Trimethoprim and sulfadiazine: adverse effects of long-term administration in dogs

A trimethoprim-sulfonamide combination was administered to dogs for eight weeks at the therapeutic dose rate (15 mg/kg twice daily) and at three times the therapeutic dose rate (recommended maximum duration of therapy is two weeks). The lower dose produced no adverse effects, but the high dose caused decreases in packed cell volume, mean cell volume, and mean cell haemoglobin, and increases in blood urea nitrogen, serum creatinine, and plasma protein concentration. Reduced folate levels were decreased, indicating impaired folate metabolism. One dog of initial low folate status became pancytopenic, but the other dogs in the group remained clinically normal. All changes were quickly reversible on withdrawal of the drug. It is concluded that use of the drug as recommended affords a wide margin of safety. Adverse effects may appear if the drug is given at high levels for a prolonged period, especially when the pretreatment folate status of the animal is poor..