Vitamin B6 (Pyridoxine) Dosing with HRZE Therapy
Pyridoxine (vitamin B6) should be given at a dose of 25-50 mg daily to all persons at risk of neuropathy when receiving HRZE therapy, and the dose should be increased to 100 mg daily for patients who develop peripheral neuropathy. 1
Standard Dosing Recommendations
For Prevention of Neuropathy:
- Standard preventive dose: 25-50 mg daily 1, 2
- For intermittent dosing regimens: 50-100 mg twice weekly 1
For Treatment of Established Neuropathy:
Risk Factors Requiring Pyridoxine Supplementation
Pyridoxine supplementation is indicated for all patients with the following risk factors:
- Pregnant women
- Breastfeeding mothers
- Persons with HIV infection
- Patients with diabetes
- Alcoholism
- Malnutrition
- Chronic renal failure
- Advanced age 1, 2
Mechanism and Rationale
Isoniazid (INH), a key component of HRZE therapy, interferes with pyridoxine metabolism by:
- Competitively inhibiting pyridoxine's action in metabolic functions 3
- Causing reduction in glutamic-oxaloacetic transaminase (GOT) activity 4
- Leading to deficiency of both coenzyme (pyridoxal phosphate) and apoenzyme 4
This interference can result in peripheral neuropathy, characterized by:
- Initial symptoms of burning feet 5
- Paresthesia
- Distal sensory impairment that may extend proximally
- Loss of deep tendon reflexes
Duration of Supplementation
Pyridoxine supplementation should be continued for the entire duration of anti-TB therapy containing isoniazid 2.
Special Considerations
Dosing Based on Acetylator Status:
- Slow inactivators of isoniazid are at higher risk of developing peripheral neuropathy 6, 4
- Consider measuring acetylator status if symptoms develop, and potentially reducing isoniazid dose to 3 mg/kg/day or less in slow acetylators 5
Safety Concerns:
- Long-term high-dose supplementation (>500 mg/day) can cause sensory neuropathy 2
- Even doses as low as 100 mg/day have been associated with Lhermitte signs (spinal cord effects) with long-term use 2
- Symptoms of toxicity include sensory neuropathy with ataxia, areflexia, impaired sensations, and dermatologic lesions 2
Cost Considerations
In resource-limited settings, even low-dose pyridoxine (6 mg daily) has been shown to be effective in preventing peripheral neuropathy in patients receiving high-dose isoniazid 6, 4. This makes prophylaxis feasible even in developing countries.
Monitoring
If peripheral neuropathy develops despite prophylaxis, consider:
- Increasing pyridoxine dose to 100 mg daily 1, 2
- Evaluating for slow acetylator status 5
- Potentially reducing isoniazid dose if appropriate 5
By following these guidelines for pyridoxine supplementation, the risk of isoniazid-induced peripheral neuropathy can be significantly reduced while maintaining the effectiveness of HRZE therapy for tuberculosis.