In a 40-year-old man with pulmonary tuberculosis on standard anti‑tuberculosis therapy for three months who developed peripheral neuropathy after stopping pyridoxine (vitamin B6) supplementation, which drug is responsible for the neuropathy?

Isoniazid is Responsible for the Peripheral Neuropathy

The answer is D - Isoniazid. This patient's peripheral neuropathy (pins and needles, numbness in hands and feet) developed after discontinuing pyridoxine (vitamin B6) supplementation, which is the classic presentation of isoniazid-induced peripheral neuropathy.

Mechanism and Clinical Presentation

Isoniazid causes peripheral neuropathy by interfering with pyridoxine metabolism, leading to vitamin B6 deficiency. The neuropathy typically manifests as:

• Paresthesias (pins and needles sensation) in distal extremities
• Numbness in hands and feet
• Loss of distal sensation
• Motor weakness in severe cases

The temporal relationship with stopping pyridoxine is pathognomonic for isoniazid-induced neuropathy 1, 2, 3.

Prevention and Management

Prophylactic Pyridoxine Supplementation

Multiple authoritative guidelines consistently recommend pyridoxine supplementation with isoniazid therapy 2, 3, 2:

• Standard prophylactic dose: 25-50 mg/day for all patients at risk
• Higher-risk populations requiring supplementation:
  • Pregnant women and breastfeeding infants
  • Persons with HIV infection
  • Patients with diabetes mellitus
  • Alcoholism
  • Malnutrition or chronic renal failure
  • Advanced age
  • Pre-existing seizure disorders

Treatment of Established Neuropathy

For patients who develop peripheral neuropathy 4, 3:

1. Increase pyridoxine to 100 mg/day for symptomatic relief
2. If mild: Continue isoniazid with increased pyridoxine supplementation
3. If severe or persistent despite increased pyridoxine: Stop isoniazid immediately

Why Not the Other Drugs?

• Pyrazinamide (A): Causes hyperuricemia and arthralgia, not peripheral neuropathy 1, 5
• Ethambutol (B): Causes optic neuritis (retrobulbar neuritis), not peripheral neuropathy 5
• Rifampicin (C): Causes hepatotoxicity, flu-like syndrome, and drug interactions, but not peripheral neuropathy 1, 5

Clinical Pearls

Peripheral neuropathy from isoniazid is uncommon at standard doses (5 mg/kg) but becomes clinically significant when pyridoxine supplementation is omitted in at-risk patients 1. The fact that this patient's symptoms began specifically after stopping his vitamins (pyridoxine) confirms the diagnosis.

Immediate action required: Restart pyridoxine at 100 mg/day and reassess symptoms. If neuropathy is severe or doesn't improve, consider substituting isoniazid with an alternative agent after consultation with TB specialists 4.