Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Comtan (Novartis)
200 mg tablets
Approved indication: Parkinson's disease
Australian Medicines Handbook Section 16.2
Inhibitors of catechol-O-methyl transferase (COMT) reduce the metabolism of levodopa. This prolongs the clinical response to levodopa and may benefit patients with Parkinson's disease who experience symptoms as the levodopa wears off. The first of the COMT inhibitors was tolcapone (see `New drugs' Aust Prescr1998;21:54) but it was withdrawn after some patients developed severe hepatic reactions.
Entacapone is taken with each dose of the patient's usual levodopa/dopa decarboxylase inhibitor. The dose of the patient's usual treatment should be reduced when entacapone is started. Patients taking levodopa/benserazide may need a greater reduction as entacapone increases the bioavailability of the combination. Entacapone has a bioavailability of 35% with extensive first-pass metabolism. Most of the drug is excreted as metabolites in the urine.
One study randomised 205 patients, treated with levodopa, to take entacaponeor a placebo for 24 weeks. The amount of time patients had reduced symptoms(`on' time) was increased by 5% in those taking entacapone.1
Most of the adverse effects of entacapone are as a result of increased dopaminergic activity. For example, dyskinesia occurs in 25% of patients. During clinical trials gastrointestinal symptoms were another common reason for patients stopping treatment with entacapone. Patients may develop diarrhoea, abdominal pain, nausea and vomiting. The haemoglobin falls significantly in approximately 2% of patients. Entacapone can affect liver enzymes and there is not yet enough experience with the drug to be certain that it does not share tolcapone's problems.
Although entacapone is efficacious, its usefulness in practice will need further evaluation. Does add-on medication provide a greater benefit than simply increasing the dose of levodopa?
