Clinical Question: Is amantadine effective in the treatment of hepatitis C in patients who are not candidates for or who fail interferon therapy?

Setting: Outpatient (specialty)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: Investigators enrolled 152 patients (including seven children) with confirmed hepatitis C, abnormal liver enzyme levels, hepatitis C RNA in the blood, and abnormal liver histology in whom interferon was not effective, tolerated, or indicated. Patients were randomized (allocation may not have been concealed) using a complex scheme that balanced the two groups by all characteristics. They received amantadine in a dosage of 100 mg twice daily for 12 months or placebo for six months followed by the same dosage of amantadine for an additional six months (children were given a lower dosage).

After six months, the levels of serum alanine transaminase (ALT) dropped from an average of 106 U per I (106 U per L) to 77.5 U per I (77.5 U per L; P = .08), with 25 percent of treated patients achieving normal ALT levels. The placebo-treated patients experienced no change; however, these patients had a similar decrease when switched to amantadine after six months. With regard to virologic response, RNA levels were negative in 9 percent of patients after six months of therapy. After 12 months, that percentage increased to 11 percent, but six months after discontinuation of amantadine, the levels remained negative in only 6.8 percent of patients. Unfortunately, symptom surveys were not affected by therapy. Quality of life also was not affected, except on the social scale, in patients taking amanatadine for 12 months instead of six months (P = .02). Despite the common intolerance of amantadine at this dosage, almost every patient (92 percent) completed the study.

Bottom Line: Amantadine reduces biochemical markers in patients with hepatitis C but has little effect on symptoms or quality of life in patients for whom interferon is ineffective or not tolerated. (Level of Evidence: 1b)