Amantadine

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Patients taking amantadine for Parkinson disease have reported falling asleep while engaged in activities of daily living, sometimes without warning. Patients with a concomitant sleep disorder may be at a greater risk. There is insufficient information that dose reduction will eliminate episodes of falling asleep or daytime somnolence.

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), urges to spend money, 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.

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.

Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation).

Visual and auditory hallucinations, delusions, illusions, and paranoia were reported in clinical trials; monitor for the occurrence of these symptoms especially at initiation and after dose increases. Use with caution in patients with uncontrolled psychosis or severe psychoneurosis.

There have been reports of suicidal ideation/attempt and depression in patients with and without a history of psychiatric illness. May exacerbate mental problems in patients with a history of mental illness. Disease-related concerns:

Use with caution in patients with heart failure, peripheral edema, or orthostatic hypotension; dizziness, syncope, orthostatic hypotension, presyncope, postural dizziness, and hypotension have been reported in clinical trials. Dosage reduction may be required.

Use with caution in patients with a history of recurrent and eczematoid dermatitis.

Avoid in untreated angle closure glaucoma.

Use with caution in patients with hepatic impairment; rarely, reversible elevations in transaminases have been reported.

Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established (CDC 2011).

Use with caution in patients with renal impairment; dosage reduction recommended. Use of the extended-release capsule is contraindicated in end-stage renal disease (CrCl 2).

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 susceptible to CNS effects (using 2 divided daily doses of immediate-release products may minimize this effect). These patients may require dosage reductions. Dosage form specific issues:

Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). Other warnings/precautions:

Tolerance has also been reported with long-term use (Zubenko1984).

May cause agitation, anxiety, delirium, delusions, depression, hallucinations, paranoia, parkinsonian crisis, slurred speech, or stupor. Upon discontinuation of amantadine therapy, gradually taper dose.