Co-Trimoxazole ( Trimethoprim–Sulfamethoxazole)

Brand names Generic

Medication error None reported potential

Contraindications Contraindications: In those (1) with known hypersensitivity to sulfa drug, trimethoprim, and warnings or any component of the formulation; (2) with documented megaloblastic anemia due to folate deficiency; (3) <2 months of age*; (4) who are pregnant or breastfeeding because sulfonamides are excreted in the milk and may cause in the ; and (5) with a history of immune with sulfonamide use.(2) *Except for Pneumocystis jirovecii prophylaxis in >4 weeks old who were born to HIV-infected mothers.(3) Warnings: Fatalities have occurred due to severe dermatologic reactions (i.e., Stevens- Johnson syndrome and toxic epidermal necrolysis). Sulfonamides should be discontinued at the first appearance of skin rash.(2) Fulminant hepatic necrosis and a variety of dyscrasias (e.g., agranulocytosis, aplastic anemia) have been reported.(2) Dose-dependent hemolysis may occur in patients with G6PD-deficiency.(2) (See Rare Adverse Effects in the Comments Section.) Use caution in use in patients at risk for folate deficiency.(2) Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tract that have been reported.(2) Prolonged use may cause superinfection and/or Clostridium difficile-associated diarrhea (CDAD), which has been reported and may range in severity from mild diarrhea to fatal colitis.(2) If CDAD is suspected or confirmed, appropriate fluid and electrolyte manage- ment, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.(2)

Infusion-related Pain, local irritation, inflammation, and rarely thrombophlebitis may occur.(2) cautions

Dosage Dosage is based on trimethoprim component. Neonates: Not recommended for those <2 months of age because sulfonamides may cause kernicterus by displacing from plasma protein-binding sites(2); however, may be used for Pneumocystis jirovecii in infants >4 weeks of age with HIV infection or those born to HIV-infected mothers.(3) Infants and children Mild-to-moderate infections: 6–12 mg/kg/day divided q 12 hr(3) Severe infections: 6–12 mg/kg/day divided q 6–12 hr.(2,3) Give up to 14 days for severe urinary tract infection and 5 days for shigellosis.(2) Meningitis (not first-line; alternative ): 10–20 mg/kg/day divided q 6–12 hr has been used.(4-7) Pneumocystis jirovecii pneumonia: 15–20 mg/kg/day divided q 6–8 hr for 14–21 days(2,19)

Dosage adjustment If CrCl is 15–30 mL/min, the manufacturer recommends to give 50% the normal dose.(2) in organ dysfunction Not recommended by the manufacturer if CrCl is <15 mL/min.(2) Another reference states if GFR 30–50, give 5–7.5 mg/kg q 8 hr; if GFR 10–29, give 5–10 mg/kg q 12 hr; not recommended if GRF <10, but if required give 5–10 mg/kg q 24 hr.(10)

Maximum dosage 20 mg/kg/day(2)  224 Co-Trimoxazole ( Trimethoprim–Sulfamethoxazole)

Additives Contains sodium metabisulfite, propylene glycol, ethyl alcohol, and benzyl alcohol.(2,13) (See Appendix C for specific information about sulfite hypersensitivity, benzyl alcohol, and propylene glycol toxicity.)

Suitable diluents D5W(2,13)

Maximum 5 mL of the 80/16 mg/mL trimethoprim–sulfamethoxazole concentrate in 125 mL of concentration D5W,(2,13) or 5 mL of concentrate in 75 mL of D5W in fluid-restricted patients(2,13)

Preparation and Stability: Do not refrigerate concentrate for injection.(2,13) 5 mL of the 80/16 mg/mL tri- delivery methoprim–sulfamethoxazole concentrate in 125 mL D5W is stable for 6 hours(2,13); 5 mL concentrate in 100 mL D5W is stable for 4 hours(2,13); 5 mL concentrate in 75 mL D5W is stable for 2 hours at room temperature.(2,13) Check for precipitation before use.(2,13) Compatibility: See Appendix D for PN compatibility information.(14)

IV push Not recommended(2,13)

Intermittent infusion Over 60–90 minutes(2,13)

Continuous infusion Not used

Other routes of None administration

Comments Significant adverse effects: Stevens-Johnson syndrome and toxic epidermal necrolysis may occur with sulfonamide therapy.(2) 1–3 days before the appearance of a rash, patients develop a prodrome of fever, stinging eyes, and sore throat.(15) The initial lesions are erythematous to purpuric macules, which first appear on the trunk and spreading to the face and proximal extremities.(15) Lesions may then progress to full-thickness necrosis with flaccid blisters. Most patients (90%) develop buccal, oral, and genital mucosal involve- ment with erythema and erosions.(15) Sulfonamide should be discontinued immediately at first sign of rash.(2) Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, , methemoglobinemia, and eosinophilia have been reported.(2) Hemolysis has been reported in individuals with G6PD deficiency.(2) Hepatitis, including cholestatic , hepatic necrosis, and failure, which may progress to transplantation.(2,16,17) Rare adverse effects: Trimethoprim can cause hyperkalemia.(2) This can occur with both large and standard dosages of trimethoprim but generally occurs in those with renal impairment, hypoaldosteronism, or concurrent known to impair renal potas- sium excretion.(18) Management may require discontinuation or dose adjustment of trim- ethoprim, volume repletion with isotonic fluids, and administration of specific to hyperkalemia.(18) Monitoring: CBC, serum potassium, serum transaminases, and bilirubin. time should be monitored in those on .(2) Drug interactions: Trimethoprim is 45% and sulfamethoxazole is 70% bound to plasma protein.(2) Because co-trimoxazole is associated with numerous drug interactions, consult appropriate resources for dosing recommendations before combining any drug with co-trimoxazole. Laboratory interference: The presence of trimethoprim and sulfamethoxazole may interfere with the Jaffe assay for creatinine, resulting in about 10% overestimation.(2) The trimethoprim component can interfere with determination of serum methotrexate concentrations.(2) This occurs if a bacterial dihydrofolate reductase is used as the bind- ing protein source in the competitive binding protein technique but does not occur if a radioimmunoassay is used.(2)  225