What is the maximum recommended dosage of isoniazid (Isoniazid) for adults?

From the Guidelines

The maximum recommended dosage of isoniazid for adults is 15 mg/kg per day, which translates to a maximum of 1.0 g/day, as stated in the most recent and highest quality study 1. This dosage is typically used for both active tuberculosis treatment and latent tuberculosis infection.

• For most adults, the daily dose is 300 mg, but this can be adjusted based on weight.
• For intermittent dosing regimens, the maximum dose may be increased to 900 mg when administered two or three times weekly, but only under direct observation by healthcare providers.
• Isoniazid is a bactericidal antibiotic that works by inhibiting mycolic acid synthesis, which is essential for the mycobacterial cell wall.
• Patients taking isoniazid should supplement with pyridoxine (vitamin B6), typically 25-50 mg daily, to prevent peripheral neuropathy, a common side effect.
• Liver function tests should be monitored regularly during treatment, as isoniazid can cause hepatotoxicity.
• Alcohol should be avoided while taking this medication.
• The drug is typically administered on an empty stomach for optimal absorption, but can be taken with food if gastrointestinal upset occurs. It's worth noting that for persons greater than 59 years of age, the dose should be reduced to 10 mg/kg per day (750 mg) 1. Additionally, the dosing frequency should be reduced in persons with renal insufficiency 1. The most recent and highest quality study 1 provides a comprehensive guide to the dosing of isoniazid and other antituberculosis drugs, and should be consulted for specific guidance on dosing in different patient populations.

From the FDA Drug Label

Adults over 30 kg: 300 mg per day in a single dose. In situations where adherence with daily preventative therapy cannot be assured, 20 mg/kg to 30 mg/kg (not to exceed 900 mg) twice weekly under the direct observation of a health care worker at the time of administration

The maximum recommended dosage of isoniazid for adults is 900 mg twice weekly, under direct observation, for preventative therapy when daily adherence cannot be assured. For daily treatment, the maximum dose is 300 mg per day in a single dose for adults over 30 kg 2.

From the Research

Maximum Dosage of Isoniazid for Adults

The maximum recommended dosage of isoniazid for adults is not explicitly stated in the provided studies. However, the following information can be gathered:

• A study published in 2019 3 suggests that a dose of 900 mg per day may be required to cover strains with MIC up to 0.125 mg/L, which accounts for 80% of clinical isolates.
• A study published in 1999 4 found that high-dose isoniazid (100 mg/kg of body weight) was not more effective than standard-dose isoniazid (25 mg/kg) for therapy of tuberculosis infections caused by INH-resistant mutants of M. tuberculosis Erdman.
• A study published in 2020 5 explored the optimal dose of isoniazid for patients with isoniazid-resistant TB mediated by inhA mutations and found that isoniazid 10-15 mg/kg daily had activity against TB strains with inhA mutations similar to that of 5 mg/kg against drug-sensitive strains.
• A study published in 2009 6 focused on pediatric dosing guidelines and found that younger children require higher doses of isoniazid per kilogram of body weight to achieve isoniazid concentrations similar to those in adults, recommending a daily isoniazid dose of 8-12 mg/kg.
• A study published in 1986 7 reported a higher risk of hepatitis with isoniazid 20 mg/kg (39%) compared to 12 mg/kg (16%) in children with tuberculous meningitis.

Key Findings

• The maximum dosage of isoniazid for adults is not explicitly stated in the provided studies.
• Higher doses of isoniazid may be required to cover strains with higher MIC values.
• The optimal dose of isoniazid for patients with isoniazid-resistant TB mediated by inhA mutations is 10-15 mg/kg daily.
• Pediatric dosing guidelines recommend a daily isoniazid dose of 8-12 mg/kg for younger children.
• Higher doses of isoniazid may increase the risk of hepatitis, particularly in slow acetylators.

Dosage Considerations

• The dosage of isoniazid should be individualized based on the patient's weight, age, and acetylator status.
• Higher doses of isoniazid may be necessary to achieve optimal efficacy against TB strains with higher MIC values.
• The risk of hepatitis should be carefully monitored, particularly in patients receiving higher doses of isoniazid.