What is the recommended daily Isoniazid (Isoniazid) regimen for a patient requiring Tuberculosis (TB) preventive therapy, considering factors such as age, weight, and potential risk factors like Human Immunodeficiency Virus (HIV) infection?

TB Preventive Therapy: Isoniazid Daily Regimen

Standard Daily Dosing

For TB preventive therapy, administer isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months in adults, or 10-15 mg/kg (maximum 300 mg) daily for 9 months in children, with treatment completion defined as at least 270 doses administered within 9-12 months. 1, 2

Adult Dosing

• Daily regimen: 5 mg/kg (maximum 300 mg) once daily for 9 months 1
• Minimum required doses: At least 270 doses over 9 months (up to 12 months if interruptions occur) 1, 2
• Completion criteria: Based on total doses administered, not duration alone 1, 3

Pediatric Dosing

• Recommended dose: 10-15 mg/kg daily (maximum 300 mg) 2, 1
• Duration: 9 months for HIV-negative children; 12 months for HIV-infected children 2, 3
• Important consideration: Younger children require higher per-kilogram dosing (8-12 mg/kg) to achieve adequate plasma concentrations comparable to adults, as children prescribed 4-6 mg/kg achieve peak concentrations 58% lower than those on 8-10 mg/kg 4

HIV-Infected Patients

HIV-infected patients require extended treatment duration of 12 months minimum, using the same weight-based dosing as HIV-negative patients. 2, 3

• Daily regimen: 10-15 mg/kg (maximum 300 mg) daily for 12 months 2
• Minimum doses: At least 270 doses over 12 months 2
• Alternative consideration: Recent evidence demonstrates that 1 month of daily rifapentine plus isoniazid is noninferior to 9 months of isoniazid alone, with 97% completion versus 90% for the 9-month regimen 5

Pyridoxine Supplementation

All patients at risk for peripheral neuropathy must receive pyridoxine 25-50 mg daily concurrently with isoniazid. 1

High-Risk Groups Requiring Pyridoxine:

• Pregnant women 1
• Breastfeeding infants 1
• Persons with HIV infection 1, 2
• Patients with diabetes, alcoholism, malnutrition, or renal failure 1

Mandatory Monitoring Requirements

Monthly clinical evaluation is required throughout the entire treatment course to assess adherence and monitor for hepatotoxicity symptoms. 1, 2, 3

Baseline Assessment:

• Exclude active TB disease through history, physical examination, chest radiography, and sputum cultures if any clinical suspicion exists 6
• Obtain baseline liver function tests for patients with underlying liver disease, HIV infection, or concurrent hepatotoxic medications 6

Monthly Monitoring:

• Assess adherence to treatment 1, 2
• Screen for hepatitis symptoms (nausea, vomiting, abdominal pain, jaundice, dark urine) 1
• Instruct patients to discontinue isoniazid immediately and contact provider if hepatitis symptoms develop 6

Hepatotoxicity Risk:

• Asymptomatic aminotransferase elevations occur in 10-20% of patients 1
• Clinical hepatitis occurs in approximately 0.6% of patients receiving isoniazid alone 1
• Hepatotoxicity rates: 0.36% with 6-month treatment, 0.52% with 12-month treatment 7

Treatment Interruptions

If treatment is interrupted for ≥2 months, perform a medical examination to rule out active TB disease before restarting therapy. 1, 2

• Options after interruption: Either continue the original regimen to complete the recommended total doses, or restart the entire regimen 2
• Calculation of completion: When interruptions occur, extend the calendar duration to ensure the minimum number of doses (270) is administered 1

Alternative Twice-Weekly Regimen

For patients requiring directly observed therapy, isoniazid can be administered at 15 mg/kg (maximum 900 mg) twice weekly for 9 months, requiring at least 76 doses for completion. 1, 2

• Adult dose: 15 mg/kg (maximum 900 mg) twice weekly 1
• Pediatric dose: 20-30 mg/kg (maximum 900 mg) twice weekly 2
• Mandatory requirement: Directly observed therapy must be used with all intermittent dosing regimens 2

Critical Pitfalls to Avoid

• Do not use 6-month isoniazid in immunocompromised patients: The 9-month regimen provides superior protection in vulnerable populations 6
• Do not prescribe rifampin-based regimens without reviewing drug interactions: Rifamycins interact with protease inhibitors, NNRTIs, and numerous other medications 2, 6
• Do not base completion on duration alone: Treatment completion requires the minimum number of doses (270 for daily, 76 for twice-weekly), regardless of calendar time 1, 3
• Do not omit pyridoxine in high-risk patients: Failure to supplement increases risk of peripheral neuropathy 1, 2