Tags

Type your tag names separated by a space and hit enter

Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe hepatitis.
Prescrire Int. 2006 Apr; 15(82):54-7.PI

Abstract

(1) When patients with Parkinson's disease who are taking levodopa develop motor fluctuations that do not respond to dose adjustments, the standard treatment is the addition of bromocriptine, a dopaminergic agonist. Evaluation of entacapone fails to show whether the risk-benefit balance of this catechol-O-methyltransferase (COMT) inhibitor is at least as favourable as that of bromocriptine. (2) Tolcapone, another COMT inhibitor, is back on the French market after being withdrawn because of serious hepatic effects. The summary of product characteristics (SPC) specifies that tolcapone must only be used when entacapone treatment fails or is poorly tolerated. (3) Renewal of marketing authorisation was based on one clinical trial in which about half the patients were probably not resistant to entacapone. No difference in efficacy was found between tolcapone and entacapone. There is no firm evidence that tolcapone is effective in a significant number of patients in whom entacapone fails. (4) Placebo-controlled trials show that first-line treatment with tolcapone 100 mg to 200 mg 3 times a day reduces the duration of motor freezing ("off") periods, but the global impact of tolcapone on parkinsonism appears to be limited. (5) Unblinded randomised controlled trials have failed to show that tolcapone is more effective than bromocriptine or pergolide. There are no trials assessing the use of tolcapone in combination with dopamine agonists. (6) Adverse effects were frequent during clinical trials. They were mainly neurological and gastrointestinal, and differed from those associated with bromocriptine. In 1988, shortly after worldwide marketing of tolcapone, 3 cases of fatal fulminant hepatitis were reported among about 60 000 patients who had taken this drug. Some countries, including European Union member states, withdrew marketing authorisation. Other countries, including the United States, left tolcapone on the market but required stringent monitoring of liver function. Due to a lack of transparency on the part of both the manufacturer and the health authorities, we do not know if these measures reduced the risk of severe hepatitis. In the trial versus entacapone, one of the 75 patients treated with tolcapone 300 mg/day had an abnormal increase in serum transaminase activity. (7) In practice, tolcapone has a negative risk-benefit balance.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16604736

Citation

"Tolcapone: New Drug. in Parkinson's Disease: Unacceptable Risk of Severe Hepatitis." Prescrire International, vol. 15, no. 82, 2006, pp. 54-7.
Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe hepatitis. Prescrire Int. 2006;15(82):54-7.
(2006). Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe hepatitis. Prescrire International, 15(82), 54-7.
Tolcapone: New Drug. in Parkinson's Disease: Unacceptable Risk of Severe Hepatitis. Prescrire Int. 2006;15(82):54-7. PubMed PMID: 16604736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe hepatitis. PY - 2006/4/12/pubmed PY - 2006/4/28/medline PY - 2006/4/12/entrez SP - 54 EP - 7 JF - Prescrire international JO - Prescrire Int VL - 15 IS - 82 N2 - (1) When patients with Parkinson's disease who are taking levodopa develop motor fluctuations that do not respond to dose adjustments, the standard treatment is the addition of bromocriptine, a dopaminergic agonist. Evaluation of entacapone fails to show whether the risk-benefit balance of this catechol-O-methyltransferase (COMT) inhibitor is at least as favourable as that of bromocriptine. (2) Tolcapone, another COMT inhibitor, is back on the French market after being withdrawn because of serious hepatic effects. The summary of product characteristics (SPC) specifies that tolcapone must only be used when entacapone treatment fails or is poorly tolerated. (3) Renewal of marketing authorisation was based on one clinical trial in which about half the patients were probably not resistant to entacapone. No difference in efficacy was found between tolcapone and entacapone. There is no firm evidence that tolcapone is effective in a significant number of patients in whom entacapone fails. (4) Placebo-controlled trials show that first-line treatment with tolcapone 100 mg to 200 mg 3 times a day reduces the duration of motor freezing ("off") periods, but the global impact of tolcapone on parkinsonism appears to be limited. (5) Unblinded randomised controlled trials have failed to show that tolcapone is more effective than bromocriptine or pergolide. There are no trials assessing the use of tolcapone in combination with dopamine agonists. (6) Adverse effects were frequent during clinical trials. They were mainly neurological and gastrointestinal, and differed from those associated with bromocriptine. In 1988, shortly after worldwide marketing of tolcapone, 3 cases of fatal fulminant hepatitis were reported among about 60 000 patients who had taken this drug. Some countries, including European Union member states, withdrew marketing authorisation. Other countries, including the United States, left tolcapone on the market but required stringent monitoring of liver function. Due to a lack of transparency on the part of both the manufacturer and the health authorities, we do not know if these measures reduced the risk of severe hepatitis. In the trial versus entacapone, one of the 75 patients treated with tolcapone 300 mg/day had an abnormal increase in serum transaminase activity. (7) In practice, tolcapone has a negative risk-benefit balance. SN - 1167-7422 UR - https://www.unboundmedicine.com/medline/citation/16604736/Tolcapone:_new_drug__In_Parkinson's_disease:_unacceptable_risk_of_severe_hepatitis_ L2 - http://www.diseaseinfosearch.org/result/3332 DB - PRIME DP - Unbound Medicine ER -