Abstract
OBJECTIVES: Amantadine reduces liver transaminase levels in some patients with chronic hepatitis C at doses of 200 mg daily and may improve the sustained virological response (SVR) when given with interferon and ribavirin. The primary purpose of the present investigation was to study the safety and toxicity of higher doses of amantadine in subjects who previously failed or were intolerant to interferon. The secondary aim was to test the efficacy of higher dose of amantadine against hepatitis C.
METIIODS: An open-labeled prospective study was conducted starting with amantadine 200 mg daily and increasing to 500 mg daily while monitoring for safety, tox icity, and efficacy. An amantad ine blood level exceeding 1,600 ng/ml was considered toxic requiring dose reduction. The patient's symptoms, laboratory tests, and quality of life were monitored .
RESULTS: One hundred patients enrolled in th e s tud y. Normalization of alanine aminotransferase (ALT) for each dose was as follows: 200 mg (35%), 300 mg (49%), 400 mg (53%), and 500 mg (56%). The incidence of toxic amantadine plasma levels increased with dose, i.e ., 200 mg (0%), 300 mg (6%),400 mg (27%), and 500 mg (49%). The frequency and severity of arthralgia and fatigue improved at all dosages administered. No changes in the occurrence or severity of headache, insomnia, or depression were reported. Serious adverse events included myocardial infarction and suicide attempt. Other side effects in cluded impotence, confusion, alopec ia, and hoarseness.
CONCLUSIONS: Amantadine given at a dose of300 mg daily is safe, and sign ificantly lowers AL T blood levels more than 200 mg daily. The enzyme response rate does not significantly improve above 300 mg, but toxicity increases.
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