A 35-year-old man with newly diagnosed pulmonary tuberculosis is started on standard first-line antitubercular therapy. Which of the following is the most common adverse effect associated with isoniazid use?

Explanation

## Most Common Adverse Effect of Isoniazid **Key Point:** Peripheral neuropathy is the most frequent adverse effect of isoniazid, occurring in 10–20% of patients, particularly in slow acetylators and those with nutritional deficiencies. ### Mechanism of Isoniazid-Induced Neuropathy Isoniazid causes **pyridoxine (vitamin B₆) depletion** by: 1. Inhibiting pyridoxal kinase, the enzyme that activates pyridoxine 2. Increasing urinary excretion of pyridoxine metabolites 3. Reducing the availability of pyridoxal phosphate (the active cofactor for neurotransmitter synthesis) ### Risk Factors for Neuropathy - Slow acetylator phenotype (genetic polymorphism in NAT2) - Pre-existing nutritional deficiency (malnutrition, alcoholism, diabetes) - High-dose isoniazid (>5 mg/kg/day) - Prolonged duration of therapy ### Prevention and Management **High-Yield:** Routine pyridoxine supplementation (10–25 mg/day) is recommended for all patients on isoniazid, especially those at high risk. This is standard practice in TB programmes in India. ### Clinical Presentation - Distal, symmetrical, sensorimotor peripheral neuropathy - Paresthesias in feet and hands - Typically appears after 2–8 weeks of therapy - Reversible if caught early and pyridoxine is supplemented ### Comparison with Other Isoniazid Adverse Effects | Adverse Effect | Frequency | Mechanism | Preventable? | | --- | --- | --- | --- | | **Peripheral neuropathy** | 10–20% (most common) | Pyridoxine depletion | Yes (B₆ supplementation) | | Hepatotoxicity | 1–3% | Direct hepatocellular injury | Partial (baseline LFTs) | | Optic neuritis | <1% | Rare, idiosyncratic | No | | Hyperuricemia | <1% | Competitive renal tubular secretion | Partial (allopurinol) | **Clinical Pearl:** In Indian TB programmes, isoniazid-induced neuropathy is a common cause of treatment non-compliance if not anticipated. Prophylactic pyridoxine is cost-effective and prevents this complication entirely. **Warning:** Do not confuse isoniazid neuropathy with rifampicin-induced drug interactions or ethambutol optic neuritis — each has a distinct mechanism and prevention strategy.