Tolcapone

How it works

By inhibiting COMT both peripherally and centrally, it slows the breakdown of levodopa and dopamine, prolonging and smoothing the dopaminergic effect of each levodopa dose.

Prescribing in practice

• It can cause potentially fatal hepatotoxicity, so it is reserved for patients not adequately controlled on or intolerant of other COMT inhibitors, and liver function must be monitored regularly with treatment stopped if enzymes rise significantly.
• Enhancing dopaminergic activity may worsen dyskinesia, nausea and hallucinations, often requiring the levodopa dose to be reduced.
• It can colour the urine and has rarely been linked with a neuroleptic malignant-like syndrome on abrupt withdrawal.

Monitoring

Monitor liver transaminases regularly throughout treatment, together with blood pressure, dyskinesia and neuropsychiatric symptoms.

Counselling the patient

• Attend for the scheduled liver blood tests and report nausea, fatigue, dark urine or yellowing of the skin urgently.
• Tell your clinician if involuntary movements, confusion or hallucinations increase.

Evidence & guidelines

Its restricted, hepatically monitored use reflects MHRA and regulatory warnings on serious hepatotoxicity.