What is the recommended prophylaxis medication for individuals exposed to tuberculosis (TB)?

TB Prophylaxis for Exposed Individuals

For individuals exposed to tuberculosis, the preferred prophylaxis regimens are 3 months of once-weekly isoniazid plus rifapentine OR 4 months of daily rifampin, both of which offer superior completion rates and safety compared to traditional isoniazid monotherapy. 1

Preferred Regimens (in order of preference)

First-Line Options

• 3 months of once-weekly isoniazid (900 mg) plus rifapentine is the preferred regimen for latent TB infection, demonstrating equivalent effectiveness to 9 months of isoniazid with significantly higher completion rates and less hepatotoxicity in HIV-negative persons 1
• 4 months of daily rifampin (10 mg/kg, maximum 600 mg) is equally preferred, particularly suitable when isoniazid cannot be tolerated or when drug interactions with rifapentine are problematic 1, 2

Alternative Regimens When Preferred Options Cannot Be Used

• 2 months of daily isoniazid plus rifampin is an acceptable alternative for both HIV-negative and HIV-positive adults and children, with similar effectiveness to longer isoniazid courses 3
• 6-9 months of daily isoniazid (300 mg for adults, 10 mg/kg for children) remains an alternative when rifamycin-based regimens cannot be used 3, 1

Critical Pre-Treatment Requirements

Rule Out Active TB Disease First

• Active tuberculosis must be excluded before initiating prophylaxis through clinical evaluation, chest radiography, and sputum examination if symptomatic 1, 2
• This is the most critical pitfall—treating active TB with prophylaxis regimens leads to drug resistance 2

Baseline Assessment

• Obtain tuberculin skin test (TST) or interferon-gamma release assay (IGRA) to document latent infection 3
• Baseline liver function tests (AST/ALT, bilirubin) are required for patients with pre-existing liver disease, HIV infection, pregnancy, heavy alcohol use, or history of liver injury 1
• Monthly clinical evaluation is mandatory for all patients to assess adherence and detect adverse effects 1

Special Population Considerations

HIV-Infected Individuals

• Use the same preferred regimens (3 months isoniazid-rifapentine or 4 months rifampin) 1
• For HIV-infected children, a 12-month isoniazid regimen is recommended by the American Academy of Pediatrics 1
• Critical drug interaction warning: Rifamycins cannot be used with protease inhibitors, NNRTIs including ritonavir, hard-gel saquinavir, or delavirdine 1
• For HIV-positive persons with negative TST or anergy, 6 months of daily isoniazid is conditionally recommended 3

Pregnant Women

• Do not delay prophylaxis based on pregnancy alone, particularly for recent converters or HIV-infected women 1
• The 9-month isoniazid regimen is the only recommended option during pregnancy 1
• Rifapentine safety data in pregnancy are insufficient; avoid this regimen 1
• Add pyridoxine 25-50 mg daily to prevent peripheral neuropathy 4

Healthcare Workers and Recent Converters

• Healthcare workers with positive PPD results who are recent converters, close contacts of active TB cases, have medical conditions increasing TB risk, have HIV infection, or use injection drugs should receive preventive therapy regardless of age 3
• For those without these risk factors, consider preventive therapy if under 35 years of age 3

High-Risk Medical Conditions Requiring Prophylaxis

• Recent TB infection (within 2 years) 3
• Silicosis or chest radiograph showing inactive fibrotic lesions: consider 4 months of isoniazid plus rifampin or 12 months of isoniazid 3
• Close contacts of infectious TB patients, even if anergic 3

Monitoring and Safety

Monthly Clinical Evaluation Requirements

• Assess for fever, malaise, nausea, vomiting, abdominal pain, jaundice, or dark urine 3, 1
• Review adherence and address barriers to completion 1
• For patients >35 years old or with risk factors for hepatotoxicity (daily alcohol use, chronic liver disease, injection drug use), obtain monthly transaminase measurements 3

When to Stop Treatment

• Discontinue immediately if transaminases exceed 3-5 times the upper limit of normal 3
• Stop if clinical signs of hepatitis develop regardless of laboratory values 3

Treatment Completion Criteria

• Completion is based on total doses administered, not duration alone 1
• For 9-month isoniazid: at least 270 doses over 9-12 months (allowing for interruptions) 1
• For 3-month isoniazid-rifapentine: 12 directly observed doses 1
• For 4-month rifampin: at least 120 daily doses 1

Critical Drug Interactions and Contraindications

Rifamycin Interactions

• Rifampin significantly reduces levels of oral contraceptives, anticoagulants, and many other medications—review all medications before prescribing 2
• Cannot use with certain antiretrovirals (see HIV section above) 1
• Rifampin should be taken 1 hour before or 2 hours after meals with a full glass of water 2

Isoniazid Precautions

• Higher hepatotoxicity risk in persons >35 years, daily alcohol users, postpartum women, and those with chronic liver disease 3
• Postpubertal Black and Hispanic women may have greater hepatitis risk 3

Suspected Multidrug-Resistant TB Exposure

• For persons likely exposed to MDR-TB, alternative multidrug preventive therapy regimens should be considered in consultation with TB specialists 3
• Standard prophylaxis regimens are inadequate for MDR-TB exposure 3

Post-Treatment Follow-Up

• No routine follow-up is required after completing treatment unless the patient develops TB symptoms or is re-exposed to infectious TB 1
• Counsel patients that they can be reinfected with another strain of M. tuberculosis despite completing prophylaxis 3