Amantadine therapy for chronic hepatitis C: a dose escalation study

Area of Science:

• Hepatology
• Pharmacology
• Virology

Background:

• Amantadine shows potential in managing chronic hepatitis C by reducing liver transaminase levels.
• Previous studies suggest amantadine may enhance sustained virological response (SVR) when combined with interferon and ribavirin.

Purpose of the Study:

• To evaluate the safety and toxicity of escalating amantadine doses (up to 500 mg daily) in patients with chronic hepatitis C.
• To assess the efficacy of higher amantadine doses in treating hepatitis C in patients who failed or were intolerant to interferon therapy.

Main Methods:

• An open-label prospective study involving 100 patients treated with amantadine, starting at 200 mg daily and increasing to 500 mg daily.
• Monitoring of amantadine plasma levels, with toxicity defined as exceeding 1,600 ng/ml, alongside assessment of symptoms, laboratory tests, and quality of life.

Main Results:

• Normalization of alanine aminotransferase (ALT) increased with dose: 35% at 200 mg, 49% at 300 mg, 53% at 400 mg, and 56% at 500 mg.
• Toxic amantadine plasma levels increased significantly with dose, from 0% at 200 mg to 49% at 500 mg.
• Arthralgia and fatigue improved, but serious adverse events like myocardial infarction and suicide attempt were reported.

Conclusions:

• Amantadine 300 mg daily is a safe and effective dose for lowering ALT levels in chronic hepatitis C patients.
• Doses above 300 mg daily do not significantly improve enzyme response rates but are associated with increased toxicity.
• Further research is needed to balance efficacy and safety for amantadine in hepatitis C treatment.