When Anti-Tubercular Drugs Are Not Given
Anti-tubercular drugs should be temporarily withheld when severe hepatotoxicity develops (AST/ALT ≥5 times normal or rising bilirubin), when severe drug hypersensitivity reactions occur, or in specific clinical scenarios where the risks of treatment outweigh benefits until the condition is corrected. 1
Primary Scenarios for Withholding Anti-TB Drugs
Severe Hepatotoxicity
- If AST/ALT rises to 5 times normal or bilirubin rises, rifampicin, isoniazid, and pyrazinamide must be stopped immediately. 1
- After stopping hepatotoxic drugs, if the patient is not unwell and tuberculosis is non-infectious, no treatment needs to be given until liver function returns to normal. 1
- If the patient is unwell or sputum smear positive, streptomycin and ethambutol should be used as bridging therapy until liver function normalizes. 1
- Once liver function normalizes, drugs can be reintroduced sequentially: isoniazid first (starting 50 mg/day, increasing to 300 mg/day over 2-3 days), then rifampicin (75 mg/day increasing to full dose), then pyrazinamide last (250 mg/day increasing to full dose). 1
Drug Intolerance Requiring Alternative Regimens
- Fluoroquinolones should not be used as first-line agents for drug-susceptible tuberculosis except when patients are intolerant of first-line drugs. 1
- When first-line agents cannot be used due to intolerance, levofloxacin is the preferred oral alternative for treating tuberculosis caused by organisms presumed sensitive to fluoroquinolones. 1
Specific Drug Contraindications
Pregnancy-Related Restrictions:
- Fluoroquinolones should be avoided in pregnancy due to teratogenic effects. 1
- Streptomycin should not be given during pregnancy due to ototoxicity to the fetus. 2
Renal Insufficiency:
- Streptomycin and ethambutol should be avoided if possible in renal failure, but if used, serum drug concentrations must be monitored and doses substantially reduced unless dialysis is used. 1
- Para-aminosalicylic acid (PAS) is contraindicated in severe renal insufficiency unless there is no alternative, due to accumulation of the acetylated form. 1
Hepatic Disease:
- In patients with pre-existing liver disease, pyrazinamide should not be given if underlying liver test abnormalities exist. 3
- Patients with stable liver disease but normal liver enzymes can receive all anti-tuberculous drugs, but require frequent monitoring of liver function tests. 2
Visual Monitoring Limitations:
- Ethambutol is generally not recommended for routine use in children whose visual acuity cannot be monitored (typically less than 5 years of age), unless there is concern for resistance to isoniazid or rifampicin. 1
Critical Clinical Pitfalls to Avoid
- Never discontinue rifampicin or other first-line drugs because of minor gastrointestinal side effects in the first few weeks of therapy. 4 Gastrointestinal upset is common early in treatment but does not warrant stopping first-line agents. 5
- Single-drug treatment of active tuberculosis with isoniazid or any other medication is inadequate therapy and must never be used. 6 This prevents emergence of drug resistance. 6
- Do not withhold necessary bronchodilator or inhaled corticosteroid therapy out of concern about "masking TB symptoms" or interfering with treatment, as these medications address different pathophysiology. 5
Monitoring Requirements Before Withholding Drugs
- Baseline liver function should be checked before treatment for clinical cases. 1
- Regular monitoring of liver function (weekly for two weeks, then two-weekly for first two months) is required for patients with known chronic liver disease. 1
- For patients with normal pre-treatment liver function, regular monitoring is not required, but liver function should be repeated if fever, malaise, vomiting, jaundice, or unexplained deterioration occur. 1
- Renal function should be checked before treatment with streptomycin or ethambutol. 1
- Baseline visual acuity testing (Snellen chart) and color discrimination (Ishihara tests) should be performed before ethambutol use. 1