What is the recommended dose of pyrazinamide for a patient?

Pyrazinamide Dosing for Tuberculosis

For drug-susceptible tuberculosis, pyrazinamide should be dosed at 15-30 mg/kg daily (maximum 2 g/day) for the initial 2 months of treatment, with weight-banded dosing of 1,000 mg for 40-55 kg, 1,500 mg for 56-75 kg, and 2,000 mg for 76-90 kg patients. 1

Standard Daily Dosing Regimen

Weight-Based Dosing for Adults:

• 40-55 kg: 1,000 mg daily (18.2-25.0 mg/kg) 1
• 56-75 kg: 1,500 mg daily (20.0-26.8 mg/kg) 1
• 76-90 kg: 2,000 mg daily (22.2-26.3 mg/kg) 1

The FDA label confirms pyrazinamide is administered at 15-30 mg/kg once daily, with a maximum of 2 g per day when given as a daily regimen, and should not exceed 3 g per day under any circumstances. 2

Intermittent Dosing Options

Twice-Weekly Dosing (for directly observed therapy):

• 40-55 kg: 2,000 mg (36.4-50.0 mg/kg) 1
• 56-75 kg: 3,000 mg (40.0-53.6 mg/kg) 1
• 76-90 kg: 4,000 mg (44.4-52.6 mg/kg) 1

Thrice-Weekly Dosing:

• 40-55 kg: 1,500 mg (27.3-37.5 mg/kg) 1
• 56-75 kg: 2,500 mg (33.3-44.6 mg/kg) 1
• 76-90 kg: 3,000 mg (33.3-39.5 mg/kg) 1

The twice-weekly regimen uses 50-75 mg/kg based on lean body weight and has been developed specifically to promote patient compliance in outpatient settings. 2

Pediatric Dosing

• Daily dosing: 15-30 mg/kg once daily (maximum 2 g) 1, 2
• Twice-weekly dosing: 50-70 mg/kg (maximum 4 g) 1

Children should be managed essentially the same as adults using appropriately adjusted doses, with dosages rounded up to facilitate prescription of easily given volumes of syrup or appropriate tablet strengths. 1, 3

Duration of Therapy

Pyrazinamide is administered for the initial 2 months only of a 6-month treatment regimen for drug-susceptible tuberculosis. 1, 2 It should always be administered with other effective antituberculosis drugs (isoniazid, rifampin, and ethambutol). 2

For patients with cavitation on initial chest radiograph and positive cultures at 2 months, the continuation phase should be extended to 7 months (total 9 months), but pyrazinamide is still only given for the first 2 months. 1

Special Populations and Considerations

HIV-Coinfected Patients:

• Use the same dosing as HIV-negative patients 1
• May require longer courses of therapy overall, though pyrazinamide duration remains 2 months 2
• Rifabutin-based regimens may be necessary when using protease inhibitors or NNRTIs 1

When Pyrazinamide Cannot Be Used: If pyrazinamide must be excluded due to adverse reactions, treatment should consist of rifampin and isoniazid for 9 months (not 6 months), supplemented with ethambutol for the initial 2 months. 4, 5 This represents a 3-month extension because pyrazinamide's sterilizing activity allows treatment shortening in drug-susceptible TB. 5

Emerging Evidence on Flat Dosing

Recent high-quality research suggests that flat dosing of 1,000 mg daily (regardless of weight) may optimize treatment outcomes better than weight-banded dosing. 6 This 2024 phase 3 randomized controlled trial found that flat dosing at 1,000 mg would permit an additional 13.1% of patients to achieve therapeutic drug levels within the optimal therapeutic window (231-355 mg·h/L), compared to current weight-banded dosing. 6

However, current guidelines have not yet incorporated this finding, so weight-banded dosing remains the standard of care. 1

Critical Monitoring Requirements

• Monitor all patients monthly for adherence and adverse effects 1
• Check for symptoms of hepatotoxicity (fever, malaise, vomiting, jaundice, unexplained deterioration) 4
• Do not discontinue pyrazinamide for asymptomatic hyperuricemia alone, as this is expected and clinically insignificant 5
• Baseline and regular liver function monitoring is required in patients with chronic liver disease 1

Common Pitfalls to Avoid

• Do not use pyrazinamide beyond 2 months in standard drug-susceptible TB regimens 1, 2
• Do not exceed 2 g daily for daily dosing regimens 1, 2
• Do not use combined drug preparations when reintroducing medications after adverse reactions, as this prevents identification of the offending agent 4, 5
• Do not base dosing solely on total body weight in obese patients; dosing should be based on lean body weight 1