What is the recommended dose of trimethoprim (TMP)-sulfamethoxazole (SMX) for adults?

Trimethoprim-Sulfamethoxazole Dosing for Adults

For most adult indications, the standard dose of trimethoprim-sulfamethoxazole (TMP-SMX) is one double-strength tablet (160 mg TMP/800 mg SMX) twice daily, with duration varying by indication from 3 to 14 days. 1, 2

Standard Dosing by Indication

Urinary Tract Infections

• One double-strength tablet (160/800 mg) every 12 hours for 10-14 days 1, 2
• For uncomplicated cystitis in women: 160/800 mg twice daily for 3 days is an acceptable alternative when local E. coli resistance is <20% 3
• Single-dose therapy (320 mg TMP/1,600 mg SMX as a one-time dose) has demonstrated 93% efficacy for acute uncomplicated UTI in women, though this is not the FDA-approved regimen 4

Acute Exacerbations of Chronic Bronchitis

• One double-strength tablet every 12 hours for 14 days 1, 2

Traveler's Diarrhea

• One double-strength tablet every 12 hours for 5 days 1, 2
• When combined with loperamide, optimal efficacy is achieved with a loading dose of 320/1,600 mg followed by 160/800 mg twice daily for 3 days 5

Shigellosis

• One double-strength tablet every 12 hours for 5 days 1, 2

Pneumocystis Pneumonia (PCP)

Treatment Dosing

• 75-100 mg/kg/day of sulfamethoxazole and 15-20 mg/kg/day of trimethoprim, divided into 4 doses every 6 hours for 14-21 days 1, 2
• For a 70 kg adult at the upper limit: 2 double-strength tablets (or 4 single-strength tablets) every 6 hours 1, 2
• Important caveat: This high-dose regimen produces excessive serum concentrations (mean peak TMP 13.6 mcg/mL) and causes significant toxicity, with 42% of healthy subjects unable to complete even 3 days of therapy due to gastrointestinal and CNS adverse effects 6

Prophylaxis Dosing

• One double-strength tablet daily is the preferred regimen for PCP prophylaxis in HIV-infected adults with CD4+ counts <200 cells/µL 3
• Alternative schedules with equivalent efficacy: one double-strength tablet three times weekly on consecutive days 3

Intravenous Dosing

• Trimethoprim 320 mg and sulfamethoxazole 1,600 mg per day, divided into 2 doses every 12 hours 7
• For severe infections or PCP: 150 mg TMP/750 mg SMX per m² body surface area every 8-12 hours, with dosing interval adjusted based on age and renal function 8

Renal Impairment Adjustments

Dosing must be reduced when creatinine clearance falls below 30 mL/min: 1, 2

• CrCl >30 mL/min: Standard dosing
• CrCl 15-30 mL/min: Reduce dose by 50% (half the usual regimen)
• CrCl <15 mL/min: Use not recommended

For IV dosing in renal failure, the dosing interval in hours should equal 12 times the serum creatinine level in mg/dL (maximum 48-hour interval) 8

Critical Safety Considerations

• Monitor complete blood counts monthly during prophylaxis, as neutropenia correlates directly with serum TMP and SMX concentrations 9, 6
• Contraindicated in pregnancy (especially first and third trimesters), nursing mothers, and infants <2 months due to kernicterus risk 7, 1, 2
• Ensure adequate hydration to prevent crystalluria and renal stones 7
• Common adverse effects include rash (most frequent), gastrointestinal disturbances, and hematologic abnormalities including thrombocytopenia 9, 7
• Permanently discontinue if life-threatening toxicity occurs 9

Key Clinical Pitfalls

The most common dosing error is using treatment doses for prophylaxis—prophylaxis requires only one double-strength tablet daily or three times weekly, not twice daily 3. Conversely, using prophylactic doses for active PCP treatment will result in therapeutic failure, as treatment requires 4-6 times higher daily doses 1, 2. Additionally, the FDA-approved PCP treatment dose frequently causes intolerable toxicity; serum drug monitoring should be considered to maintain peak TMP levels of 5-10 mcg/mL rather than the 13+ mcg/mL achieved with standard dosing 6, 8.