Oral Parkinson's disease and "end of dose" motor fluctuations
Adult: Each tab contains levodopa and carbidopa in a ratio of 4:1 and entacapone 200 mg: 1 tab at each dose. Max: 8 tab daily. Doses are individualised based on therapeutic response; may be adjusted by changing strength or adjusting interval. Patients previously treated w/ carbidopa/levodopa immediate-release tab (1:4 ratio): W/ current entacapone therapy: May switch directly to corresponding strength or slightly higher dose of combination tab. W/o entacapone therapy: May switch directly to corresponding strength or slightly lower dose of levodopa; patients taking levodopa doses >800 mg daily or w/ dyskinesia should start on a separate entacapone therapy before switching to the combination preparation, w/ 10-30% reduction in levodopa dose.
May be taken with or without food. Keep a consistent diet.
Narrow-angle glaucoma, phaeochromocytoma, history of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis. Severe hepatic impairment. Concurrent use of or w/in 14 days of discontinuing non-selective MAOIs.
Patient w/ ischaemic heart disease, severe CV or pulmonary disease, bronchial asthma, endocrine disease, chronic wide-angle glaucoma, biliary obstruction; history of peptic ulcer disease, convulsions, MI w/ residual atrial nodal or ventricular arrhythmias; past or current psychoses. Avoid abrupt withdrawal or dose reduction. Mild to moderate hepatic and severe renal impairment.
Symptoms: Confusional state, agitation, bradycardia, ventricular tachycardia, Cheyne-Stokes respiration, coma; skin, tongue, conjunctiva and urine discolouration. Management: General supportive measures w/ immediate gastric lavage and repeated doses of charcoal. Appropriate anti-arrhythmic therapy may be given as required.
Increased heart rate and/or BP, arrhythmia w/ drugs metabolised by COMT. Risk of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion and thickening w/ ergot derived dopaminergic agents. Risk of symptomatic postural hypotension w/ antihypertensive agents. Dopamine D2 receptor antagonists (e.g. metoclopramide) and isoniazid may reduce the therapeutic effect of levodopa. Phenytoin and papaverine may reverse the effect of levodopa. Formation of chelates w/ Fe salts. Potentially Fatal: Risk of increased adrenergic tone w/ non-selective MAOIs (e.g. phenelzine, tranylcypromine).
Impaired absorption w/ high protein diet. May enhance the sedative effect of alcohol.
False-negative reaction in glucose-oxidase tests for glucosuria. False-positive urine ketones. False diagnosis for phaeochromocytoma based on urine levels of catecholamine.
Description: Levodopa is the metabolic precursor of dopamine. It crosses the blood-brain barrier and is converted to dopamine in the brain. Carbidopa increases the amount of levodopa that is transported into the CNS by inhibiting the decarboxylation of peripheral levodopa. Entacapone is a selective inhibitor of COMT which alters the pharmacokinetics of levodopa, resulting to increased and more sustained levodopa serum levels. Pharmacokinetics: Absorption: Carbidopa: Rapidly but incompletely absorbed from the GI tract. Levodopa: Rapidly absorbed from the GI tract. Time to peak plasma concentration: W/in 2 hr. Entacapone: Bioavailability: Approx 35%. Time to peak plasma concentration: Approx 1 hr. Impaired absorption w/ high protein diet. Distribution: Levodopa: Crosses the blood-brain barrier and placenta; enters breast milk. Plasma protein binding: Approx 98% (entacapone); approx 10-30% (levodopa). Metabolism: Levodopa: Rapidly metabolised to dihydroxyphenylacetic acid and homovanillic acid via decarboxylation by aromatic L-amino acid enzyme; other routes include O-methylation, transamination and oxidation. Entacapone: Undergoes extensive first-pass metabolism. Excretion: Carbidopa: Via urine, as unchanged drug and metabolites. Levodopa: Via urine (approx 80%); faeces (small amounts). Elimination half-life: Approx 30-60 min. Entacapone: Mainly via faeces; urine (approx 10-20%, mainly as glucuronide conjugates).
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