Pyridoxine Dosing with Anti-Tuberculosis Treatment
The recommended dose of pyridoxine (vitamin B6) with isoniazid-containing anti-tuberculosis treatment is 25-50 mg daily for prophylaxis in at-risk patients, and 100 mg daily for treatment of established peripheral neuropathy. 1
Standard Prophylactic Dosing
For patients at risk of neuropathy, administer pyridoxine 25-50 mg daily throughout the entire course of isoniazid therapy. 1
High-Risk Populations Requiring Prophylaxis
Pyridoxine supplementation is mandatory for the following groups receiving isoniazid: 1
- Pregnant women and breastfeeding infants
- HIV-infected persons
- Patients with diabetes mellitus
- Patients with alcoholism
- Malnourished patients
- Patients with chronic renal failure
- Elderly patients (advanced age)
- Patients on other neurotoxic medications
The CDC specifically recommends this 25-50 mg/day prophylactic dose for patients taking tuberculosis medications, emphasizing that it should only be increased to 100 mg/day if peripheral neuropathy actually develops. 2
Therapeutic Dosing for Established Neuropathy
If peripheral neuropathy develops despite prophylaxis or in patients not receiving prophylaxis, increase pyridoxine to 100 mg daily. 1
This higher therapeutic dose has been shown to reverse isoniazid-induced neuropathy in multiple case reports, with clinical improvement occurring within weeks to months. 3, 4 In severe cases with motor-dominant neuropathy, high-dose vitamin B6 injections can reduce long-term morbidity. 4
Clinical Context and Mechanism
Isoniazid causes pyridoxine deficiency by interfering with pyridoxal phosphate (the active coenzyme form), leading to peripheral neuropathy that typically manifests as burning feet and distal sensory impairment. 3, 5 The risk is substantially higher in slow acetylators of isoniazid, who may require dose reduction to 2.5-3 mg/kg/day in addition to pyridoxine supplementation. 3, 6
Historical studies from the Tuberculosis Chemotherapy Centre demonstrated that even the low prophylactic dose of 6 mg daily was effective in preventing neuropathy with high-dose isoniazid therapy (12.5-15.6 mg/kg), making the currently recommended 25-50 mg daily dose more than adequate for prevention. 7, 5
Important Caveats
Do not exceed 100 mg/day for routine supplementation, as the European Food Safety Authority sets the upper tolerable intake level at 100 mg/day for adults, and higher doses can paradoxically cause sensory neuropathy. 2
Continue pyridoxine throughout the entire duration of isoniazid therapy, not just during the intensive phase. 1
In pregnancy, prophylactic pyridoxine 10 mg/day is specifically recommended along with standard anti-tuberculosis treatment, though the standard 25-50 mg dose is also safe. 6
Monitor for neuropathy development even with prophylaxis, particularly in slow acetylators, as this may indicate need for isoniazid dose reduction in addition to increased pyridoxine. 3