Concurrent use with hydrochlorothiazide or triamterene can reduce renal clearance of amantadine, with subsequent increase in plasma amantadine and possible toxicity. Mental status changes have been reported after co-trimoxazole was administered to a patient taking amantadine. Although it is not clear which drug in co-trimoxazole may be responsible, trimethoprim and amantadine both undergo tubular secretion. As a result, each drug can interfere with the renal clearance of the other. Trimethoprim should be used cautiously in patients receiving therapy with amantadine.
Effects can appear after a few hours or several days of therapy, or after an increase in dosage.
Although effects are generally mild, they can be worse or more disconcerting for elderly patients. Orthostatic hypotension and possible congestive heart failure can occur during chronic therapy with amantadine. Some of these problems may be due to anticholinergic effects and will respond to dose reduction. Anticholinergic-like effects from amantadine use are more likely to occur in patients with who may have increased plasma concentrations of the drug such as those with renal dysfunction or in the elderly. They also can include blurred vision and urinary retention.