What medications should be given to individuals receiving the HRZE (hrze: rifampicin, isoniazid, pyrazinamide, ethambutol) regimen for tuberculosis, particularly those with HIV co-infection or other co-morbidities?

Medications to Give with HRZE Regimen

All patients receiving HRZE (isoniazid, rifampicin, pyrazinamide, ethambutol) for tuberculosis must receive pyridoxine (vitamin B6) 25-50 mg daily to prevent isoniazid-induced peripheral neuropathy, particularly those with HIV co-infection who face compounded neuropathy risk. 1, 2

Essential Supplementation

• Pyridoxine (Vitamin B6) is mandatory for all HIV-infected patients receiving isoniazid-containing regimens at 25-50 mg daily, or 50-100 mg twice weekly for intermittent dosing 1
• HIV-infected persons are at particularly high risk for peripheral neuropathy, making pyridoxine supplementation non-negotiable in this population 1, 2
• The dose can be increased to 50-100 mg daily if neuropathy symptoms develop despite prophylaxis 1

Antiretroviral Therapy Timing and Selection (HIV Co-infection)

For HIV co-infected patients, antiretroviral therapy (ART) must be initiated within 2 weeks of starting TB treatment if CD4 <50 cells/μL, or within 8-12 weeks if CD4 ≥50 cells/μL, with critical attention to drug interactions. 2

Rifamycin Selection Based on ART Regimen

• Rifabutin must replace rifampicin when patients are taking protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) to avoid treatment failure of either HIV or TB 3, 2
• When rifabutin is used with indinavir, nelfinavir, or amprenavir, reduce the rifabutin dose from 300 mg to 150 mg daily 1
• When rifabutin is used with efavirenz, increase the rifabutin dose from 300 mg to 450 mg daily 1, 2
• The twice-weekly rifabutin dose remains 300 mg regardless of concurrent PI use 1

Critical ART Considerations

• Never interrupt antiretroviral therapy to accommodate rifampicin, as stopping ART increases mortality risk; instead switch to rifabutin-based regimens 3, 2
• For TB meningitis with HIV co-infection, delay ART initiation for 8 weeks due to increased risk of life-threatening immune reconstitution inflammatory syndrome (IRIS) 2

Opportunistic Infection Prophylaxis (HIV Co-infection)

• Continue trimethoprim-sulfamethoxazole (TMP-SMZ) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis if CD4 <200 cells/μL, as it does not interact with TB medications 1
• TMP-SMZ also provides protection against toxoplasmosis and certain bacterial infections 1
• Mycobacterium avium complex (MAC) prophylaxis with azithromycin is preferred over clarithromycin during pregnancy and can be continued with HRZE 1

Corticosteroids for Specific TB Manifestations

• For CNS tuberculosis (tuberculous meningitis), add adjunctive corticosteroids which improve outcomes in moderate to severe disease (Stages II and III) 4
• For severe IRIS, consider prednisone 1-2 mg/kg/day for 1-2 weeks, then taper 2
• Mild IRIS can be managed with nonsteroidal anti-inflammatory drugs 2

Monitoring Requirements

• Implement directly observed therapy (DOT) for all HIV-TB co-infected patients to ensure adherence and prevent drug resistance 2
• Monitor liver function tests regularly due to overlapping hepatotoxicity from multiple medications, especially during the first 2 months 2, 4
• Check sputum microscopy and culture at 2 months to assess treatment response 2
• Monitor CD4 count and HIV viral load every 3 months 2

Critical Pitfalls to Avoid

• Never use rifampicin with protease inhibitors or NNRTIs without switching to rifabutin, as this causes treatment failure of either HIV or TB 3
• Never omit pyridoxine in HIV-infected patients receiving isoniazid, as the risk of peripheral neuropathy is substantially elevated 1, 2
• Never delay TB treatment to accommodate other medications, as TB treatment is the immediate priority for mortality reduction 3
• Never add a single drug to a failing regimen, as this creates acquired resistance 3, 4

Special Populations

Pregnancy

• Continue the standard HRZE regimen, as benefits outweigh potential risks 2
• Pyridoxine 10 mg/day is recommended prophylactically 5
• Azithromycin is preferred over clarithromycin for MAC prophylaxis due to teratogenicity concerns 1

Renal Failure

• Adjust doses of ethambutol and streptomycin according to creatinine clearance 5
• No modifications needed for isoniazid, rifampicin, or pyrazinamide doses when used with standard antiretrovirals 1

Diabetes Mellitus

• Use the same HRZE regimen as non-diabetic patients 5
• Increase doses of oral hypoglycemic agents due to rifampicin-induced metabolism 5
• Prophylactic pyridoxine is indicated 5