Carbidopa/Levodopa

In its safety review, the FDA found 14 causes of seizures linked to vitamin B6 deficiency in patients taking the common Parkinson’s disease drugs. 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. 

iStock, undefined undefined The FDA detected 14 cases of vitamin B6 deficiency–linked seizures and two deaths in patients with Parkinson’s disease taking carbidopa/levodopa drugs. Both AbbVie and Novartis market levodopa-based products. Products containing levodopa and carbidopa, a common drug combination for treating Parkinson’s disease, could trigger seizures, the FDA has found. The agency conducted a safety review of drugs carrying these compounds and found 14 cases of seizures linked to vitamin B6 deficiency, according to a safety alert on Friday. In all of these cases, levodopa doses exceeded 1,000 mg per day. Seizures were typically focal-onset, meaning they started in a limited region of the brain. They then spread to include both hemispheres, leading to convulsions and causing emergencies in some cases. Two patients died, both of whom had had low vitamin B6 levels and poorly controlled seizures, the FDA said. Nine patients were given vitamin B6 supplementation, which in all cases led to the resolution of their seizures. All 14 cases of carbidopa/levodopa-linked seizures were detected through post-marketing surveillance or found in the medical literature, “so there are likely additional cases about which we are unaware,” the FDA said. While the safety signals arose in those taking oral formulations and enteral suspensions of carbidopa/levodopa, the regulator did not dismiss the possibility that other products—such as injectables or those that use additional compounds to enhance the original drug combo—could carry the same risk. “Biological plausibility suggests there may be a similar risk across all drug products containing carbidopa/levodopa,” the FDA wrote. The agency has already notified all manufacturers of drugs carrying carbidopa/levodopa, asking them to update the labels of their respective products to carry warnings for vitamin B6 deficiency-associated seizures. In the meantime, healthcare professionals should assess their patients’ vitamin B6 levels at baseline and throughout treatment, and consider supplementation as needed, the FDA recommended. Levodopa is a synthetic drug that, once it reaches the brain, is converted into dopamine, a neurotransmitter that is deficient in patients with Parkinson’s disease. Levodopa’s therapeutic benefits for Parkinson’s were first established in the 1960s, and the first drug that combined it with the decarboxylase inhibitor carbidopa—which improved its efficacy and safety—entered the market in 1975 . The combo remains in use today. In October 2024, the FDA approved AbbVie’s Vyalev , a levodopa-based therapy for advanced Parkinson’s disease. The product contains foscarbidopa and foslevodopa, prodrugs that can be given continuously over 24 hours as a subcutaneous infusion. Novartis also owns a carbidopa/levodopa product in Stalevo , which additionally uses entacapone to sustain heightened levels of the drug in the bloodstream. The industry is now opening up new therapeutic avenues for Parkinson’s disease, however. Eli Lilly in January scooped up Ventyx Biosciences for $1.2 billion, gaining access to a pipeline of drugs that target the NLRP3 inflammatory cascade, an underlying pathway driving the condition. Also looking at an immune-centered approach to Parkinson’s is AC Immune, which in December 2025 demonstrated slower disease progression in patients treated with its anti-alpha-synuclein therapy. Parkinson’s disease 5 Investigational Therapies That Could Change the Parkinson’s Landscape From opening new therapeutic mechanisms to repairing neuronal damage, investigational molecules from Ventyx Therapeutics, AC Immune, Gain Therapeutics and more could shape the future of Parkinson’s disease treatment. January 26, 2026 · 9 min read · Tristan Manalac Read more