Which anti-TB drug is commonly associated with peripheral neuropathy, mitigated by pyridoxine?

• A. Rifampin
• B. Ethambutol
• C. Isoniazid
• D. Pyrazinamide

Answer: (C)

Peripheral neuropathy is a classic adverse effect of isoniazid because the drug can cause pyridoxine (vitamin B6) deficiency. Isoniazid interferes with the body's ability to activate pyridoxine to its active form, pyridoxal-5'-phosphate, and it can also form an inactive complex with this cofactor. Without enough active vitamin B6, nerves don’t get the necessary cofactors for neurotransmitter synthesis and myelin maintenance, leading to numbness, tingling, and weakness, especially in a symmetric distal distribution. To prevent this toxicity, pyridoxine supplementation is routinely given with isoniazid-containing regimens. The other anti-TB drugs have different toxicity profiles—rifampin commonly causes hepatotoxicity and drug interactions; ethambutol can cause optic neuritis; pyrazinamide may cause hyperuricemia and hepatotoxicity—so peripheral neuropathy tied to vitamin B6 deficiency is most characteristic of isoniazid.