What is the recommended treatment regimen for Isoniazid (INH) preventive therapy?

Isoniazid Preventive Therapy: Recommended Treatment Regimens

For adults and children with latent tuberculosis infection, the preferred regimen is 9 months of daily isoniazid (at least 270 doses), which provides over 90% efficacy when completed properly. 1

Standard Dosing Recommendations

Adults

• Daily regimen: 300 mg once daily for 9 months (minimum 270 doses) 2, 1
• Twice-weekly regimen: 900 mg twice weekly for 9 months (minimum 76 doses) under directly observed therapy (DOT) 2
• Completion is based on total doses administered, not calendar duration alone 2, 1

Children and Infants

• Daily dosing: 10-15 mg/kg/day as a single dose (maximum 300 mg) 3, 4
• Twice-weekly dosing: 20-40 mg/kg twice weekly (maximum 900 mg) under DOT 3
• For children, 9-12 months of isoniazid is recommended 1

Special Population Considerations

HIV-Infected Patients

HIV-infected adults should receive 9 months of daily isoniazid, with some guidelines recommending extension to 12 months for optimal protection. 2, 1, 5

• For patients on protease inhibitors or NNRTIs: 9-month isoniazid regimen (daily or twice-weekly) 2
• For patients NOT on protease inhibitors or NNRTIs: Alternative 2-month regimen of rifampin plus pyrazinamide (60 doses) may be used 2
• All HIV-infected patients receiving isoniazid should receive pyridoxine supplementation (25-50 mg daily or 50-100 mg twice weekly) to reduce neurologic side effects 1
• Recent meta-analysis demonstrates isoniazid preventive therapy with ART reduces tuberculosis risk (HR 0.68,95% CI 0.49-0.95) across all subgroups regardless of CD4 count or tuberculin skin test status 6

Pregnant Women

For pregnant women with HIV or at high risk, initiate the 9-month isoniazid regimen without delay, even during the first trimester. 2, 1, 5

• Pregnancy should not delay initiation or cause discontinuation of preventive therapy 2, 1
• Isoniazid is the only recommended option during pregnancy; rifampin-containing regimens are contraindicated 5

Contacts of Drug-Resistant TB

• Isoniazid-resistant, rifamycin-susceptible TB: 2 months of rifamycin plus pyrazinamide, or 4-6 months of rifamycin alone if pyrazinamide not tolerated 2, 5
• Multidrug-resistant TB: Despite resistance patterns, isoniazid preventive therapy still shows protective benefit (adjusted HR 0.19,95% CI 0.05-0.66) in contacts of MDR-TB patients 7

Alternative Shorter Regimens (Modern Updates)

While the provided guidelines focus on traditional 9-month isoniazid, newer evidence supports:

• 3 months of once-weekly isoniazid plus rifapentine (3HP): Preferred first-line for HIV-negative adults and children ≥2 years, with equivalent efficacy but higher completion rates 5
• 4 months of daily rifampin (4R): Preferred alternative with clinically equivalent effectiveness and lower toxicity 5

Monitoring Requirements

Monthly Clinical Evaluation

All persons on preventive therapy must receive monthly clinical assessment for adherence and side effects. 2, 1

• Assess for hepatitis symptoms (nausea, vomiting, abdominal pain, jaundice, dark urine) 1, 5
• For patients over 35 years: Obtain baseline transaminases, then monthly monitoring until completion 1
• For patients with suspected liver disorders, HIV infection, pregnancy, or chronic conditions: Baseline liver function tests required 5

Hepatotoxicity Considerations

• Grade 3+ toxicity (ALT/AST ≥5× ULN) occurs in approximately 8% of patients but resolves after cessation 8
• Critical caveat: Alcohol use does not appear to increase serious hepatotoxicity risk in patients without baseline liver enzyme elevations (≤2× ULN), challenging traditional contraindications 8
• Fatal hepatotoxicity occurs in approximately 8/1000 persons on 6-month regimens 9

Treatment Interruptions

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

• May continue original regimen to complete total required doses, or restart entire regimen 2
• Daily isoniazid: Extend up to 12 months if interruptions occur to ensure 270 total doses 2
• Twice-weekly isoniazid: Extend up to 12 months if interruptions occur to ensure 76 total doses 2

Critical Implementation Points

Directly Observed Therapy (DOT)

DOT must always be used with intermittent (twice-weekly) dosing regimens. 2, 5

• DOT is also recommended for 2-month preventive therapy regimens 2
• DOT is suggested for all children on TB prophylaxis 3

Pyridoxine Supplementation

• Recommended for malnourished patients and those predisposed to neuropathy (alcoholics, diabetics) 4
• Mandatory for all HIV-infected patients receiving isoniazid 1

Common Pitfalls to Avoid

• Never calculate completion by calendar time alone—count total doses administered 2, 1
• Never add a single drug to a failing regimen—always add at least 2 drugs to prevent resistance 5
• Never use rifapentine as monotherapy for preventive therapy 5
• Do not reflexively withhold isoniazid from alcohol users without baseline liver function assessment, as recent evidence shows safety in those with normal baseline enzymes 8