What is the principal risk of LONG-TERM isoniazid therapy?

Correct answer: B. Hepatotoxicity (drug-induced hepatitis)

• A. ❌ Nephrotoxicity is characteristic of aminoglycosides, amphotericin B and vancomycin — not isoniazid.
• B. ✅ CORRECT — HEPATOTOXICITY is isoniazid's dose- and duration-related major adverse effect, with risk rising sharply after age 35 and with concurrent alcohol use or rifampin. Liver enzymes are monitored throughout therapy.
• C. ❌ Pulmonary fibrosis is associated with bleomycin, amiodarone and methotrexate.
• D. ❌ Ototoxicity belongs to aminoglycosides (streptomycin, in TB regimens) and to loop diuretics.

Note: Isoniazid also causes peripheral neuropathy by antagonizing pyridoxine — vitamin B6 is co-prescribed. Rifampin turns secretions orange-red; ethambutol → optic neuritis; pyrazinamide → hyperuricemia.