entacapone (en-tak-a-pone) Comtan

 Indications

With levodopa/carbidopa to treat idiopathic Parkinson’s

disease when signs and symptoms of end-of-dose

“wearing-off” (so-called fluctuating patients) occur.

Action

Acts as a selective and reversible inhibitor of the enzyme

catechol O-methyltransferase (COMT). Inhibition

of this enzyme prevents the breakdown of levodopa, increasing

availability to the CNS. Therapeutic Effects:

Prolongs duration of response to levodopa with

end-of-dose motor fluctuations. Decreased signs and

symptoms of Parkinson’s disease.

Pharmacokinetics

Absorption: 35% absorbed following oral administration;

absorption is rapid.

Distribution: Unknown.

Protein Binding: 98%.

Metabolism and Excretion: Minimal amounts

excreted unchanged; highly metabolized followed by

biliary excretion.

Half-life: Initial phase—0.4–0.7 hr; second

phase—2.4 hr.

TIME/ACTION PROFILE (inhibition of COMT)

ROUTE ONSET PEAK DURATION

PO unknown unknown up to 8 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent

nonselective MAO inhibitor therapy; Psychotic disorder.

Use Cautiously in: Hepatic impairment; Concurrent

use of drugs that are metabolized by COMT; OB,

Lactation: Safety not established; Pedi: No identified use

in children.

Adverse Reactions/Side Effects

CNS: NEUROLEPTIC MALIGNANT SYNDROME, agitation, aggressive

behavior, confusion, delirium, disorientation,

dizziness, hallucinations, paranoid ideation, syncope,

urges (gambling, sexual). Resp: pulmonary infiltrates,

pleural effusion, pleural thickening. CV: hypotension.

Derm: melanoma. GI: abdominal pain, colitis, diarrhea,

nausea (during initiation), retroperitoneal fibrosis.

GU: brownish-orange discoloration of urine. MS:

RHABDOMYOLYSIS, dyskinesia. Neuro: dyskinesia.

Interactions

Drug-Drug: Concurrent use with selective MAO inhibitors

is not recommended; both agents inhibit the

metabolic pathways of catecholamines. Concurrent use

of drugs that are metabolized by COMT such as isoproterenol,

epinephrine, norepinephrine, dopamine,

dobutamine, and methyldopa mayqrisk of

tachycardia,qBP, and arrhythmias. Probenecid, cholestyramine,

erythromycin, rifampin, ampicillin,

and chloramphenicol may interfere with biliary elimination

of entacapone; use concurrently with caution.

Route/Dosage

PO (Adults): 200 mg with each dose of levodopa/carbidopa

up to a maximum of 8 times daily.

Availability (generic available)

Tablets: 200 mg. In combination with: levodopa/

carbidopa (Stalevo), see Appendix B.