Anti-Parkinson's Agent (COMT Inhibitor)

Adjunct to levodopa/carbidopa therapy in patients with idiopathic Parkinson's disease who experience "wearing-off" symptoms at the end of a dosing interval

C

Not recommended

Hypersensitivity to the drug or any of its components

Patient should not be treated concomitantly with entacapone and a nonselective MAO inhibitor. Orthostatic hypotension may be increased in patients on dopaminergic therapy in Parkinson's disease.

>10%:

Gastrointestinal: Nausea (14%)

Neuromuscular & skeletal: Dyskinesia (25%), placebo (15%)

1% to 10%:

Central nervous system: Dizziness (8%), fatigue (6%), hallucinations (4%), anxiety (2%), somnolence (2%), agitation (1%)

Cardiovascular: Orthostatic hypotension (4.3%), syncope (1.2%)

Dermatologic: Purpura (2%)

Gastrointestinal: Diarrhea (10%), abdominal pain (8%), constipation (6%), vomiting (4%), dry mouth (3%), dyspepsia (2%), flatulence (2%), gastritis (1%), taste perversion (1%)

Genitourinary: Brown-orange urine discoloration (10%)

Neuromuscular & skeletal: Hyperkinesia (10%), hypokinesia (9%), back pain (4%), weakness (2%)

Miscellaneous: Increased sweating (2%), bacterial infection (1%)

Respiratory: Dyspnea (3%)

<1%: Hyperpyrexia and confusion (resembling neuroleptic malignant syndrome), pulmonary fibrosis, rhabdomyolysis, retroperitoneal fibrosis

Note: Approximately 14% of the 603 patients given entacapone in the double-blind, placebo-controlled trials discontinued treatment due to adverse events compared to 9% of the 400 patients who received placebo.

There have been no reported cases of intentional or accidental overdose with this drug. COMT inhibition by entacapone treatment is dose-dependent.

Cardiac effects with drugs metabolized by COMT (eg, epinephrine, isoproterenol, dopamine, apomorphine, bitolterol, dobutamine, methyldopa) increased other CNS depressants; nonselective MAOIs are not recommended; chelates iron. Caution with drugs that interfere with glucuronidation, intestinal, biliary excretion, intestinal beta-glucuronidase (eg, probenecid, cholestyramine, erythromycin, chloramphenicol, rifampicin, ampicillin).

Entacapone is a reversible and selective inhibitor of catechol-O-methyltransferase (COMT). When entacapone is taken with levodopa, the pharmacokinetics are altered, resulting in more sustained levodopa serum levels compared to levodopa taken alone. The resulting levels of levodopa provide for increased concentrations available for absorption across the blood-brain barrier, thereby providing for increased CNS levels of dopamine, the active metabolite of levodopa.

Onset of action: Rapid

Peak effect: 1 hour

Absorption: Rapid

Distribution: V_d: 20 L after an I.V. dose at steady-state

Protein binding: 98% mainly to albumin

Metabolism: Isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer

Bioavailability: 35%

Half-life: 0.4-0.7 hours based on B-phase; 2.4 hours based on Y-phase

Time to peak serum concentration: 1 hour

Elimination: 10% in urine, 90% in feces

Adults: Oral: 200 mg dose, up to a maximum of 8 times/day; maximum daily dose: 1600 mg/day. Always administer with levodopa/carbidopa. To optimize therapy, the levodopa/carbidopa dosage must be reduced, usually by 25%. This reduction is usually necessary when the patient is taking more than 800 mg of levodopa daily.

Dosage adjustment in hepatic impairment: Treat with caution and monitor carefully; AUC and C_max can be possibly doubled

Can take with or without food

Always administer in association with levodopa/carbidopa; can be combined with both the immediate and sustained release formulations of levodopa/carbidopa. Can be taken with or without food. Should not be abruptly withdrawn from patient's therapy due to significant worsening of symptoms.

Signs and symptoms of Parkinson's disease; liver function tests, blood pressure, patient's mental status

No information available to require special precautions

Dopaminergic therapy in Parkinson's disease (ie, treatment with levodopa) is associated with orthostatic hypotension. Entacapone enhances levodopa bioavailability and may increase the occurrence of hypotension/syncope in the dental patient. The patient should be carefully assisted from the chair and observed for signs of orthostatic hypotension.

Take only as prescribed; can be taken with or without food. Possible nausea, hallucinations, and change in color of urine (not clinically relevant) may occur. Do not drive a car or operate other complex machinery until there is sufficient experience with entacapone. Do not withdraw medication unless advised by healthcare professional.

Tablet: 200 mg