Ativet

Alone, sulfonamides are bacteriostatic agents and trimethoprim is bactericidal, but when used in combination, the potentiated sulfas are bactericidal. Potentiated sulfas sequentially inhibit enzymes in the folic acid pathway, inhibiting bacterial thymidine synthesis. The sulfonamide blocks the conversion of para-aminobenzoic acid (PABA) to dihydrofolic acid (DFA), and trimethoprim blocks the conversion of DFA to tetrahydrofolic acid by inhibiting dihydrofolate reductase. Infected tissue and cellular debris can inhibit the activity of trimethoprim/sulfa by secreting PABA and thymidine.

AMANTADINE: A human patient developed toxic delirium when receiving amantadine with TMP/sulfa
ANTACIDS: May decrease the bioavailability of sulfonamides if administered concurrently
CYCLOSPORINE: TMP/sulfa may increase the risk of nephrotoxicity
DIGOXIN: TMP/sulfa may increase digoxin levels
DIURETICS, THIAZIDE: May increase risk for thrombocytopenia
HYPOGLYCEMIC AGENTS, ORAL: TMP/sulfa may potentiate effects
METHOTREXATE: TMP/sulfa may displace from plasma proteins and
increase risk for toxic effects; it can also interfere with MTX assays
(competitive protein binding technique)
PHENYTOIN: TMP/sulfa may increase half-life
TRICYCLIC ANTIDEPRESSANTS: TMP/sulfa may decrease efficacy
WARFARIN: TMP/sulfa may prolong INR/PT

keratoconjunctivitis sicca (which may be irreversible), acute neutrophilic hepatitis with icterus, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swelling, polydipsia, polyuria and cholestasis.

Manifestations of an acute overdosage can include clinical signs of GI distress (nausea, vomiting, diarrhea), CNS toxicity (depression, headache, and confusion), facial swelling, bone marrow depression and increases in serum aminotransferases. Oral overdoses can be treated by emptying the stomach, (following usual protocols), and initiating symptomatic and supportive therapy. 

Acidification of the urine may increase the renal elimination of trimethoprim, but could also cause sulfonamide crystalluria, particularly with sulfadiazine containing products. Complete blood counts (and other laboratory parameters) should be monitored as necessary. Bone marrow suppression associated with chronic overdoses may be treated with folinic acid (leucovorin) if severe. Peritoneal dialysis is not effective in removing TMP or sulfas from the circulation.

Safety of trimethoprim/sulfa has not been clearly established in pregnant animals. Reports of teratogenicity (cleft palate) have been reported. Studies thus far in male animals have not demonstrated any decreases in reproductive performance

Store below 30° C and dry place, protected from light. Keep all medicines out of reach of children