4.9.1.4 Dopamine enzyme inhibitors / catechol-O-methyltransferase inhibitors (COMT inhibitors)

ChoiceDrugDosage
1st choiceEntacapone tablets 200mgDose:
200mg with each dose of levodopa with dopa-decarboxylase inhibitor; max 2g daily
2nd choiceTolcapone 100mg tabletsDose: 100mg three times daily, leave 6 hours between each dose; max 200mg three times daily in exceptional circumstances; first daily dose should be taken at the same time as levodopa with dopa-decarboxylase inhibitor

Prescribing Notes

  • COMT inhibitors are not recommended as first line agents for PD.
  • There is no evidence to support their use as neuroprotective therapies.
  • Entacapone or tolcapone may be used for management of motor fluctuations.
  • A triple combination preparation of levodopa, caridopa and entacapone (Stalevo® or Sastravi®) may be suitable for patients requiring entacapone who are having problems with concordance. Sastravi® is currently the ‘branded generic’ combination preparation with the lowest acquisition cost.
  • Due to the risk of hepatotoxicity, tolcapone should be prescribed under specialist supervision only, when other COMT inhibitors combined with co-beneldopa or co-careldopa are ineffective or not tolerated. LFT monitoring is required (see shared care guideline).
  • Tolcapone should only be continued beyond three weeks if there is substantial improvement in symptom control.