Levodopa with carbidopa and entacapone

How it works

Levodopa is converted to dopamine in the brain to replace deficient striatal dopamine; carbidopa blocks peripheral levodopa breakdown, while entacapone inhibits COMT to prolong levodopa availability and smooth motor response.

Prescribing in practice

• Do not stop abruptly, as sudden withdrawal can precipitate a neuroleptic malignant syndrome-like reaction with rigidity, fever and confusion.
• Entacapone commonly causes harmless reddish-brown discolouration of urine and can worsen dopaminergic dyskinesias and diarrhoea.
• Be alert for impulse control disorders and sudden onset of sleep, and warn patients accordingly.

Monitoring

Monitor motor response, blood pressure including postural drops, and watch for behavioural changes during treatment.

Counselling the patient

• Never stop the medicine suddenly without medical advice.
• Harmless reddish-brown urine discolouration can occur.
• Report new gambling, compulsive behaviours or episodes of falling asleep unexpectedly.

Evidence & guidelines

Combining COMT inhibition with levodopa is an established strategy in Parkinson's disease to extend levodopa effect and reduce end-of-dose wearing-off.