Carbidopa / Entacapone / Levodopa

Trade names

• STALEVO

Actions

• Carbidopa inhibits DOPA decarboxylase, preventing conversion of levodopa to dopamine in peripheral tissues.
• Entacapone is a selective and reversible inhibitor of the enzyme catechol-O-methyltransferase (COMT).
• Levodopa (L-DOPA) is the precursor to the neurotransmitters dopamine, norepinephrine and epinephrine.

Route of Administration

Oral

Bioavailability

Carbidopa: 40-70%

Entacapone: 35%

Levodopa: 30%

Plasma protein binding

Carbidopa: 40-70%

Entacapone: 98%

Levodopa: 10-30%

Half-life

Carbidopa: 2 hours

Entacapone: 0.4–0.7 hours

Levodopa: 0.75–1.5 hours

Metabolism

Carbidopa: Not significantly metabolized

Entacapone: Hepatic

Levodopa: Decarboxylation in peripheral tissues and CNS

Elimination

Carbidopa: Renal

Entacapone: Biliary 90%, renal 10%

Levodopa: ~30% of the dose is excreted in urine unchanged

Important side-effects

Hypotension

Arrhythmias

Nausea, vomiting

Disorientation, confusion, delirium, hallucinations, delusions, psychosis

Dyskinesias

Excessive libido

Vivid dreams or insomnia

Somnolence

Recommended dose

Patients already on entacapone can be treated with the combination at the same L-dopa dosage used previously.

Patients not already on entacapone can start treatment at a dose corresponding to their previous L-dopa dose reduced by 10-30%.

Renal impairment

Caution is advised in treating patients with severe renal function impairment with entacapone.

Hepatic impairment

Dose adjustment might be necessary in patients with moderate hepatic function impairment.

Entacapone should not be administered in patients with severe hepatic function impairment.