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ANTIINFECTIVES FOR SYSTEMIC USE › ANTIBACTERIALS FOR SYSTEMIC USE › COMBINATIONS OF ANTIBACTERIALS › Combinations of antibacterials
sulfonamides, combinations with other antibacterials (excl. trimethoprim)
J01RA02
Forms & Strengths
- Oral tablets (sulfamethoxazole/trimethoprim 400 mg/80 mg, 800 mg/160 mg)
- Oral suspension (sulfamethoxazole/trimethoprim 200 mg + 40 mg per 5 mL)
- Intravenous injection (sulfamethoxazole/trimethoprim 80 mg/16 mg per mL)
Adult Dosing
- Urinary tract infections / Shigellosis: 1 double-strength (800/160 mg) tablet PO every 12 hours for 10-14 days
- Pneumocystis jirovecii pneumonia (PJP) treatment: 15-20 mg/kg/day (based on trimethoprim component) IV divided every 6 to 8 hours for 14-21 days
- PJP prophylaxis: 1 double-strength tablet PO daily or 1 single-strength tablet PO daily
Pediatric Dosing
- Infants and children >2 months - Acute otitis media / UTI: 40 mg/kg/day (sulfamethoxazole) and 8 mg/kg/day (trimethoprim) PO divided every 12 hours for 10 days
- PJP treatment (children >2 months): 15-20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours
- PJP prophylaxis (children >2 months): 150 mg/m²/dose (trimethoprim component) PO twice daily, 3 consecutive days per week
Indications
- Treatment of urinary tract infections caused by susceptible strains of E. coli, Klebsiella, and Enterobacter
- Treatment and prophylaxis of Pneumocystis jirovecii pneumonia in immunocompromised patients
- Treatment of acute otitis media in children due to Haemophilus influenzae or Streptococcus pneumoniae
- Treatment of acute exacerbations of chronic bronchitis and traveler's diarrhea
Mechanism of Action
- Sulfonamides competitively inhibit dihydropteroate synthase, blocking bacterial synthesis of folic acid
- Trimethoprim inhibits dihydrofolate reductase, blocking the reduction of dihydrofolate to tetrahydrofolate
- Synergistic sequential blockade of bacterial folic acid pathway inhibits purine and nucleic acid synthesis
Contraindications
- Known hypersensitivity to sulfonamides or trimethoprim
- Infants under 2 months of age due to risk of kernicterus
- Pregnancy at term and nursing mothers due to risk of hyperbilirubinemia in the neonate
- Documented megaloblastic anemia due to folate deficiency
- Severe renal or hepatic insufficiency when monitoring is not feasible
Adverse Reactions
- Hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and rash
- Hematologic toxicities including agranulocytosis, aplastic anemia, leukopenia, and thrombocytopenia
- Gastrointestinal disturbances including nausea, vomiting, anorexia, and diarrhea
- Metabolic abnormalities such as hyperkalemia and hyponatremia
- Renal impairment, crystalluria, and interstitial nephritis
Drug Interactions
- Potentiation of warfarin anticoagulant effect, increasing risk of bleeding
- Increased serum levels and toxicity risk of methotrexate due to displacement from plasma proteins
- Increased risk of hyperkalemia and renal dysfunction when used concurrently with ACE inhibitors or ARBs
- Elevated plasma concentrations of digoxin and phenytoin through inhibition of hepatic metabolism
- Reduced efficacy of oral contraceptives due to altered gut flora and enterohepatic circulation
Curated Content: Needs Vetting Before Put to Clinical Use