What is the recommended dose of Sulfatrim (trimethoprim/sulfamethoxazole) for pediatric patients?

Sulfatrim (Trimethoprim/Sulfamethoxazole) Pediatric Dosing

For most pediatric infections in children over 2 months of age, administer 8-12 mg/kg/day of trimethoprim (40-60 mg/kg/day of sulfamethoxazole) divided into 2 doses given every 12 hours. 1, 2, 3

Age-Based Contraindication

• Do not use Sulfatrim in infants under 2 months of age due to the risk of kernicterus from displacement of bilirubin from albumin binding sites 1, 3

Standard Dosing by Indication

Urinary Tract Infections and Acute Otitis Media

• 8 mg/kg/day trimethoprim (40 mg/kg/day sulfamethoxazole) divided every 12 hours for 10 days for UTIs 3
• Same dosing for acute otitis media in children over 2 months 3
• Alternative dosing from WHO guidelines: 4 mg/kg trimethoprim (20 mg/kg sulfamethoxazole) twice daily for 5 days for UTIs 4

Skin and Soft Tissue Infections

• 8-12 mg/kg/day trimethoprim divided every 12 hours for 7-10 days 1

Pneumocystis jirovecii Pneumonia (PCP)

• Treatment: 15-20 mg/kg/day trimethoprim (75-100 mg/kg/day sulfamethoxazole) divided into 3-4 doses every 6-8 hours for 21 days 4, 3
• This higher dosing is critical for severe PCP and should be given intravenously initially, then switched to oral once acute pneumonitis resolves 4
• Prophylaxis: 150 mg/m²/day trimethoprim (750 mg/m²/day sulfamethoxazole) divided twice daily on 3 consecutive days per week, not to exceed 320 mg trimethoprim and 1600 mg sulfamethoxazole total daily 3

Shigellosis

• 8 mg/kg/day trimethoprim (40 mg/kg/day sulfamethoxazole) divided every 12 hours for 5 days 3

Pharmacokinetic Rationale

The standard 8/40 mg/kg/day dosing divided every 12 hours achieves therapeutic targets matching adult exposure and maintains free trimethoprim concentrations above the MIC for over 50% of the dosing interval for bacteria with MIC ≤0.5 mg/L in >90% of children 2, 5. For more resistant organisms with MIC up to 1 mg/L, higher doses of 12-15 mg/kg/day trimethoprim may be required in younger children 5.

Formulation Considerations

• Use liquid suspension for children weighing <16 kg to ensure accurate dosing 2
• Liquid formulation contains 40 mg sulfamethoxazole and 8 mg trimethoprim per mL 3
• Tablets are available as 400/80 mg (single strength) and 800/160 mg (double strength) 3

Renal Dose Adjustment

Adjust dosing based on creatinine clearance: 3

• CrCl >30 mL/min: Standard dosing
• CrCl 15-30 mL/min: Reduce dose by 50%
• CrCl <15 mL/min: Use not recommended

Trimethoprim clearance is inversely related to serum creatinine, requiring dose reduction in renal impairment 5.

Monitoring Requirements

• Obtain complete blood count with differential and platelet count at treatment initiation 2
• Repeat CBC monthly during prolonged therapy to assess for hematologic toxicity including neutropenia, thrombocytopenia, and anemia 4, 2
• Monitor renal function, particularly in patients with baseline renal impairment 1

Critical Safety Warnings

Use with extreme caution or avoid in: 1, 2

• G6PD deficiency: Risk of severe hemolytic anemia
• Hepatic insufficiency: Sulfamethoxazole clearance is inversely related to albumin concentration 5
• Known sulfonamide or trimethoprim hypersensitivity

Common Adverse Effects

Adverse reactions occur in approximately 15% of HIV-infected children, lower than in adults 4:

• Dermatologic: Rash (including erythema multiforme; rarely Stevens-Johnson syndrome) 4, 1
• Hematologic: Neutropenia, thrombocytopenia, megaloblastic anemia 4, 1
• Gastrointestinal: Usually mild complaints 4
• Hepatic: Hepatitis 4
• Renal: Interstitial nephritis 4

For mild rash, temporarily discontinue and restart when resolved; for urticarial rash or Stevens-Johnson syndrome, permanently discontinue 4.

Significant Drug Interactions

Exercise caution with: 1, 2

• Methotrexate: Increased methotrexate toxicity
• Warfarin and other anticoagulants: Enhanced anticoagulant effect
• Oral hypoglycemics: Increased hypoglycemia risk
• Thiazide diuretics: Increased risk of thrombocytopenia
• Anticonvulsants (phenytoin): Altered metabolism

Clinical Pearls

• The combination achieves high urinary concentrations invariably >10 times the MIC for common uropathogens 6
• Steady-state serum levels are reached after 4 or more days of treatment 6
• Peak serum concentrations occur 2-4 hours after oral dosing 6
• Trimethoprim clearance is 5 times greater than sulfamethoxazole clearance, but both have similar half-lives of approximately 10 hours in children 6, 7