Concerns about the safety of a new class of drugs that prolong the beneficial effects of levodopa in the treatment of Parkinson's disease (PD) have been allayed.
Neurologists were told by speakers at a recent meeting that they could prescribe the COMT (catechol-O-methyl transferase) inhibitor entacapone (Comtess, Orion Pharma) without the need for monitoring liver enzymes.
The safety of COMT-inhibitors has been heavily scrutinised since marketing authorisation for tolcapone was withdrawn in the European Union in November, 1998, following reports of drug-related liver toxicity. Speakers at an Orion symposium held during the European Federation of Neurological Societies' meeting in Lisbon reported that there had been no evidence of liver toxicity in more than 20,000 patients treated with entacapone since it was first licensed in October, 1998. Nor had there been any withdrawals due to liver toxicity in more than 1,000 patients receiving entacapone for six months or more during phase III clinical trials.
It was suggested that structural differences between entacapone and tolcapone might account for the difference in their adverse event profiles, supporting the view that liver toxicity is not a class effect with COMT-inhibitors.
In the clinical trials, the frequency of abnormal liver function tests in patients treated with entacapone was equal to that with placebo (0.3-0.5 per cent). There were no reported cases of hepatitis or jaundice.
Speaking at the symposium, Professor David Brooks (professor of neurology, Imperial College School of Medicine, London) commented: "This is very reassuring news. Our experience with entacapone has far exceeded the point at which the toxicity problems with tolcapone first became apparent."
He added: "Liver enzyme monitoring is a nightmare in clinical practice, and we are very thankful that it is not necessary with entacapone."
Entacapone is currently licensed for use when the effects of levodopa begin to wear off.