Including Comtan (entacapone) and Stalevo (entacapone, carbidopa, and levodopa)
ISSUE: An FDA safety review has found no clear evidence of an increased risk of heart attacks, stroke, or other cardiovascular events associated with the use of entacapone for the treatment of Parkinson’s disease. As a result, recommendations for using Comtan (entacapone) and Stalevo (a combination of entacapone, carbidopa, and levodopa) will remain the same in the drug labels.
FDA alerted patients and health care professionals about a possible increased risk for cardiovascular events and death with Stalevo in August 2010. This possible safety issue was observed in a clinical trial called the Stalevo Reduction in Dyskinesia Evaluation in Parkinson’s Disease (STRIDE-PD) and in a meta-analysis that combined the cardiovascular-related findings from 15 clinical trials comparing Stalevo to carbidopa/levodopa. Carbidopa and levodopa have been used extensively and have not been shown to have an increased cardiovascular risk. FDA was concerned that the entacapone in Stalevo was responsible for these cardiovascular risks because the comparison drugs do not contain this ingredient.
To better understand the significance of these findings, FDA required the Stalevo manufacturer, Novartis, to study the potential for cardiovascular risk with the entacapone component of the drug. FDA examined the results from this required study and from one additional study and concluded they do not show an increased risk of cardiovascular adverse events with entacapone. The results observed in the original meta-analysis were driven by results of a single study (STRIDE-PD), which was not designed to assess cardiovascular risks. FDA believes that the meta-analysis and STRIDE-PD results are chance findings and do not represent a true increase in risk due to entacapone.
BACKGROUND: Entacapone-containing products, Comtan and Stalevo, have been shown to be effective in treating symptoms of Parkinson’s disease, such as muscle stiffness, tremors, spasms, and poor muscle control. The combination of entacapone with carbidopa and levodopa in Stalevo has been shown to reduce end-of-dose “wearing-off” in patients with Parkinson’s disease to a greater degree than with entacapone alone or with the two-drug combination of carbidopa and levodopa.
RECOMMENDATION: Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
- Complete and submit the report Online: www.fda.gov/MedWatch/report
- Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178
[10/26/2015 - Drug Safety Communication - FDA]