Section 03 · Monograph

Carbidopa-levodopa-entacapone

Reviewed Nov 2026FDA label

StalevoDopamine precursor + COMT inhibitor

Indications

Treatment of Parkinson's disease, either (1) as substitution therapy for patients stabilized on the individual components at equivalent doses, or (2) to replace carbidopa-levodopa monotherapy in patients experiencing end-of-dose 'wearing-off' who are taking a total levodopa dose ≤600 mg/day and are not experiencing dyskinesiaFDA-labeled

Levodopa is a dopamine precursor that crosses the blood-brain barrier and is converted to dopamine, replenishing depleted striatal dopamine in Parkinson's disease
Carbidopa is a peripheral aromatic-L-amino-acid decarboxylase inhibitor that reduces peripheral conversion of levodopa to dopamine, increasing levodopa availability to the CNS and reducing peripheral adverse effects
Entacapone is a selective, reversible catechol-O-methyltransferase (COMT) inhibitor that blocks peripheral metabolism of levodopa to 3-O-methyldopa, prolonging levodopa's plasma half-life and extending its clinical effect ('wearing-off' reduction)
Pharmacokinetics: levodopa half-life ~1.7 hours, carbidopa ~1.6–2 hours, entacapone ~0.8–1 hour; entacapone is ~98% protein bound and eliminated mainly via fecal (biliary) excretion

Available as six fixed-ratio tablet strengths (carbidopa/levodopa/entacapone): 12.5/50/200 mg (Stalevo 50), 18.75/75/200 mg (Stalevo 75), 25/100/200 mg (Stalevo 100), 31.25/125/200 mg (Stalevo 125), 37.5/150/200 mg (Stalevo 150), 50/200/200 mg (Stalevo 200)
Select the strength that matches the patient's current levodopa dose per administration; one tablet taken per dosing interval, not split or crushed
Maximum recommended: 8 tablets/day for Stalevo 50–150; 6 tablets/day for Stalevo 200 (clinical experience limited above 1,600 mg entacapone/day)
Titrate dosing interval/strength based on individual response; carbidopa doses below ~70–100 mg/day may be associated with increased nausea/vomiting
Obtain vitamin B6 level before starting; supplement if deficient (may continue therapy while supplementing)
Do not discontinue abruptly — taper to reduce risk of withdrawal-emergent hyperpyrexia and confusion

Nonselective MAO inhibitors: contraindicated — hypertensive risk
Catecholamine-metabolized drugs (isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, alpha-methyldopa, apomorphine, isoetherine, bitolterol): risk of increased heart rate, arrhythmia, or exaggerated blood pressure response — use with caution
Antihypertensives: increased risk of symptomatic postural hypotension
Tricyclic antidepressants: rare reports of hypertension and dyskinesia
Dopamine D2-receptor antagonists (metoclopramide, phenothiazines, butyrophenones, risperidone): may reduce levodopa effectiveness
Isoniazid, phenytoin, papaverine: may reduce levodopa efficacy
Iron salts/iron-containing multivitamins: reduce bioavailability via chelation
Drugs affecting biliary excretion/glucuronidation (probenecid, cholestyramine, erythromycin, rifampicin, ampicillin, chloramphenicol): may interfere with entacapone excretion
Warfarin: entacapone increases R-warfarin AUC (~18%) and INR (~13%); monitor INR closely when starting or stopping Stalevo

Dyskinesia/hyperkinesia (dyskinesia ~25% vs 15% placebo) — often occurs earlier and at lower doses than with carbidopa-levodopa alone
Gastrointestinal: diarrhea (~10% vs 4%), nausea (~14% vs 8%), abdominal pain, vomiting, dry mouth
Urine discoloration (brownish/reddish), occurs in about 10% of patients — harmless
Diarrhea/colitis, including postmarketing reports of microscopic colitis; onset typically 4–12 weeks but can occur earlier or later; may require discontinuation
Rhabdomyolysis reported (myalgia, elevated CPK/myoglobin, fever, altered consciousness)
Postmarketing hepatotoxicity with cholestatic features
Hallucinations/psychotic-like behavior

Vitamin B6 levels at baseline and periodically; supplement if deficient
INR when initiating in patients on warfarin
Periodic hepatic function testing during extended therapy
Direct questioning for daytime somnolence and sudden sleep episodes, especially before driving
Screen for impulse control/compulsive behaviors (gambling, hypersexuality, spending, eating)
Monitor for diarrhea; evaluate for colitis if severe/persistent
Watch for signs of withdrawal-emergent hyperpyrexia and confusion during dose reduction or discontinuation
Assess for depression/suicidality and psychosis

No adequate human pregnancy data; animal studies showed carbidopa-levodopa-related visceral/skeletal malformations in rabbits and decreased live pups in rats; entacapone produced fetal variations, resorptions, and eye anomalies in animal studies at high exposures
Levodopa is present in human milk and may decrease prolactin secretion, potentially inhibiting lactation; no human data on entacapone in milk (present in rat milk at 2–3x plasma levels)
Weigh breastfeeding benefits against maternal need for therapy and potential infant risk