entacapone
Brand: Comtan, Stalevo (with levodopa/carbidopa)
Prototype Drug
Drug Class: COMT inhibitor
Drug Family: antiparkinsonian
Subclass: catechol-O-methyltransferase (COMT) inhibitor
Organ Systems: cns
Mechanism of Action
Peripherally-acting COMT inhibitor; blocks the enzyme responsible for methylating levodopa to 3-O-methyldopa (an inactive metabolite that competes with levodopa for transport across the BBB). By inhibiting peripheral COMT, entacapone increases the bioavailability of levodopa that reaches the brain by approximately 30-50%, extending and enhancing its effect.
COMT (catechol-O-methyltransferase)
Indications
- Parkinson's disease with end-of-dose motor fluctuations (wearing off) as adjunct to levodopa/carbidopa
Contraindications
- concurrent non-selective MAOIs
- pheochromocytoma
Adverse Effects
Common
- dyskinesia (from enhanced levodopa effect)
- nausea
- diarrhea
- urine discoloration (orange-brown; harmless)
- abdominal pain
Serious
- severe diarrhea requiring hospitalization
- rhabdomyolysis (rare)
- neuroleptic malignant syndrome-like syndrome if abruptly stopped with levodopa
Pharmacokinetics (ADME)
| Absorption | well absorbed; bioavailability ~35%; food has no significant effect |
| Distribution | protein binding ~98%; Vd ~20 L |
| Metabolism | hepatic glucuronidation; peripheral COMT inhibition only (does not cross BBB at therapeutic doses) |
| Excretion | primarily fecal (90%) |
| Half-life | 0.4-0.7 hours (but COMT inhibition lasts several hours) |
| Onset | within the first levodopa dose |
| Peak | 1 hour |
| Duration | administered with each levodopa dose |
| Protein Binding | 98% |
| Vd | 20 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| non-selective MAOIs | blockade of both MAO and COMT pathways causes major catecholamine accumulation; hypertensive crisis | contraindicated |
| drugs metabolized by COMT (epinephrine, dobutamine, methyldopa) | increased catecholamine exposure | moderate |
Nursing Considerations
- Entacapone must be administered with each dose of levodopa/carbidopa — it has no effect when taken alone.
- Warn patients that urine may turn orange-brown or brownish-yellow; this is harmless pigmentation from entacapone metabolites and not hematuria.
- When starting entacapone, levodopa dose may need to be decreased by 10-30% to prevent increased dyskinesia from enhanced levodopa bioavailability.
- Diarrhea is dose-limiting in up to 10% of patients and may cause significant dehydration; monitor fluid status and report severe diarrhea.
Clinical Pearls
- Entacapone extends the clinical effect of each levodopa dose by 30-50 minutes, a clinically meaningful benefit in patients experiencing 'wearing off' (end-of-dose deterioration) in advanced Parkinson's disease.
- Stalevo (levodopa/carbidopa/entacapone) combines all three agents in one tablet to simplify the dosing regimen, though it cannot be used for flexible levodopa dose adjustments without changing all three components simultaneously.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.