Entacapone

Abnormal thinking and behavior changes have been reported and may include aggressive behavior, agitation, confusion, delirium, delusions, disorientation, paranoid ideation, and psychotic-like behavior.

Has been associated with delayed development of diarrhea (usual onset after 4 to 12 weeks); use with caution in patients with lower gastrointestinal disease or an increased risk of dehydration. Diarrhea may be a sign of drug-induced colitis (primarily lymphocytic). Monitor for weight loss. Discontinue use with prolonged diarrhea.

New-onset or exacerbation of preexisting dyskinesia may occur when used as an adjunct to levodopa. Decreasing the dose of levodopa may ameliorate these side effects in some cases.

May cause hallucinations.

Compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), intense urges to spend money uncontrollably, and other intense urges have been reported. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.

Risk for melanoma development is increased in Parkinson disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed. The Canadian labeling contraindicates use in patients with suspicious, undiagnosed skin lesions or history of melanoma.

Entacapone, in conjunction with other drug therapy that alters brain biogenic amine concentrations (eg, MAO inhibitors, SSRIs), has been associated with a syndrome resembling neuroleptic malignant syndrome (hyperpyrexia and confusion - some fatal) on abrupt withdrawal or dosage reduction. Concomitant use of entacapone and nonselective MAO inhibitors should be avoided.

May cause orthostatic hypotension and syncope.

Dopaminergic agents from the ergot class have been associated with fibrotic complications, such as retroperitoneal fibrosis, pulmonary infiltrates or pleural effusion and thickening. These complications may resolve when the drug is discontinued, but complete resolution does not always occur. It is unknown whether nonergot, pro-dopaminergic agents like entacapone confer this risk.

Severe rhabdomyolysis has been reported with use.

Patients have reported falling asleep while engaging in activities of daily living; this has been reported to occur without significant warning signs and may occur as late as up to 1 year after initiation of treatment. Monitor for daytime somnolence or preexisting sleep disorder. Use caution in the presence of sleep disorders, with other CNS depressants, sedating agents, psychoactive drugs or ethanol. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Disease-related concerns:

The Canadian product labeling notes to use with caution in patients with cardiovascular disease, including a history of myocardial infarction (MI) and arrhythmias; MI and other ischemic adverse events have been observed in clinical trials.

Use with caution in patients with hepatic impairment or biliary obstruction. The Canadian labeling contraindicates use in hepatic impairment.

Avoid use in patients with major psychotic disorder due to the risk of exacerbating psychosis. Many treatments for psychosis may exacerbate the symptoms of Parkinson disease and may also decrease the effectiveness of entacapone. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Effects with other sedative drugs or ethanol may be potentiated. Other warnings/precautions:

Do not withdraw therapy abruptly.

Urine may appear dark in color (brownish orange) during therapy.