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July 22, 2026
As of March 2026, the U.S. Food and Drug Administration (FDA) requires updated labeling for all carbidopa-levodopa products to warn about vitamin B6 deficiency and associated seizures based on a review of 14 cases. All cases involved levodopa doses >1,000 mg/day, some progressed to status epilepticus refractory to standard anticonvulsants, and two fatalities occurred. The limited number of reports likely underestimates real-world risk since many of the neurologic symptoms that serve as warning signs are nonspecific and, in hospice, they’re commonly attributed to disease progression.
What causes B6 deficiency?
Risk factors for vitamin B6 deficiency include inadequate dietary intake, malabsorption (e.g., related to Crohn’s disease, celiac disease, or gastric surgery), chronic inflammation, smoking, dialysis, and the use of certain medications (the most clinically significant cause). In the case of carbidopa-levodopa, some B6 is consumed during levodopa metabolism and a larger portion is irreversibly bound and deactivated by carbidopa. Other drugs associated with B6 deficiency include isoniazid, hydralazine, certain antiepileptics (phenytoin, valproic acid, and carbamazepine), and some anticancer drugs (including vincristine).
The FDA’s call to action
The warning advises clinicians to assess vitamin B6 levels before starting therapy, monitor levels during treatment, and consider supplementation when appropriate.
What hospice clinicians can do
Since carbidopa-levodopa is often continued indefinitely and hospice patients could be particularly vulnerable to developing B6 deficiency, we suggest the following:
Monitor for symptoms of B6 deficiency. Sounds easy enough, but in the hospice population it’s nearly impossible to parse out from underlying disease progression. Still, keep these on your radar:
Consider empiric supplementation in high-risk or symptomatic patients (low risk, low cost), especially those taking >1,000mg levodopa per day. There’s not a clear recommendation as far as which dose to use. UpToDate editors recommend a daily multivitamin for all patients on chronic levodopa. Most standard adult multivitamins contain 2-3mg of B6 and while that might be enough to prevent a problem from developing, it’s unlikely to be sufficient for patients who have an actual deficiency—in those cases you’ll want to use 50 mg/day. A recently published JAMA article cites 50mg/day as a replacement dose for patients taking medications known to cause B6 deficiency (including levodopa). Sensory neuropathy has been reported when 50mg doses are taken for longer than 6 months, but most hospice patients won’t be exposed long enough if it’s started after hospice election and the risk of undertreating deficiency outweighs the risk of short-term supplementation.
Our take:
Given the realities of hospice care (limited lab monitoring, declining nutritional intake, and the difficulty of distinguishing B6 deficiency symptoms from disease progression) we recommend a tiered approach:
| No symptoms of vitamin B6 deficiency and levodopa doses <1,000mg/day | Mild symptoms of vitamin B6 deficiency or levodopa dose ≥1,000mg/day | Seizures |
|---|---|---|
| Supplement with standard adult multivitamin | Supplement with oral vitamin B6 50mg/day | Urgent B6 administration is indicated; after acute episode is managed, start daily supplementation to prevent recurrence |
While we’ve recommended what we believe are reasonable doses of B6, there isn’t an exact science to determining the right dose, especially in the absence of routine lab monitoring. But in hospice, where our patients are among the most vulnerable to nutritional deficiencies and where new neurologic symptoms are too easily chalked up to disease progression, a proactive approach to B6 supplementation is a small step that could prevent a serious and entirely treatable complication. A daily multivitamin costs pennies. A bottle of pyridoxine 50 mg tablets costs a few dollars. The cost of missing a preventable seizure is immeasurably higher.
Written by: OnePoint Patient Care Clinical Team