No beneficial effects of amantadine in treatment of chronic hepatitis C patients.
BACKGROUND
Benefit of adding amantadine to antiviral therapy for hepatitis C is controversial.


OBJECTIVE
We aimed to examine whether such policy enhances sustained viral response in treatment-naïve patients.


METHODS
297 naïve hepatitis C patients were randomized for treatment with amantadine 200mg or placebo, combined with weight-based ribavirin and 12-day high-dose interferon alpha-2b induction therapy, followed by PEG-interferon alpha-2b (1.5 microg/kg/week up to 26 weeks and thereafter, 1.0 microg/kg/week until week 52). Treatment was discontinued if hepatitis C virus (HCV) RNA was positive at week 24.


RESULTS
49% of patients were (former) drug users. Genotype 1 occurred in 45%, high viral load in 70% and severe fibrosis/cirrhosis in 32%, without differences between amantadine or placebo groups. 90 patients prematurely discontinued treatment, mainly because of grade 3 or 4 toxicity. Intention-to-treat analysis revealed sustained viral response in 47% and 51% of amantadine and placebo groups (p=0.49). Amantadine did not enhance sustained viral response in patients with genotype 1 or high viral load nor did it improve primary non-response, breakthrough or relapse rates. Genotype non-1 and lower pre-treatment gamma GT levels were independent predictors for sustained viral response.


CONCLUSIONS
Adding amantadine to antiviral therapy of previously untreated chronic hepatitis C patients has no beneficial effects.
van Soest
Hanneke
H
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands.
van der Schaar
Peter J
PJ
Koek
Ger H
GH
de Vries
Richard A
RA
van Ooteghem
Nancy A
NA
van Hoek
Bart
B
Drenth
Joost P H
JP
Vrolijk
Jan M
JM
Lieverse
Rob J
RJ
Houben
Peter
P
van der Sluys Veer
Annet
A
Siersema
Peter D
PD
Schipper
Marguerite E I
ME
van Erpecum
Karel J
KJ
Boland
Greet J
GJ
D000328:Adult; D000547:Amantadine / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D057194:Intention to Treat Analysis; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000547:Amantadine; C417083:peginterferon alfa-2b