The Food and Drug Administration has approved new labeling that relaxes the liver enzyme monitoring recommendations for tolcapone, an adjunctive treatment for Parkinson's disease, according to the drug's manufacturer.
The new label recommends monitoring serum glutamic-pyruvic transaminase (SGPT/ALT) and serum glutamic-oxaloacetic transaminase (SGOT/AST) at baseline, then every 2–4 weeks for the first 6 months. After that, periodic monitoring is recommended as the prescribing physician deems clinically relevant.
The drug was approved as Tasmar in January 1998 for adjunctive use in patients whose Parkinson's symptoms are not adequately controlled despite being on adequate doses of levodopa/carbidopa, according to the FDA. By October of that year, FDA had received reports of three cases of fatal fulminant liver failure; the agency said many more cases might have gone unreported. The reports prompted a black box warning on the drug label, citing an increased risk for liver failure of up to 100 times above the background population. The warning recommended liver enzyme monitoring every 2 weeks for the first year of therapy, every 4 weeks for the next 6 months, and then every 8 weeks thereafter. It also required patients to sign a consent form acknowledging that they understood the increased risk of liver failure associated with the drug.
However, based on a data analysis by Valeant Pharmaceuticals International, which makes the drug, FDA has concluded that the risk of liver failure is probably lower than initially estimated. The analysis included more than 40,000 patient years of prescription data and laboratory test data from more than 3,400 patients who participated in tolcapone clinical trials.
“Recent data suggest that hepatic dysfunction associated with Tasmar is rare and can be addressed with less restrictive monitoring,” Dr. C. Warren Olanow, professor and chair of neurology at Mount Sinai School of Medicine, New York, said in a statement on the company's Web site (www.valeant.com
The new label information should show up soon on the drug's packaging, said Dan Springer, a spokesman for Valeant.