Levodopa

[Canadian Boxed Warning]: Patients have reported falling asleep while engaging in activities of daily living including the driving of a car; in some cases, these events have occurred without significant warning signs. Monitor for daytime somnolence or preexisting sleep disorder; discontinue if significant daytime sleepiness or episodes of falling asleep occur. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive agents. Effects with other sedative drugs or ethanol may be potentiated.

Hypersensitivity reactions may occur in susceptible patients.

Dopamine agonists used for Parkinson disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.

May increase human growth hormone levels.

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. Disease-related concerns:

Use with caution in patients with cardiovascular disease (MI, atrial, nodal, or ventricular arrhythmias); initiate in a monitored setting. Use is contraindicated in decompensated cardiovascular disease.

Use with caution in patients with diabetes mellitus; monitor blood glucose frequently. Antidiabetic agents may require dose adjustment.

Use with caution in patients with chronic wide-angle glaucoma; monitor IOP carefully. Use is contraindicated in patients with angle-closure glaucoma.

Use with caution in patients with hepatic impairment. Use is contraindicated in decompensated hepatic disease.

Use with caution in patients with peptic ulcer disease.

Use with extreme caution in patients with a history of psychotic disorders; observe patients closely for development of depression with concomitant suicidal tendencies. May also cause hallucinations and confusion.

Use with caution in patients with renal impairment. Use is contraindicated in decompensated renal disease.

Use with caution in patients with a history of seizure disorder. 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. Special populations:

Use with caution in the elderly; may be more sensitive to CNS effects of levodopa.

Continue therapy as close to surgical procedures as possible in patients requiring general anesthesia (excluding halothane-risk of blood pressure fluctuations and/or arrhythmias; discontinue benserazide/levodopa 12 to 48 hours before procedure); resume therapy postoperatively with a gradual increase in dose up to that established preoperatively.

Use is contraindicated in patients Other warnings/precautions:

May induce dopaminergic dysregulation syndrome resulting in excessive use of levodopa/benserazide beyond prescribed doses, particularly in males with early onset Parkinson disease (Giovannoni 2000); may lead to cognitive and behavioral disturbances. Monitor for excessive use if cognitive/behavioral disturbances develop.

Not indicated in management of intention tremor, Huntington's chorea, or drug-induced extrapyramidal symptoms. Administer in careful increments and observe closely for development of abnormal involuntary movements.

Avoid abrupt withdrawal of therapy; dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome (NMS) on abrupt withdrawal or significant dosage reduction after long-term use. Withdraw therapy gradually and monitor closely; symptomatic patients should be treated appropriately and if necessary resumption of benserazide/levodopa therapy may be considered.