Isoniazid Requires Vitamin B6 Supplementation
Isoniazid (INH) is the medication that requires vitamin B6 (pyridoxine) supplementation to prevent peripheral neuropathy. 1
Mechanism and Rationale
Isoniazid competitively inhibits pyridoxine's role in essential metabolic functions, including protein, carbohydrate, and fatty acid metabolism, as well as brain amine synthesis. 2 This interference can lead to peripheral neuropathy, particularly in slow inactivators of isoniazid who are at significantly higher risk. 3, 4
Standard Dosing Recommendations
Prophylactic Supplementation
- Standard dose: 25-50 mg daily for all at-risk patients receiving isoniazid 1
- This applies to both active tuberculosis treatment and latent TB infection therapy 1, 5
High-Risk Populations Requiring B6 Supplementation
The following groups must receive pyridoxine with isoniazid therapy 1, 6:
- Pregnant women
- Breastfeeding infants
- Persons with HIV infection
- Patients with diabetes mellitus
- Patients with alcoholism
- Malnourished patients
- Patients with chronic renal failure
- Patients of advanced age
Treatment Dose for Established Neuropathy
Clinical Evidence
A landmark study from the Tuberculosis Chemotherapy Centre demonstrated that 6 mg daily pyridoxine prevented peripheral neuropathy in patients receiving high-dose isoniazid (12.5-15.6 mg/kg), with significant increases in vitamin B6 concentrations and glutamic-oxaloacetic transaminase (GOT) activity. 3 The neuropathy occurred predominantly in slow inactivators and was associated with substantial reductions in GOT activity. 3
Special Considerations
Isoniazid Overdose
In acute isoniazid toxicity (doses >30 mg/kg), pyridoxine becomes a life-saving antidote administered in gram-per-gram amounts equal to the isoniazid ingested, as it eliminates refractory seizure activity and corrects metabolic acidosis. 8
Pediatric Populations
One study suggested vitamin B6 supplementation may be unnecessary in childhood tuberculosis, as no neurological complications occurred in either supplemented or placebo groups. 9 However, current guidelines still recommend supplementation for high-risk pediatric patients (breastfeeding infants, malnourished children). 1
Other TB Medications
No other first-line tuberculosis medications require routine vitamin B6 supplementation. Rifampin, rifabutin, rifapentine, pyrazinamide, and ethambutol do not necessitate pyridoxine co-administration. 1
Practical Implementation
- Administer pyridoxine concurrently with each isoniazid dose 5
- For directly observed therapy (DOT) regimens given 5 days weekly, adjust pyridoxine dosing to match (50-100 mg twice weekly for twice-weekly DOT) 1
- Monitor for signs of peripheral neuropathy: numbness, paresthesias in extremities, loss of distal sensation, or loss of deep tendon reflexes 10
Critical Warning
Do not exceed 100 mg/day pyridoxine for routine supplementation, as chronic high-dose vitamin B6 (>100 mg/day) paradoxically causes toxic sensory neuropathy. 10, 7, 6 The upper tolerable intake level is 100 mg/day for adults. 7