DRUG
MECHANISM
TOXICITY
NOTES
Prodrug activated by mycobacterial catalase-peroxidase (KatG) → blocks mycolic acid synthesis (InhA)
Hepatitis (age, alcohol), peripheral neuropathy, sideroblastic anemia, seizures in overdose (B6), drug-induced lupus
Give pyridoxine · resistance: katG or inhA mutations · CYP inhibitor
Inhibits DNA-dependent RNA polymerase (rpoB)
Red-orange urine, tears, sweat (stains contacts); hepatitis; flu-like syndrome; thrombocytopenia
Potent CYP3A4 inducer → OCP failure, ↓ warfarin, ↓ protease inhibitors · monotherapy breeds resistance
Same class
Rifabutin: uveitis, less CYP induction
Rifabutin preferred with HIV protease inhibitors
Converted to pyrazinoic acid; works in acidic phagolysosomes
Hepatotoxicity, hyperuricemia → gout, arthralgia
Allows 6-month course
Blocks arabinosyl transferase → arabinogalactan
Optic neuritis: ↓ acuity, central scotoma, red-green color blindness
Baseline and monthly vision checks · renally dosed
Aminoglycoside (30S)
Ototoxicity, nephrotoxicity
Second-line / injectable
Resistant to INH + rifampin (± FQ)
Bedaquiline (ATP synthase; QT), pretomanid, linezolid, moxifloxacin
BPaL(M) regimens
Positive IGRA/PPD, normal chest X-ray, no symptoms
Rifampin 4 months (preferred), INH + rifapentine weekly × 12, or INH 6–9 months
Before TNF-α inhibitors, transplant
Macrolide-based
Clarithromycin or azithromycin + ethambutol ± rifabutin
Prophylaxis azithromycin (CD4 < 50, not on ART)
Folate synthesis inhibitor (like sulfonamides)
Hemolysis in G6PD deficiency, methemoglobinemia, agranulocytosis
Leprosy, Pneumocystis prophylaxis alternative, dermatitis herpetiformis
Binds mycobacterial DNA; anti-inflammatory
Red-brown skin discoloration
Lepromatous leprosy, erythema nodosum leprosum
Directly observed therapy
LFTs if risk factors; visual acuity (ethambutol); uric acid (PZA)
Stop drugs if ALT > 3–5× ULN