What is the recommended dosing of isoniazid (Isoniazid) for Tuberculosis Preventive Therapy (TPT)?

Isoniazid Dosing for Tuberculosis Preventive Therapy (TPT)

For adults, administer isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months, or 15 mg/kg (maximum 900 mg) twice weekly under directly observed therapy (DOT), with at least 270 doses required for completion. 1

Standard Adult Dosing Regimens

Daily Therapy

• 5 mg/kg daily (maximum 300 mg) is the recommended dose for adults 1
• Requires at least 270 doses over 9 months (up to 12 months if interruptions occur) 1
• Completion is based on total doses administered, not duration alone 1

Intermittent Therapy

• 15 mg/kg twice weekly (maximum 900 mg) requires at least 76 doses over 9 months 1
• DOT is mandatory for all intermittent dosing regimens 1
• Some experts also recommend DOT for daily regimens when operationally feasible 1

Pediatric Dosing

Children and Adolescents

• 10-15 mg/kg daily (maximum 300 mg) for daily therapy 1
• 20-30 mg/kg twice weekly (maximum 900 mg) for intermittent therapy 1
• The International Union Against Tuberculosis and Lung Diseases (IUATLD) and WHO recommend 5 mg/kg up to 300 mg/day, though others recommend 10 mg/kg 1
• Pharmacokinetic studies demonstrate that 5 mg/kg achieves satisfactory serum concentrations and clinical outcomes 1, 2

Special Population Considerations

HIV-Infected Patients

• Use the same dosing as HIV-negative patients but extend duration to 12 months minimum 1
• Daily isoniazid regimens should consist of at least 270 doses over 9-12 months 1
• For patients on protease inhibitors or NNRTIs, isoniazid monotherapy is preferred (rifampin-containing regimens are contraindicated) 1

Pregnant Women

• Begin isoniazid preventive therapy immediately when recent infection or high-risk conditions are documented 1
• Use standard adult dosing: 5 mg/kg daily (maximum 300 mg) 1

Pyridoxine Supplementation

Administer pyridoxine (vitamin B6) 25-50 mg daily to all at-risk patients 1:

• Pregnant women and breastfeeding infants 1
• Persons with HIV infection 1
• Patients with diabetes, alcoholism, malnutrition, or chronic renal failure 1
• Patients of advanced age 1
• For patients with peripheral neuropathy, increase pyridoxine to 100 mg daily 1

Monitoring Requirements

Monthly Clinical Evaluation

• All patients require monthly assessment of adherence and medication side effects 1
• This is mandatory throughout the entire treatment course 1

Hepatotoxicity Surveillance

• Asymptomatic aminotransferase elevations up to 5 times the upper limit of normal occur in 10-20% of patients and usually normalize with continued therapy 1
• Clinical hepatitis occurs in approximately 0.6% of patients receiving isoniazid alone 1
• The risk increases with age: uncommon in those <20 years but approaches 2% in those aged 50-64 years 1
• Stop isoniazid immediately if symptoms of hepatitis develop (fever, malaise, vomiting, jaundice, weight loss) 1

Treatment Interruptions and Reinitiation

• When therapy is interrupted for ≥2 months, perform a medical examination to rule out active TB disease before restarting 1
• Either continue the original regimen to complete the recommended total doses, or restart the entire regimen 1
• Extend the calendar duration up to 12 months if interruptions occur, ensuring the minimum dose count is achieved 1

Alternative Shorter Regimens

The 3-month once-weekly isoniazid (900 mg) plus rifapentine (900 mg) regimen is now preferred over 9 months of isoniazid alone due to:

• Equivalent effectiveness (0.19% vs 0.43% tuberculosis development) 3
• Higher completion rates (82.1% vs 69.0%) 3
• Lower hepatotoxicity (0.4% vs 2.7%) 3

However, this combination regimen is not addressed in the original question about isoniazid dosing specifically for TPT.

Critical Pitfalls to Avoid

• Never count calendar time alone—completion requires the minimum number of doses (270 for daily, 76 for twice-weekly) 1
• Do not use intermittent dosing without DOT—this is associated with treatment failure and resistance 1
• Do not continue isoniazid if symptomatic hepatitis develops—fatal hepatitis has been associated with continued administration despite symptoms 1
• Do not omit pyridoxine in at-risk populations—peripheral neuropathy is preventable with supplementation 1