear to be more common in large-breed dogs. Doberman pinschers, Samoyeds, and miniature schnauzers may be more susceptible to hypersensitivity reactions than other breeds.¹³ Other hematologic effects (eg, anemia, agranulocytosis) are possible but are rare. Sulfa-/trimethoprim has rarely caused an idiosyncratic, moderate to massive hepatic necrosis in dogs.¹⁴ Use of sulfa-/trimethoprim may increase the risk for developing acute pancreatitis,¹³ but cause and effect have not been definitively shown.

Adverse effects noted in cats may include anorexia, leukopenia, and anemia.

Regurgitation may occur in birds.

In horses, transient pruritus has been noted after IV injection. Oral therapy has resulted in dose-related diarrhea, but incidence is relatively low. Previous administration of potentiated sulfonamides has been implicated in increasing the mortality rate associated with severe diarrhea. If the 48% injectable product is administered IM or SC, or if it extravasates after IV administration, swelling, pain, and minor tissue damage may result. Hypersensitivity reactions, neurologic effects (eg, gait alterations, behavior changes), cutaneous vasculitis, and hematologic effects (eg, anemia, thrombocytopenia, leukopenia) may also be seen.¹⁵ In experimental models, trimethoprim inhibited equine voltage-gated K+ channel K(v)11.1, suggesting that trimethoprim could induce repolarization disorders in horses^16,17; validation with in vivo studies are needed.

Sulfonamides (and their metabolites) can precipitate in the urine, particularly when given at high dosages for prolonged periods. Acidic or highly concentrated urine may also contribute to increased risk for crystalluria, hematuria, and renal tubule obstruction.

Sulfamethoxazole/trimethoprim can markedly reduce tear production in rabbits,¹⁸ but sulfadiazine/trimethoprim had no effect in horses.¹⁹

Reproductive / Nursing Safety

Trimethoprim and sulfonamides cross the placenta. Safety of sulfa-/trimethoprim has not been clearly established in pregnant animals. Reports of teratogenicity (eg, cleft palate, fetal loss) have been reported in rats and rabbits. Studies in male animals have not demonstrated reduced reproductive performance. First trimester exposure in humans has been associated with increased risk for congenital malformations.

Trimethoprim and sulfonamides are distributed into milk. Use sulfa-/trimethoprim products in nursing animals with caution. Sulfamethoxazole/trimethoprim is not recommended for human use during the nursing period, as sulfonamides are excreted into milk and may cause kernicterus. Premature infants and infants with hyperbilirubinemia or G-6-PD deficiency are also at risk for adverse effects.

Overdose / Acute Toxicity

Manifestations of an acute overdose can include clinical signs of GI distress (eg, nausea, vomiting, diarrhea), CNS toxicity (eg, depression,), facial swelling, bone marrow depression, and increased serum aminotransferase (ie, ALT, AST) activity. Oral overdoses can be treated by emptying the stomach (following typical protocols) and initiating supportive therapy based on clinical signs. Acidification of the urine may increase the renal elimination of trimethoprim but could also cause sulfonamide crystalluria, particularly with sulfadiazine-containing products. CBC and other laboratory parameters should be monitored as necessary. Severe bone marrow suppression associated with chronic overdoses can be treated with folinic acid (leucovorin). Peritoneal dialysis is not effective in removing trimethoprim or sulfonamides from circulation.

For patients that have experienced or are suspected to have experienced an overdose, consultation with a 24-hour poison consultation center specializing in providing veterinary-specific information is recommended. For general information related to overdose and toxin exposures, as well as contact information for poison control centers, refer to Appendix.

Drug Interactions

In humans, trimethoprim may be a substrate of p-glycoprotein, sulfamethoxazole is a substrate of the CYP2C family, and both trimethoprim and sulfamethoxazole may inhibit CYP2C enzymes. The following drug interactions have either been reported or are theoretical in humans or animals receiving sulfa-/trimethoprim and may be of significance in veterinary patients. Unless otherwise noted, use together is not necessarily contraindicated, but weigh the potential risks and perform additional monitoring when appropriate.

• AMANTADINE: A human patient developed toxic delirium while receiving amantadine in conjunction with sulfamethoxazole/trimethoprim.²⁰
• ANESTHETIC AGENTS: Concurrent IV administration is contraindicated. Ester-type local anesthetics (eg, procaine, tetracaine) may locally inhibit sulfonamide effects.^21,22
• ANGIOTENSIN II-RECEPTOR BLOCKERS (ARBs; eg, telmisartan): May increase the risk for hyperkalemia when used with potassium-sparing drugs
• ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEIs; eg, benazepril, enalapril): May increase the risk for hyperkalemia when used with potassium-sparing drugs
• ANTACIDS: Concurrent administration may decrease sulfonamide bioavailability.
• AZATHIOPRINE: Increased risk for myelosuppression
• CYCLOSPORINE: Sulfa-/trimethoprim may increase the risk of nephrotoxicity.
• DETOMIDINE: Concurrent use has resulted in fatal arrhythmias in horses.¹⁷
• DIGOXIN: Sulfa-/trimethoprim may increase digoxin levels.
• DIURETICS, THIAZIDE: May increase the risk for thrombocytopenia
• HYPOGLYCEMIC AGENTS, ORAL (eg, glipizide, metformin): Sulfa-/trimethoprim may potentiate hypoglycemic effects.
• METHENAMINE: May form an insoluble precipitate in the urine
• METHOTREXATE: Sulfa-/trimethoprim may displace from plasma proteins and increase risk for toxic effects; it can also interfere with MTX assays (competitive protein binding technique, but not when measured by radioimmunoassay).
• PHENOTHIAZINES (eg, acepromazine, promethazine): Concurrent administration is contraindicated.
• PHENYTOIN: Sulfa-/trimethoprim may increase half-life.
• POTASSIUM SUPPLEMENTS: Increased risk for hyperkalemia
• PROCAINAMIDE: Sulfa-/trimethoprim may increase levels of procainamide and its active metabolite.
• PYRIMETHAMINE: May increase the risk of megaloblastic anemia and myelosuppression
• RIFAMPIN: May reduce serum concentrations of both trimethoprim and sulfonamide
• SPIRONOLACTONE: May increase the risk for hyperkalemia when used with potassium-sparing drugs
• TRICYCLIC ANTIDEPRESSANTS (TCAs; eg, amitriptyline, clomipramine): Sulfa-/trimethoprim may decrease efficacy.
• WARFARIN: Sulfa-/trimethoprim may prolong prothrombin time and INR

Laboratory Considerations

• When using the Jaffe alkaline picrate reaction assay for creatinine determination, sulfa-/trimethoprim may cause an overestimation of ≈10%.

• Sulfonamides may give false-positive results for urine glucose determinations when using the Benedict’s method.

Dosages

NOTE: There is significant controversy regarding the frequency of administration of these drugs. See Pharmacokinetics for more information. Unless otherwise noted, doses are for combined sulfa-/trimethoprim. See Monitoring if treatment is expected to be longer than 7 days.

DOGS:

Susceptible bacterial infections:

• Labeled indications (…for sensitive organisms alone or as an adjunct to surgery or debridement with associated infection; acute urinary tract infections; acute bacterial complications of distemper; acute respiratory tract infections; acute alimentary tract infections; wound infections; abscesses); (FDA approved): 30 mg/kg PO once daily. Alternatively, especially in severe infections, the initial dose may be followed by 15 mg/kg every 12 hours.²³
• Superficial bacterial folliculitis (extra-label): 15 – 30 mg/kg PO twice daily.²⁴ Potentiated sulfonamides (ie, sulfa-/trimethoprim, sulfadimethoxine/ormetoprim) are first-tier drugs only if regional susceptibility of Staphylococcus pseudintermedius is known.
• Bacterial cystitis (extra-label): Potentiated sulfonamides (ie, sulfa-/trimethoprim, sulfadimethoxine/ormetoprim) are first-tier drugs only if regional pathogen susceptibility patterns are known.²⁵
  • Uncomplicated UTI: 15 mg/kg PO every 12 hours. Treatment may be as short as 3 days.^25,26
  • Complicated UTI: 15 – 30 mg/kg PO every 12 hours.²⁵
• Parasitic diseases (all are extra-label):
  • Neosporosis: Sulfadiazine/trimethoprim 15 – 20 mg/kg PO every 12 hours for 4 weeks in combination with pyrimethamine 1 mg/kg PO once daily for 4 weeks. If observable clinical improvement is slow, treatment should be extended beyond the recommended 4 weeks until 2 weeks after clinical signs have plateaued. All littermates of affected puppies should be treated regardless of clinical signs. Alternative treatment is clindamycin 12.5 – 25 mg/kg PO or IM every 12 hours for 4 weeks.²⁷ NOTE: There is no approved or curative treatment for canine neosporosis. Arrestment of clinical disease is best achieved when treatment is initiated before the occurrence of contracture or paralysis.
  • Toxoplasmosis: Sulfa-/trimethoprim 15 mg/kg PO every 12 hours for 4 weeks can be used. Supportive care should be provided as needed.²⁷ There is no approved treatment for toxoplasmosis in dogs.
  • Pneumocystosis (Pneumocystis jiroveci): 15 mg/kg PO every 8 hours for 3 weeks or 30 mg/kg PO every 12 hours for 3 weeks
  • American canine hepatozoonosis (Hepatozoon americanum): Triple-combination therapy (TCP) consists of sulfadiazine/trimethoprim 15 mg/kg PO every 12 hours for 14 days, clindamycin 10 mg/kg PO every 8 hours for 14 days, and pyrimethamine 0.25 mg/kg PO every 24 hours for 14 days or ponazuril 10 mg/kg PO every 12 hours for 14 days. Prolonged therapy consists of decoquinate 10 – 20 mg/kg mixed in food twice daily; treatment is continued for 2 years. If relapse occurs, either ponazuril or TCP should be administered again for 14 days, followed by long-term decoquinate therapy.²⁸ NOTE: No treatment is effective in eliminating H americanum in infected dogs. Treatment can increase survival time, improve quality of life, and decrease the number and severity of clinical relapses. Supportive care can ensure hydration, and NSAIDs can assist with pain control.

Susceptible bacterial infections:

• Bacterial cystitis (extra-label): Potentiated sulfonamides (ie, sulfa-/trimethoprim, sulfadimethoxine/ormetoprim) are first-tier drugs only if regional pathogen susceptibility patterns are known.²⁵
  • Uncomplicated UTI: 15 mg/kg PO every 12 hours. Treatment may be as short as 3 days.^25,26
  • Complicated UTI: 15 – 30 mg/kg PO every 12 hours.²⁵
• Parasitic diseases:
  • Toxoplasmosis (extra-label): Sulfa-/trimethoprim 15 mg/kg PO every 12 hours for 4 weeks can be used. Supportive care should be provided as needed.²⁷ NOTE: There is no approved treatment for toxoplasmosis in cats.

Storage / Stability

Unless otherwise instructed by the manufacturer, sulfa-/trimethoprim products should be stored at room temperature of 20°C to 25°C (68°F-77°F) in tight containers and protected from freezing. Shake suspensions well before use.