FDA updates carbidopa‑levodopa labeling after reports linking high doses to vitamin B6 deficiency and seizures

Lieutenant Commander Anne Tobenkin said DPV identified a case series of vitamin B6 deficiency‑associated seizures in patients receiving carbidopa‑levodopa that prompted regulatory action.

The review began with a FAERS report describing a 69‑year‑old man with an 11‑year history of Parkinson’s disease who developed polyneuropathy and persistent seizures while on oral carbidopa‑levodopa; laboratory testing showed markedly low vitamin B6, and seizures ceased after B6 supplementation. DPV searched FAERS and literature and identified 14 similar cases between 2014 and a September 2025 publication. "Based upon our review of the cases and medical literature, the multidisciplinary team concluded that there is reasonable evidence of a causal association between carbidopa‑levodopa products and vitamin B6 deficiency leading to seizures," Tobenkin said.

Most identified cases involved doses greater than 1,000 milligrams of levodopa per day, and two reports described seizures after a dose increase, which the team said may indicate a dose–severity relationship. Seven cases described administration of multiple anti‑seizure medications prior to recognition of B6 deficiency; two cases had fatal outcomes where seizures may have contributed, though autopsies were not completed. Tobenkin emphasized biological plausibility: carbidopa irreversibly binds the active form of vitamin B6 and levodopa metabolism uses B6 as a coenzyme.

DPV updated labeling for all carbidopa‑levodopa products to warn about the risk of vitamin B6 deficiency and seizures, describe a possible dose–severity relationship, note that such seizures may not respond to traditional anti‑seizure drugs, and recommend monitoring vitamin B6 levels before initiation and periodically during treatment. FDA also issued a drug safety communication summarizing the cases and the labeling change.

The presenters did not provide specific effective dates for the labeling changes in the session. Clinicians prescribing high daily doses of levodopa were advised to consider the updated label and monitor for symptoms consistent with vitamin B6 deficiency.