From the Guidelines
The maximum dosage of pyrazinamide in anti-tubercular treatment is 2000 mg per day for adults, with a standard recommended dose of 20-40 mg/kg body weight orally once daily, not exceeding 2 g/day, as stated in the guidelines from 1.
Key Considerations
- The dosage of pyrazinamide may vary depending on the patient's weight and the specific treatment regimen, with a typical range of 1000-2000 mg daily for adults.
- For intermittent regimens, such as three times weekly, the maximum dose may increase, but should not exceed 3000 mg per dose, as noted in 1.
- Pyrazinamide is typically administered as part of a multi-drug regimen, including isoniazid, rifampin, and ethambutol, during the intensive phase of TB treatment, which usually lasts for 2 months.
- Patients should be monitored for potential side effects, including hepatotoxicity, hyperuricemia, and arthralgia, during treatment with pyrazinamide, as recommended in 1.
Dosage Adjustments
- Dose adjustments may be necessary for patients with renal impairment, with a recommended reduction to 25-30 mg/kg three times per week for those with creatinine clearance <30 mL/min, as suggested in 1.
- The medication should be taken once daily with food to minimize gastrointestinal upset.
Mechanism of Action
- Pyrazinamide works by converting to pyrazinoic acid, which disrupts membrane energetics and inhibits the fatty acid synthase I enzyme in Mycobacterium tuberculosis, making it particularly effective in acidic environments like those found in inflammatory lesions, as described in 1.
From the FDA Drug Label
Pyrazinamide is administered orally, 15 to 30 mg/kg once daily Three grams per day should not be exceeded. The CDC recommendations do not exceed 2 g per day when given as a daily regimen Drug Maximal Daily Dose in Children and Adults Pyrazinamide 2 g
The maximum dosage of pyrazinamide is 2 g per day when given as a daily regimen, as recommended by the CDC, although the drug label also states that 3 g per day should not be exceeded 2.
From the Research
Anti-Tubercular Treatment Maximum Dosage of Pyrazinamid
- The maximum dosage of pyrazinamid is not explicitly stated in the provided studies, but the optimal dosing strategies are discussed in several studies 3, 4, 5, 6.
- A study published in 2024 suggests that flat dosing of pyrazinamide at 1,000 mg/d would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis 3.
- Another study published in 2021 found that pyrazinamide's microbiological efficacy increases with increasing drug concentrations, but optimizing pyrazinamide alone is unlikely to be sufficient to allow tuberculosis treatment shortening; rather, rifampicin dose would need to be increased in parallel 4.
- A study published in 2012 reviewed the efficacy and pharmacokinetics of pyrazinamide in children and adults, and found that children and adults receiving the same mg/kg body weight PZA dosage will reach a similar maximum concentration (C(max)) 5.
- A prospective population pharmacokinetic study published in 2022 investigated first-line antituberculosis drug exposures in pediatric patients and suggested a new fixed-dose combination (FDC) formulation and revised weight bands to optimize dosing 6.
- The optimal dosage of pyrazinamide may vary depending on the specific patient population and treatment regimen, and further research is needed to determine the maximum safe and effective dosage 3, 4, 5, 6.