A common drug combo for Parkinson’s disease will require a new FDA warning after the agency flagged 14 cases of seizures in patients using the medications.
The agency is mandating (PDF) that drugmakers marketing products incorporating levodopa and carbidopa update their prescribing information to note that the drugs can cause vitamin B6 deficiency and vitamin B6 deficiency-associated seizures. Healthcare providers should evaluate patients’ baseline vitamin B6 levels prior to and during treatment and supplement patients with the vitamin as necessary, the warning says.
The label update affects Amneal’s Crexont and Rytary; Avion Pharmaceuticals’ Dhivy; Merck’s Sinemet and controlled-release Sinemet CR; Novartis’ Stalevo; and AbbVie’s Duopa. Also affected is AbbVie’s newer Vyalev, a subcutaneous treatment that delivers prodrugs of carbidopa and levodopa via an infusion pump system. Vyalev’s ingredients of foscarbidopa and foslevodopa are drug derivatives of carbidopa and levodopa that become active after entering the body.
Parkinson’s disease has been linked to dopamine deficiency, making levodopa, a metabolic precursor to dopamine, a favored treatment approach dating back to the 1960s. However, the drug must be taken with another medication to prevent it from breaking down in the bloodstream before crossing the blood-brain barrier, making the combo of carbidopa and levodopa the reigning standard-of-care in Parkinson’s disease treatment.
But as levodopa converts to dopamine, crucial vitamin B6 levels can be impacted, the FDA pointed out in its warning. Carbidopa also binds to the active form of the vitamin, which can further drive down vitamin B6 levels.
In its safety review, the FDA identified 14 causes of seizures linked to vitamin B6 deficiency in patients taking the common Parkinson’s disease drugs, including 13 instances that were submitted to the FDA’s adverse events reporting system and 1 reported in medical literature. There are “likely additional cases about which we were unaware,” the agency notes.
Each of the reviewed cases involved levodopa doses greater than 1,000 mg daily and the seizures were split across oral formulations of the drugs and an enteral suspension. AbbVie makes the enteral suspension version with its Duopa, a gel medication that’s delivered directly into the small intestine through a tube.
Some of the cases progressed to status epilepticus, a longer-lasting seizure that can cause brain damage or death, the FDA added. Several of the seizure reports showed “clinical evidence supportive of vitamin B6 deficiency,” and nine seizures were resolved when treated with supplemental vitamin B6. Two deaths occurred in patients with “documented low vitamin B6 levels and poorly controlled seizures,” according to the agency.
“Based on the available data, FDA concluded there is reasonable evidence of a causal association between drug products containing carbidopa/levodopa and vitamin B6 deficiency-associated seizures,” the FDA said.
Although no seizures were confirmed to result from products containing carbidopa/levodopa and entacapone (Novartis’ Stalevo) and injectable versions of carbidopa/levodopa (AbbVie’s Vyalev), the FDA is slapping the same warning on those meds, considering a likely risk based on “biological plausibility” and clinical trial data from the meds.
Vyalev was the most recently approved carbidopa/levodopa med, scoring its FDA nod in 2024. The drug is a follow-up to AbbVie’s landmark 2015 Duopa, which sparked a trend of delivery system innovation in the Parkinson’s space as manufacturers looked to avoid the short half-life associated with oral versions of the meds.
The FDA safety sweep of carbidopa and levodopa meds could lend credence to Supernus Pharmaceuticals’ novel Parkinson’s disease approach with Onapgo, a wearable pump that delivers a continuous subcutaneous infusion of Supernus’ dopamine agonist apomorphine (Apokyn). After winning approval in 2025 following three FDA rejections, the drug made so much of a splash in the disease space that the company had to pause delivery to new patients in November based on “stronger than expected demand,” Supernus said.
Onapgo’s shipments has since resumed and the drug collected $17.3 million in 2025 sales, while AbbVie’s Vyalev took home $482 million and its older Duopa garnered sales of $381 million.