"Using data from over 18,000 patients, scientists have identified more than two dozen genetic risk factors involved in Parkinson's disease, including six that had not been previously reported. The study, published in Nature Genetics, was partially"...
The post-marketing data include several cases of overdose. The highest reported dose of entacapone was at least 40,000 mg. The acute symptoms and signs commonly seen in these cases included somnolence and decreased activity, states related to depressed level of consciousness (e.g., coma, confusion and disorientation) and discolorations of skin, tongue and urine, as well as restlessness, agitation and aggression.
COMT inhibition by entacapone treatment is dose-dependent. A massive overdose of Comtan (entacapone) may theoretically produce a 100% inhibition of the COMT enzyme in humans, thereby preventing the metabolism of endogenous and exogenous catechols.
The highest daily dose given to humans was 2,400 mg, administered in one study as 400 mg six times daily with levodopa and carbidopa for 14 days in 15 Parkinson's disease patients, and in another study as 800 mg three times daily for 7 days in 8 healthy volunteers. At this daily dose, the peak plasma concentrations of entacapone averaged 2.0 mcg per mL (at 45 minutes, compared to 1.0 mcg per mL and 1.2 mcg per mL with 200 mg entacapone at 45 minutes). Abdominal pain and loose stools were the most commonly observed adverse events during this study. Daily doses as high as 2,000 mg Comtan have been administered as 200 mg 10 times daily with levodopa and carbidopa or levodopa and benserazide for at least 1 year in 10 patients, for at least 2 years in 8 patients and for at least 3 years in 7 patients. Overall, however, clinical experience with daily doses above 1,600 mg is limited.
The range of lethal plasma concentrations of entacapone based on animal data was 80 mcg per mL to 130 mcg per mL in mice. Respiratory difficulties, ataxia, hypoactivity, and convulsions were observed in mice after high oral (gavage) doses.
Management Of Overdose
Management of Comtan overdose is symptomatic; there is no known antidote to Comtan. Hospitalization is advised, and general supportive care is indicated. There is no experience with hemodialysis or hemoperfusion, but these procedures are unlikely to be of benefit, because Comtan is highly bound to plasma proteins. An immediate gastric lavage and repeated doses of charcoal over time may hasten the elimination of Comtan by decreasing its absorption and reabsorption from the gastrointestinal (GI) tract. The adequacy of the respiratory and circulatory systems should be carefully monitored and appropriate supportive measures employed. The possibility of drug interactions, especially with catechol-structured drugs, should be borne in mind.
Comtan is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.
Last reviewed on RxList: 6/27/2014
This monograph has been modified to include the generic and brand name in many instances.
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