From the Guidelines
The maximum recommended dose of pyrazinamide is 15 mg/kg per day, not to exceed 1 g/day, for adults. This dosing recommendation is based on the guidelines for the treatment of tuberculosis, as outlined in the study published in the MMWR Recommendations and Reports 1 and further supported by the American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America guidelines 1.
Key Considerations
- For persons over 59 years of age, the dose should be reduced to 10 mg/kg per day (750 mg) 1.
- The dosing frequency should be reduced (i.e., 12–15 mg/kg per dose two or three times per week) in persons with renal insufficiency 1.
- Children's dosing is slightly different, with a maximum of 20–40 mg/kg per day (1 g/day) 1.
Clinical Application
Pyrazinamide is a critical component of the intensive phase of tuberculosis treatment, typically used for the first 2 months as part of a multi-drug regimen that includes isoniazid, rifampin, and ethambutol. Monitoring for hepatotoxicity is essential during treatment, as this is a significant potential adverse effect. Liver function tests should be checked before starting therapy and periodically during treatment, especially in patients with pre-existing liver disease.
From the FDA Drug Label
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 dose of pyrazinamide is 2 g per day when given as a daily regimen, although the drug label also states that 3 g per day should not be exceeded 2.
From the Research
Maximum Dose of Pyrazinamide
The maximum dose of pyrazinamide is not explicitly stated in the provided studies. However, the following information can be gathered:
- The standard antitubercular regimen includes a combination of isoniazid, rifampicin, and pyrazinamide 3.
- Pyrazinamide is a major hepatotoxin, and its hepatotoxicity may be related to the dose used 4.
- A study found that preventive treatment with rifampin-pyrazinamide caused severe hepatotoxicity more often than preventive treatment with isoniazid, especially in patients <25 years old, and when the pyrazinamide dose was > or =30 mg/kg 4.
- Another study found that adding pyrazinamide to isoniazid and rifampin increases the risk of hepatotoxicity appreciably 5.
- A review of literature found that children and adults receiving the same mg/kg body weight pyrazinamide dosage will reach a similar maximum concentration (C(max)) 6.
- A study found that high doses of isoniazid per kg of body weight were independently associated with the development of hepatotoxicity due to the RHZ scheme (rifampicin, isoniazid, and pyrazinamide) 7.
Key Points
- Pyrazinamide is a major hepatotoxin, and its dose may be related to the risk of hepatotoxicity.
- The maximum dose of pyrazinamide is not explicitly stated in the provided studies.
- High doses of pyrazinamide (> or =30 mg/kg) may increase the risk of hepatotoxicity.
- Children and adults receiving the same mg/kg body weight pyrazinamide dosage will reach a similar C(max).
- High doses of isoniazid per kg of body weight were independently associated with the development of hepatotoxicity due to the RHZ scheme.
Dosage Considerations
- The dosage of pyrazinamide should be carefully considered to minimize the risk of hepatotoxicity.
- Patients with underlying liver test abnormalities should not be given pyrazinamide 3.
- Isoniazid and pyrazinamide should be administered at the lowest dosage within their respective therapeutic ranges 3.
- Serum transaminase levels should be monitored regularly during treatment with pyrazinamide 3.