Bactrim IV (Trimethoprim and Sulfamethoxazole) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

In elderly patients concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported.

It has been reported that Bactrim may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when Bactrim is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.

Bactrim may inhibit the hepatic metabolism of phenytoin. Bactrim, given at a common clinical dosage, increased the phenytoin half-life by 39% and decreased the phenytoin metabolic clearance rate by 27%. When administering these drugs concurrently, one should be alert for possible excessive phenytoin effect.

Sulfonamides can also displace methotrexate from plasma protein binding sites, thus increasing free methotrexate concentrations.

OVERDOSE

Acute: Since there has been no extensive experience in humans with single doses of Bactrim IV Infusion in excess of 25 mL (400 mg trimethoprim and 2000 mg sulfamethoxazole), the maximum tolerated dose in humans is unknown. Signs and symptoms of overdosage reported with sulfonamides include anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness and unconsciousness. Pyrexia, hematuria and crystalluria may be noted. Blood dyscrasias and jaundice are potential late manifestations of overdosage.

Signs of acute overdosage with trimethoprim include nausea, vomiting, dizziness, headache, mental depression, confusion and bone marrow depression.

General principles of treatment include the administration of intraveneous fluids if urine output is low and renal function is normal. Acidification of the urine will increase renal elimination of trimethoprim. The patient should be monitored with blood counts and appropriate blood chemistries, including electrolytes. If a significant blood dyscrasia or jaundice occurs, specific therapy should be instituted for these complications. Peritoneal dialysis is not effective and hemodialysis is only moderately effective in eliminating trimethoprim and sulfamethoxazole.

Chronic: Use of Bactrim IV Infusion at high doses and/or for extended periods of time may cause bone marrow depression manifested as thrombocytopenia, leukopenia and/or megaloblastic anemia. If signs of bone marrow depression occur, the patient should be given leucovorin 5 to 15 mg daily until normal hematopoiesis is restored.

Animal Toxicity: The LD ₅₀ of Bactrim IV Infusion in mice is 700 mg/kg or 7.3 mL/kg; in rats and rabbits the LD ₅₀ is >500 mg/kg or >5.2 mL/kg. The vehicle produced the same LD ₅₀ in each of these species as the active drug.

The signs and symptoms noted in mice, rats and rabbits with Bactrim IV Infusion or its vehicle at the high IV doses used in acute toxicity studies included ataxia, decreased motor activity, loss of righting reflex, tremors or convulsions, and/or respiratory depression.

CONTRAINDICATIONS

Bactrim is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides and in patients with documented megaloblastic anemia due to folate deficiency. Bactrim is also contraindicated in pregnant patients and nursing mothers, because sulfonamides pass the placenta and are excreted in the milk and may cause kernicterus. Bactrim is contraindicated in infants less than 2 months of age.

REFERENCES

1. Grose WE, Bodey GP, Loo TL. Clinical Pharmacology of Intravenously Administered Trimethoprim-Sulfamethoxazole. Antimicrob Agents Chemother. Mar 1979;15:447-451.
2. Siber GR, Gorham C, Durbin W, Lesko L, Levin MJ. Pharmacology of Intravenous Trimethoprim-Sulfamethoxazole in Children and Adults. Current Chemotherapy and Infectious Diseases. American Society for Microbiology, Washington, D.C., 1980, Vol. 1, pp. 691-692.
3. Bauer AW, Kirby WMM, Sherris JC, Turck M. Antibiotic Susceptibility Testing by a Standardized Single Disk Method. Am J Clin Pathol. Apr 1966;45:493-496.
4. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disc Susceptibility Test. 771 East Lancaster Avenue, Villanova, Pennsylvania 19085: Approved Standard ASM-2.
5. Brumfitt W, Pursell R. Trimethoprim/Sulfamethoxazole in the Treatment of Bacteriuria in Women. J Infect Dis. Nov 1973;128 (Suppl):S657-S663.
6. Winston DJ, Lau WK, Gale RP, Young LS. Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis carinii pneumonia. Ann Intern Med. June 1980;92:762-769.