Should a patient on Keppra (Levetiracetam) supplement with Vitamin B-6?

Vitamin B6 Supplementation with Levetiracetam (Keppra)

Routine vitamin B6 supplementation is not recommended for patients taking Keppra unless they have specific risk factors for deficiency or develop symptoms of neuropathy.

Evidence-Based Rationale

Levetiracetam does not have the same mechanism of vitamin B6 depletion as medications like isoniazid or carbidopa-levodopa. Unlike these drugs, Keppra does not act as a B6 antagonist or irreversibly bind to pyridoxal 5'-phosphate (PLP), the active form of vitamin B6 1. The primary medications requiring routine B6 supplementation are tuberculosis drugs (isoniazid) and carbidopa-levodopa in high doses 2, 3.

When B6 Supplementation IS Indicated

Consider B6 supplementation in Keppra patients who have:

• Pre-existing risk factors for B6 deficiency including pregnancy, breastfeeding, HIV infection, diabetes, alcoholism, malnutrition, chronic renal failure, or advanced age 2
• Chronic kidney disease or dialysis, as these patients have increased B6 requirements and losses 2
• Concurrent medications that deplete B6, such as isoniazid, penicillamine, anticonvulsants (other than Keppra), or corticosteroids 4
• Symptoms of B6 deficiency including peripheral neuropathy, numbness/paresthesia in extremities, loss of distal sensation, motor ataxia, or weakness 4

Safe Dosing When Supplementation is Needed

If supplementation is warranted:

• Standard supplementation: 25-50 mg/day for at-risk patients 2, 5
• For established peripheral neuropathy: Increase to 100 mg/day 2
• Preferred formulation: PLP-based supplements administered weekly (50-100 mg) rather than daily to minimize neurotoxicity risk 6
• Target plasma PLP level: 30-60 nmol/L (7.4-15 μg/L) 6

Critical Safety Considerations

Avoid excessive B6 intake, as toxicity can paradoxically cause the same neurological symptoms as deficiency:

• Upper tolerable limit: 100 mg/day for adults 5
• Toxicity threshold: Neurological damage reported at doses >100 mg/day long-term, with severe toxicity at >500 mg/day 7, 8
• Toxicity symptoms: Sensory neuropathy, ataxia, loss of deep tendon reflexes, and peripheral nerve damage that may persist even after discontinuation 4
• Washout period: 20-40 days required for complete clearance if toxicity occurs 8

Monitoring Recommendations

For patients requiring B6 supplementation:

• Baseline measurement: Check plasma PLP level before starting supplementation 4
• Follow-up: Recheck levels 3-6 months after initiating supplementation 4
• Ongoing monitoring: Annual monitoring once levels normalize in stable patients 4
• High-risk patients (CKD, dialysis): Monitor every 3 months until stabilization 4
• Target range: Maintain plasma PLP between 30-60 nmol/L to avoid both deficiency and toxicity 6

Common Pitfalls to Avoid

• Do not routinely supplement all Keppra patients without assessing individual risk factors, as this exposes patients to unnecessary toxicity risk 5, 8
• Do not use high-dose daily B6 (>100 mg/day) without documented deficiency and monitoring, as this increases neurotoxicity risk 5, 4
• Do not confuse Keppra with carbidopa-levodopa, which does require B6 monitoring due to irreversible PLP binding 3
• Do not supplement B6 for cognitive benefits in dementia patients, as this is not evidence-based and may cause harm 2