Pyrazinamide Dosing for Disseminated TB in a 74 kg Patient
For a 74 kg patient with disseminated tuberculosis, administer pyrazinamide 2,000 mg once daily for the initial 2 months of treatment as part of a multi-drug regimen. 1, 2
Weight-Based Dosing Calculation
A patient weighing 74 kg falls into the 56-75 kg weight band, which corresponds to a daily dose of 1,500 mg (20.0-26.8 mg/kg). 1, 2
However, patients at the upper end of this weight band (approaching 76 kg) should receive 2,000 mg daily to ensure adequate drug exposure. 1
The 76-90 kg weight band receives 2,000 mg daily (22.2-26.3 mg/kg), and since 74 kg is only 2 kg below this threshold, the higher dose is appropriate. 1, 2
Rationale for Dose Selection
The CDC/ATS/IDSA guidelines specify that pyrazinamide dosing should be based on lean body weight, with 2,000 mg being the maximum daily dose regardless of weight. 1, 3
For disseminated TB, the same dosing principles apply as for pulmonary TB, with pyrazinamide administered for the initial 2-month intensive phase. 1, 3
Recent pharmacokinetic studies demonstrate that more than 50% of patients weighing less than 55 kg achieve subtherapeutic exposures with current weight-banded dosing, suggesting that patients at higher weight bands may benefit from the upper dosing limits. 4
Treatment Duration and Regimen Structure
Pyrazinamide should be administered for the initial 2 months only as part of a 6-month treatment regimen for drug-susceptible TB. 1, 2, 3
For disseminated TB, if there is evidence of CNS involvement (tuberculous meningitis), treatment duration should be extended to 12 months total, though pyrazinamide is still only given for the first 2 months. 5
A lumbar puncture should be performed in disseminated/miliary TB to rule out meningeal involvement, which determines whether 6-month or 12-month therapy is required. 5
Multi-Drug Combination Requirements
Pyrazinamide must always be administered with other effective antituberculosis drugs—never as monotherapy—typically in combination with isoniazid, rifampin, and ethambutol. 1, 3
The standard four-drug regimen for the initial phase includes isoniazid (5 mg/kg, max 300 mg), rifampin (10 mg/kg, max 600 mg), pyrazinamide (15-30 mg/kg, max 2 g), and ethambutol (15-25 mg/kg, max 2.5 g). 3
Alternative Dosing Schedules
If twice-weekly directly observed therapy (DOT) is used instead of daily dosing, the dose would be 3,000 mg (40.0-53.6 mg/kg) for the 56-75 kg weight band. 1, 2
For thrice-weekly DOT, the dose would be 2,500 mg (33.3-44.6 mg/kg) for the 56-75 kg weight band. 1, 2
Daily dosing is preferred over intermittent dosing for HIV-infected patients with CD4 counts <100 cells/μL due to higher rates of treatment failure with twice-weekly regimens. 1
Monitoring Requirements
Patients should be assessed monthly for adherence to the treatment regimen and adverse effects, including hepatotoxicity and gastrointestinal symptoms. 1, 2
Baseline liver function tests should be obtained, with regular monitoring (weekly for 2 weeks, then biweekly for 2 months) required for patients with known chronic liver disease. 1
For patients with normal pre-treatment liver function, routine monitoring is not required unless fever, malaise, vomiting, jaundice, or unexplained deterioration occur. 1
If AST/ALT rises to 5 times normal or bilirubin rises, pyrazinamide (along with rifampin and isoniazid) should be stopped immediately. 1
Special Considerations for Disseminated TB
Patients with disseminated TB who have cavitation on initial chest radiograph and positive cultures at 2 months are at increased risk of relapse and should have their continuation phase extended to 7 months (total 9 months), though pyrazinamide is still only given for the first 2 months. 1, 2
HIV-coinfected patients with disseminated TB may require longer courses of therapy and should receive daily (not twice-weekly) dosing during both the initial and continuation phases. 1, 3
Common Pitfalls to Avoid
Do not use weight-banded dosing tables rigidly—patients at the upper end of a weight band (like 74 kg in the 56-75 kg band) should receive the higher dose to ensure adequate exposure. 1
Do not continue pyrazinamide beyond 2 months in drug-susceptible TB, even if extending total treatment duration to 9 months for high-risk patients. 1, 2
Do not use fixed-dose combination tablets (Rifater) for patients weighing >90 kg without adding additional pyrazinamide tablets, as the combination provides inadequate pyrazinamide dosing at higher weights. 1
Do not assume disseminated TB can be treated with a 6-month regimen without first ruling out CNS involvement via lumbar puncture. 5