Safety and tolerability of COMT inhibitors.
Combining levodopa with the catechol-O-methyltransferase (COMT) inhibitor entacapone has been shown to be an effective strategy in the management of Parkinson's disease (PD) patients experiencing motor fluctuations. Safety and tolerability information has come from postmarketing surveillance studies as well as several randomized, placebo-controlled trials with long-term open-label extension phases specifically investigating the safety and tolerability of levodopa plus entacapone. Results show the most common dopaminergic side effects to be dyskinesia and nausea, which result from the increased bioavailability of levodopa and can be readily managed. Non-dopaminergic side effects include diarrhea and harmless urine discoloration. There is no convincing evidence of hepatic injury with entacapone use, and therefore monitoring of liver enzymes is unnecessary. With over 300,000 patient-years of exposure, levodopa combined with entacapone can be considered safe and well tolerated.
Brooks
David J
DJ
MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, United Kingdom.
D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use; D001577:Benzophenones / Q000009:adverse effects; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D009325:Nausea / Q000139:chemically induced; D009570:Nitriles; D009596:Nitrophenols; D010300:Parkinson Disease / Q000188:drug therapy*; D012449:Safety; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D009596:Nitrophenols; C071192:entacapone; D000077867:Tolcapone