A new warning about a common combination drug for Parkinson’s disease is needed after the FDA reported 14 seizures in patients taking the drug.
The agency requires drug companies that sell products that incorporate levodopa and carbidopa to update their prescribing information to clearly state that these drugs can cause vitamin B6 deficiency or seizures related to vitamin B6 deficiency (PDF). Healthcare providers should assess patients’ baseline vitamin B6 levels before and during treatment and supplement patients with the vitamin as needed, the alert states.
The label update affects Amneal’s Crexont and Rytary. Dhivy from Avion Pharmaceuticals. Merck’s Sinemet and controlled-release Sinemet CR. Novartis Starevo. and AbbVie’s Duopa. AbbVie’s new Biyalev is also affected. It is a subcutaneous treatment that delivers prodrugs of carbidopa and levodopa via an infusion pump system. Byarev’s foscarbidopa and foslevodopa ingredients are drug derivatives of carbidopa and levodopa that become active when they enter the body.
Because Parkinson’s disease is associated with dopamine deficiency, levodopa, the metabolic precursor of dopamine, has been the treatment of choice since the 1960s. However, this drug must be taken with another drug to prevent it from being broken down in the bloodstream before it crosses the blood-brain barrier, making the combination of carbidopa and levodopa the most likely standard of care in treating Parkinson’s disease.
However, when levodopa is converted to dopamine, important vitamin B6 levels may be affected, the FDA noted in the warning. Carbidopa also binds to the active form of the vitamin, which can further reduce vitamin B6 levels.
During its safety review, the FDA identified 14 cases of seizure causes related to vitamin B6 deficiency in patients taking common Parkinson’s disease drugs, including 13 cases submitted to the FDA’s adverse event reporting system and one case reported in the medical literature. The agency notes that “there may be additional incidents of which we were not aware.”
Each case reviewed involved a daily levodopa dose of >1,000 mg, and the attacks were divided into oral formulations and enteral suspensions. AbbVie makes an enteral suspension version of Duopa, a gel drug that is delivered directly to the small intestine through a tube.
Some cases progress to status epilepticus, prolonged seizures that can cause brain damage and death, the FDA added. Some of the seizure reports showed “clinical evidence supporting vitamin B6 deficiency,” and nine of the seizures resolved when treated with vitamin B6 supplementation. Two deaths occurred in patients with “low vitamin B6 levels and evidence of poor seizure control,” the agency said.
“Based on the available data, FDA has concluded that there is reasonable evidence of a causal relationship between medicines containing carbidopa/levodopa and seizures associated with vitamin B6 deficiency,” the FDA said.
Although no seizures have been confirmed with products containing carbidopa/levodopa and entacapone (Novartis’ Starevo) or the injectable version of carbidopa/levodopa (AbbVie’s Vyalev), the FDA has issued similar warnings for these drugs, considering the potential risks based on “biological plausibility” and the drugs’ clinical trial data.
Vyalev is the most recently approved carbidopa/levodopa drug, winning FDA approval in 2024. The drug is the successor to AbbVie’s breakthrough 2015 Duopa, which sparked a trend of delivery system innovation in the Parkinson’s disease space as manufacturers seek to avoid the short half-lives associated with oral drugs.
The FDA’s safety testing of carbidopa and levodopa drugs could lend credence to Supernus Pharmaceuticals’ new approach to Parkinson’s disease with Onapgo, a wearable pump that delivers a continuous subcutaneous infusion of the dopamine agonist apomorphine (Apoquin). After receiving approval in 2025 after three FDA rejections, the drug became such a hot topic in the disease field that the company was forced to suspend supply to new patients in November based on “higher-than-expected demand,” Supernas said.
Onapgo shipments have since resumed, and the drug raked in $17.3 million in sales in 2025, while AbbVie’s Vyalev brought in $482 million and its predecessor Duopa brought in $381 million.
