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Parkinson's disease - Management
How are catechol-O-methyl transferase inhibitors used in seconday care?

Catechol-O-methyl transferase inhibitors (COMT) inhibitors (entacapone and tolcapone)

  • Work by further inhibiting the peripheral metabolism of levodopa, thereby increasing its bioavailability to the brain and prolonging the action of dopamine. Tolcapone also inhibits central COMT metabolism.
  • When used as an adjuvant to levodopa:
    • COMT inhibitors reduce off-time and levodopa dose, and improve motor impairments.
    • This is at the expense of increased dopaminergic adverse events such as nausea, vomiting, and dyskinesia.
  • Entacapone and tolcapone have different methods of administration:
    • Entacapone must be given with each dose of levodopa/dopa-decarboxylase inhibitor (that is, each dose of co-beneldopa or co-careldopa), which may be up to ten times a day.
    • Tolcapone is given three times a day (and does not have to be taken at the same time as a levodopa dose).
  • In view of problems with concordance, the National Institute for Health and Clinical Excellence (NICE) recommends that people requiring entacapone should be offered the triple-combination preparation of levodopa, carbidopa, and entacapone (Stalevo®).
  • Tolcapone was suspended by the Committee on Safety of Medicines in November 1998 because of unpredictable serious hepatic reactions. However, in April 2004 the suspension was lifted due, in part, to evidence of increased efficacy for tolcapone over entacapone in the control of motor fluctuations in advanced Parkinson's disease.
    • Tolcapone is now indicated for people who fail to respond to, or are intolerant of, other COMT inhibitors, but may only be prescribed by specialists in managing Parkinson's disease.
    • Drug monitoring is required for people taking tolcapone.

[CSM, 2004; National Collaborating Centre for Chronic Conditions, 2006]

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