Alternative Treatments for Patients Unable to Tolerate Rifampicin and Isoniazid
For patients who cannot tolerate rifampicin and isoniazid, a regimen containing fluoroquinolones, ethambutol, and pyrazinamide for 9-12 months is the recommended alternative treatment. 1
Treatment Options Based on Drug Intolerance
When Both Rifampicin and Isoniazid Cannot Be Used:
- For drug-susceptible TB, a regimen containing pyrazinamide and ethambutol plus a fluoroquinolone (levofloxacin or moxifloxacin) is recommended for 9-12 months 1, 2
- The intensive phase should include at least 3-4 effective drugs, followed by a continuation phase with at least 3 drugs 2
- Treatment duration should be extended to at least 9-12 months total, with the exact duration depending on clinical response and extent of disease 1, 2
When Rifampicin Cannot Be Used but Isoniazid Is Tolerated:
- A regimen of isoniazid, ethambutol, pyrazinamide, and a fluoroquinolone for at least 12 months is recommended 1, 2
- This regimen has shown favorable outcomes in 80.7% of patients in real-world studies 2
When Isoniazid Cannot Be Used but Rifampicin Is Tolerated:
- Rifampicin, pyrazinamide, and ethambutol for 6-9 months is recommended 1, 3
- If pyrazinamide cannot be included, rifampicin and ethambutol should be given for at least 12 months 1
Specific Drug Recommendations
Fluoroquinolones:
- Levofloxacin or moxifloxacin should be included in regimens when rifampicin cannot be used 1, 4
- These are considered Group A drugs (strongly recommended) for MDR/RR-TB regimens and can be effectively used in drug-intolerant cases 1
Additional Agents to Consider:
- Bedaquiline may be included in regimens for patients aged ≥18 years when standard first-line drugs cannot be used 1
- Linezolid can be considered as part of the regimen, particularly in cases with extensive disease 1
- Clofazimine and cycloserine may be included as additional agents when options are limited 1
Management of Drug Reactions
- When reintroducing drugs after adverse reactions, a sequential approach should be used, starting with low doses and gradually increasing to full therapeutic doses 5
- For hepatotoxicity (the most common adverse reaction to rifampicin and isoniazid), monitor liver function tests until normalized before attempting any drug reintroduction 5, 2
- For severe hypersensitivity reactions like Stevens-Johnson syndrome, the offending drugs should be permanently excluded from the regimen 5
Special Populations
HIV Co-infection:
- In HIV-positive patients, drug interactions between antiretrovirals and TB medications must be carefully managed 1, 6
- Treatment duration may need to be extended and response should be closely monitored 1, 7
Pregnancy:
- Fluoroquinolones should be used with caution in pregnancy 1
- Ethambutol and pyrazinamide can generally be used safely during pregnancy 1
Monitoring and Follow-up
- Monthly clinical and laboratory monitoring is essential during treatment 1, 5
- Sputum cultures should be obtained regularly to confirm treatment response 2, 7
- Extended follow-up for at least 2 years after treatment completion is recommended to monitor for relapse 2