entacapone and Nausea

To investigate efficacy and safety of entacapone across phase III studies in Parkinson's disease (PD) with wearing-off symptoms.. Retrospective, pooled analysis of four phase 3 randomized, double-blind, placebo-controlled studies with entacapone.. 475 of 808 patients with PD received entacapone and 333 received placebo. Entacapone improved daily OFF- and ON-times (change from baseline) by 0.8 h compared with placebo (P < 0.0001 for both variables). Entacapone was also better in UPDRS II (P < 0.01) and III (P < 0.01) scores and global evaluation (P < 0.05). Similar benefits were seen in subgroups of patients with and without dopamine agonist (DA) or selegiline, but the subgroup results should be regarded as exploratory. Entacapone was generally well tolerated. Dyskinesia and nausea were more frequently reported by patients on entacapone (25.7% and 14.5% of patients, respectively) than those receiving placebo (15.6% and 6.0%, respectively). However, there was no difference in reports of hallucinations between entacapone (4.8%) and placebo (4.8%).. Entacapone improved daily OFF- and ON-times by a mean of 0.8 h compared with placebo across the four pooled efficacy studies and was generally well tolerated. The results of this pooled analysis potentially serve as a useful benchmarking data for new therapies (especially levodopa products) in advanced patients with PD.

Topics: Aged; Antiparkinson Agents; Catechols; Clinical Trials, Phase III as Topic; Dopamine Agonists; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Middle Aged; Nausea; Nitriles; Parkinson Disease; Randomized Controlled Trials as Topic; Retrospective Studies; Selegiline

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.

Topics: Aged; Antiparkinson Agents; Benzophenones; Catechol O-Methyltransferase Inhibitors; Catechols; Clinical Trials as Topic; Dyskinesia, Drug-Induced; Enzyme Inhibitors; Female; Humans; Liver; Male; Nausea; Nitriles; Nitrophenols; Parkinson Disease; Safety; Tolcapone

A levodopa/carbidopa/entacapone combination product (Stalevo) was recently approved to treat patients with idiopathic Parkinson's disease (PD) who experience end-of-dose "wearing-off." Stalevo is available in dose combinations of levodopa/carbidopa/entacapone 50/12.5/200 mg (Stalevo 50), 100/25/200 mg (Stalevo 100), and 150/37.5/200 mg (Stalevo 150). A series of pharmacokinetic studies demonstrated bioequivalence between Stalevo and corresponding dosages of levodopa/carbidopa plus entacapone. A clinical advantage of Stalevo is that patients can take one pill rather than two (or more) separate tablets. In addition, Stalevo 50 and 100 tablets are smaller than entacapone tablets. These advantages may be particularly beneficial for patients taking many pills, those who have difficulty following complex medication regimens, and those with swallowing difficulty. Most PD patients taking levodopa/carbidopa immediate-release (IR) plus entacapone can be directly switched to the corresponding dose Stalevo product. For fluctuating PD patients taking levodopa/carbidopa IR without entacapone, switching to the corresponding Stalevo tablet is analogous to adding entacapone. In switching patients who are receiving levodopa/carbidopa controlled-release (CR), it should be noted that the bioavailability of levodopa from levodopa/carbidopa CR is approximately 70-75% that of levodopa/carbidopa IR products, including Stalevo.

Topics: Aged; Antiparkinson Agents; Area Under Curve; Biological Availability; Carbidopa; Catechols; Clinical Trials, Phase III as Topic; Drug Combinations; Drug Evaluation; Female; Headache; Humans; Levodopa; Male; Middle Aged; Nausea; Nitriles; Reference Values; Therapeutic Equivalency

Topics: Carbidopa; Catechols; Diarrhea; Dose-Response Relationship, Drug; Drug Combinations; Humans; Levodopa; Nausea; Nitriles; Parkinson Disease