EMEA. Following the withdrawal of the catechol-O-methyl transferase (COMT) inhibitor, tolcapone, in November 1998 due to hepatotoxicity, the Committee for Proprietary Medicinal Products (CPMP) has reviewed the safety data of a related product, entacapone (Comtess/Comtan: Orion), indicated for the adjunctive treatment of Parkinson’s disease.

The most recent safety data indicate that entacapone does not appear to be hepatotoxic. However rare reports of clinically significant increases in liver enzymes have been reported. The CPMP has been made aware that abrupt withdrawal of a COMT inhibitor or dopaminergic medication has resulted in neuroleptic malignant syndrome (NMS) in a small number of cases. Rhabdomyolysis (severe disease of the skeletal muscle) secondary to severe dyskinesia and NMS have also been observed in rare cases in patients with Parkinson’s disease.

Although treatment with entacapone or its discontinuation have not been associated with either NMS or rhabdomyolysis, the marketing authorization holders considered it appropriate to introduce provisional changes in the prescribing and patient information.

The following information will be added to the patient information:

Comtess/Comtan must not be used if you have a history of Neuroleptic Malignant Syndrome and/or non-traumatic rhabdomyolis (a rare form of muscle disorder).

If you need to stop taking Comtess/Comtan, please consult your doctor. Withdrawal of Comtess/Comtan treatment may have to be done gradually and other antiparkinsonian therapy may need to be adjusted to prevent worsening of parkinsonian symptoms or unwanted side effects (e.g. rigidity, shakiness, agitation, confusion, fever).

Reference: EMEA Press Release: Entacapone (Comtess/Comtan): update of product information, London 23 November 1998.