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The review is an update to a drug safety communication initially issued in 2010 after trial results suggested a possible increased risk for prostate cancer with use of entacapone.
The FDA has issued an updated safety announcement regarding the risk of prostate cancer with use of Parkinson disease drug entacapone. Following a review of additional data, the agency found no increased risk for prostate cancer and will not require any changes to the prescribing information for Comtan (entacapone) or Stalevo (entacapone, carbidopa, levodopa).1
Comtan, which was approved in 1999, and Stalevo, which was approved in 2003, have both been shown to reduce off time in patients with Parkinson disease treated with carbidopa/levodopa.
The original drug safety communication was released in March 20102 after the agency became aware of a clinical trial3 whose results suggested that there was a possible increased risk for prostate cancer associated with the entacapone component of Stalevo. At the time, the FDA required drug manufacturer Novartis to conduct a study to further evaluate this risk while the agency also conducted its own independent review that utilized data from the Department of Veterans Affairs health system.
The follow-up study conducted by Novartis4 evaluated the incidence of prostate cancer in patients with Parkinson disease who were treated with entacapone plus conventional Parkinson treatment (dopa decarboxylase inhibitor/levodopa) compared to patients treated with conventional Parkinson treatment plus a dopamine agonist or monoamine oxidase B inhibitor.
The study, conducted in Finland, included 11,396 men with Parkinson disease, of whom 1141 were treated with entacapone. Over the course of an average follow-up of 4.6 years, 359 cases of prostate cancer were recorded, leading to 89 prostate cancer-related deaths. Statistical analysis showed no increased risk for prostate cancer or prostate cancer mortality in the treatment group with entacapone (hazard ratio [HR] 1.05; 95% CI, 0.76-1.44; HR 0.93; 95% CI, 0.43-1.98) compared to conventional treatment without entacapone. Among patients who were treated with entacapone more than 360 cumulative days, the hazard ratios for prostate cancer incidence and mortality were 0.82 (95% CI, 0.56-1.18) and 1.27 (95% CI, 0.59-2.72), respectively.
The study conducted by the FDA5 included 17,666 men with Parkinson disease who were treated with carbidopa/levodopa and add-on entacapone (n=5257) to a control cohort who received add-on therapy with a dopamine agonist or monoamine oxidase B inhibitor (n=12,409). Over a mean follow-up of 3.1 and 4.0 years, respectively, 23 cases of prostate cancer occurred in the entacapone group compared with 97 cases in the control cohort. No increased risk was observed in patients treated with entacapone for more than 2 years (adjusted HR 1.08; 95% CI, 0.46-2.51).
Given the results, “we concluded that entacapone use is not associated with an increased risk of prostate cancer,” the FDA wrote.1 The agency encourages health care professionals to follow standard prostate screening recommendations for their patients, and advises patients to continue taking their medication(s) as prescribed.
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1. US Food and Drug Administration. FDA review finds no increased risk of prostate cancer with Parkinson's disease medicines containing entacapone (Comtan, Stalevo). fda.gov/drugs/drug-safety-and-availability/fda-review-finds-no-increased-risk-prostate-cancer-parkinsons-disease-medicines-containing. Updated August 13, 2019. Accessed August 14, 2019.
2. US Food and Drug Administration. FDA Drug Safety Communication: Ongoing Safety Review of Stalevo (entacapone/carbidopa/levodopa) and possible development of Prostate Cancer. fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm206363.htm. Updated April 7, 2010. Accessed August 14, 2019.
3. Stocchi F, Rascol O, Kieburtz K, et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann Neurol.2010;68(1):18-27.
4. Korhonen P, KuoppamÃ¤ki M, Prami T, et al. Entacapone and prostate cancer risk in patients with Parkinson's disease. Mov Disord. 2015;30(5):724-8.
5. Major JM, Dong D, Cunningham F, et al. Entacapone and prostate cancer in Parkinson’s disease patients: A large Veterans Affairs healthcare system study. Parkinsonism and Relat Disord. 2018;53:46-52.