"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"...
Management of acute overdo sage with Stalevo® (carbidopa, levodopa and entacapone) is the same as management of acute overdosage with levodopa and entacapone. Pyridoxine is not effective in reversing the actions of Stalevo (carbidopa, levodopa and entacapone) ® .
Hospitalization is advised, and general supportive measures should be employed, along with immediate gastric lavage and repeated doses of charcoal over time. This may hasten the elimination of entacapone in particular, by decreasing its absorption/reabsorption from the GI tract. Intravenous fluids should be administered judiciously and an adequate airway maintained.
The adequacy of the respiratory, circulatory and renal systems should be carefully monitored and appropriate supportive measures employed. Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs, increasing the risk of drug interactions (especially catechol-structured drugs) should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdosage is not known. Hemodialysis or hemoperfusion is unlikely to reduce entacapone levels due to its high binding to plasma proteins.
There are very few cases of overdosage with levodopa reported in the published literature. Based on the limited available information, the acute symptoms of levodopa/dopa decarboxylase inhibitor overdosage can be expected to arise from dopaminergic overstimulation. Doses of a few grams may result in CNS disturbances, with an increasing likelihood of cardiovascular disturbance (e.g., hypotension, tachycardia) and more severe psychiatric problems at higher doses. An isolated report of rhabdomyolysis and another of transient renal insufficiency suggest that levodopa overdosage may give rise to systemic complications, secondary to dopaminergic overstimulation.
There have been no reported cases of either accidental or intentional overdose with entacapone tablets. However, COMT inhibition by entacapone treatment is dose-dependent. A massive overdose of entacapone may theoretically produce a 100% inhibition of the COMT enzyme in people, thereby preventing the O-methylation of endogenous and exogenous catechols.
The highest single dose of entacapone administered to humans was 800 mg, resulting in a plasma concentration of 14.1 µg/mL. The highest daily dose given to humans was 2400 mg, administered in one study as 400 mg six times daily with carbidopa-levopoda for 14 days in 15 Parkinson's disease patients, and in another study as 800 mg t.i.d. for 7 days in 8 healthy volunteers. At this daily dose, the peak plasma concentrations of entacapone averaged 2.0 µg/mL (at 45 min., compared to 1.0 and 1.2 µg/mL with 200 mg entacapone at 45 min.). Abdominal pain and loose stools were the most commonly observed adverse events during this study. Daily doses as high as 2000 mg entacapone have been administered as 200 mg 10 times daily with carbidopa-levodopa or benserazide-levodopa 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 1600 mg is limited.
The range of lethal plasma concentrations of entacapone based on animal data was 80-130 µg/mL in mice. Respiratory difficulties, ataxia, hypoactivity, and convulsions were observed in mice after high oral (gavage) doses.
Stalevo® (carbidopa, levodopa and entacapone) tablets are contraindicated in patients who have demonstrated hypersensitivity to any component (carbidopa, levodopa, or entacapone) of the drug or its excipients.
Monoamine oxidase (MAO) and COMT are the two major enzyme systems involved in the metabolism of catecholamines. It is theoretically possible, therefore, that the combination of entacapone and a non-selective MAO inhibitor (e.g., phenelzine and tranylcypromine) would result in inhibition of the majority of the pathways responsible for normal catecholamine metabolism. As with carbidopa-levodopa, nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with Stalevo (carbidopa, levodopa and entacapone) ® . These inhibitors must be discontinued at least two weeks prior to initiating therapy with Stalevo (carbidopa, levodopa and entacapone) ® . Stalevo (carbidopa, levodopa and entacapone) ® may be administered concomitantly with the manufacturer's recommended dose of MAO inhibitors with selectivity for MAO type B (e.g., selegiline HC1). (See PRECAUTIONS: DRUG INTERACTIONS.)
Stalevo (carbidopa, levodopa and entacapone) ® is contraindicated in patients with narrow-angle glaucoma.
Because levodopa may activate malignant melanoma, Stalevo (carbidopa, levodopa and entacapone) ® should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.
Last reviewed on RxList: 11/8/2010
This monograph has been modified to include the generic and brand name in many instances.
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