Amantadine Monotherapy Unsuccessful in Treatment of Chronic Hepatitis
By Brian Boyle, MD
Patients with chronic Hepatitis C have recently enjoyed an improved
efficacy in treatment with pegylated-interferon or combination
therapy with interferon and ribavirin. However, a significant subset
of patients fails these therapies, either because of poor
tolerability or insufficient efficacy against certain HCV genotypes,
and these failures pose a difficult treatment problem.
Amantadine hydrochloride was first suggested as a controversial
treatment option for HCV in 1997, but was reported to be poorly
tolerated with little efficacy. However, these studies were performed
in heterogeneous populations that included both HCV treatment naïve
and experienced patients. In the March 1, 2001 issue of Clinical
Infectious Diseases, Di Martino and others report on a prospective,
pilot study of amantadine hydrochloride monotherapy that was
performed in ten patients with chronic active hepatitis C documented
by histological testing. The enrolled patients had previously failed
to respond to 12 months of interferon (7 patients) or interferon-
ribavirin (3 patients) therapy. Nine were infected with HCV genotype
1. The mean HCV RNA load was 5.8 log10 copies/mL and the serum
alanine aminotransferase (ALT) was 1.5 fold greater than normal in
The patients were given amantadine (100mg orally twice a day)
monotherapy for 12 months. HCV RNA did not become undetectable or
significantly decrease in any patient and, in fact, there was a trend
toward increases in HCV RNA from baseline and to the end of therapy.
Further, while a decrease in ALT levels occurred initially in most
patients, it was generally not sustained.
Amantadine therapy was poorly tolerated in this study with only 2 of
the patients completing the full 12 month treatment course. 4
patients had amantadine therapy discontinued at 3 months due to a
significant increase in ALT levels. Other major adverse events
included vertigo, insomnia,nervousness and depression and led to
study discontinuation in 4 patients.
This failure of amantadine monotherapy in this study confirms the
findings of previous studies and illustrates the need for additional
agents for the treatment of HCV infection.
V Di Martino and others. Treatment of Chronic Hepatitis C with
Amantadine Hydrochloride in Patients Who Had Not Responded to
Previous Interferon-a and/or Ribavirin. Clinical Infectious Diseases.
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