Amantadine scientific update |
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Dig Dis Sci. 2007 Mar 31;
Riley TR 3rd, Taheri MR.
Department of Medicine, Penn State University, The Hershey Medical Center, Hershey, Pennsylvania, USA.
Long-Term Treatment with the Combination of Amantadine and Ribavirin in Hepatitis C Nonresponders. A Case Series.
In this report, we describe five cases of chronic hepatitis C that have been treated with the combination of
amantadine and ribavirin for an average of 44 months, emphasizing one case where the patient showed improvement in
liver biopsy after treatment, worsening on removal, then a repeated improvement with re-initiation. The five
patients in this report belong to a pool of sixty patients from a 6 month pilot study using amantadine and
ribavirin where treatment was subsequently continued. The mean ALT was 82.8+/-32 U/L pre-treatment and 33.8+/-17.3
U/L post-treatment (p=0.02). The mean Knodell score was 7+/-1 pre-treatment and 3.6+/-1.5 post-treatment (p=0.13).
The mean viral load was 584,155+/-248,027 lU/ml pre-treatment and 225,878+/-190,143 IU/ml post-treatment (p=0.05).
In this case series we provide provocative data on the long-term use of ribavirin and amantadine in the HCV
non-responder.
J Clin Virol. 2007 May;39(1):54-8. Epub 2007 Apr 3.
Calanca LN, Fehr T, Jochum W, Fischer-Vetter J, Mullhaupt B, Wuthrich RP, Ambuhl PM.
Department of Nephrology, University Hospital, Ramistrasse 100, CH 8091 Zurich, Switzerland.
Combination therapy with ribavirin and amantadine in renal transplant patients with chronic hepatitis C virus infection is not superior to ribavirin alone.
BACKGROUND: Standard treatment of chronic hepatitis C virus (HCV) infection based on interferon is not an option in
renal transplant recipients due to the high risk of acute allograft rejection. OBJECTIVES: To assess efficacy and
tolerability of combined treatment with ribavirin and amantadine regarding viral clearance, normalization of liver
enzymes, and improvement of HCV-related hepatopathy and graft nephropathy in HCV-RNA-positive renal transplant
patients. STUDY DESIGN: Prospective randomized controlled study comparing ribavirin, 1000mg daily (n=7), versus
ribavirin, 1000mg, in combination with amantadine, 200mg daily (n=8), for 12 months, versus no therapy (controls,
n=26). Results were evaluated by intention-to-treat analysis. RESULTS: No relevant differences among treatment
groups were found regarding liver enzymes, HCV viremia, liver histology and renal parameters. However, antiviral
treatment was limited by anemia, resulting in premature withdrawal from therapy and requiring substitution with
recombinant erythropoietin in most patients. The best predictor for tolerability of active treatment was a
creatinine clearance rate>50ml/min. CONCLUSIONS: Addition of amantadine to ribavirin seems not to be superior to
ribavirin monotherapy in renal transplant patients with chronic replicating HCV infection. However, this may be
explained in part by the poor tolerability of both ribavirin and amantadine in patients with impaired renal
function, resulting in drop-outs and subtherapeutic drug dosage.
Semin Respir Crit Care Med. 2007 Apr;28(2):144-58.
Lynch JP 3rd, Walsh EE.
Division of Pulmonary, Critical Care Medicine, and Hospitalists, Department of Internal Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Influenza: evolving strategies in treatment and prevention.
Influenza A and B are important causes of respiratory illness in all age groups. Influenza causes seasonal
outbreaks globally, and (rarely) pandemics. In the United States, seasonal influenza epidemics account for >
200,000 hospitalizations and > 30,000 deaths annually. More than 90% of deaths are in the elderly. The toll is
considerably higher during pandemics. Clinical features of influenza infection overlap with other respiratory
pathogens (particularly viruses). The diagnosis is often delayed due to low suspicion and the limited use of
specific diagnostic tests. Rapid diagnostic tests are widely available and allow detection of influenza antigen in
respiratory secretions within 1 hour; however, sensitivity ranges from 40 to 80%. Currently, four drugs are
available to treat or prevent influenza. These include the adamantanes (i.e., amantadine and rimantadine) and the
neuraminidase inhibitors (i.e., oseltamivir and zanamivir). Adamantanes are active against influenza A but not
influenza B. However, recent emergence of adamantane resistance has rendered these agents ineffective. Hence,
adamantanes are not currently recommended in the United States. The neuraminidase inhibitors (NAIs) are effective
in treating influenza A or B, and for prophylaxis in selected adults and children. Resistance to NAIs is rare, but
influenza strains resistant to oseltamivir have been detected. Vaccines are the cornerstone of influenza control.
Currently, trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) are available. These
agents reduce mortality and morbidity in high-risk patients (i.e., the elderly or patients with comorbidities), and
expanding the use of vaccines to healthy children and adults reduces the incidence of influenza, pneumonia, and
hospitalizations due to respiratory illnesses in the community.
Can J Neurol Sci. 2007 Mar;34 Suppl 1:S118-24.
Freedman M.
Division of Neurology and Rotman Research Institute, Baycrest.
Frontotemporal dementia: recommendations for therapeutic studies, designs, and approaches.
Frontotemporal dementia (FTD) is one of three neurobehavioural syndromes produced by frontotemporal lobar
degeneration. Despite the importance of FTD as a cause of dementia, especially in younger age groups, and a
rationale for therapies targeting serotonergic and dopaminergic systems, there have been no large scale treatment
trials in FTD. Moreover, there is no consensus on standards to facilitate comparison across therapeutic trials.
This paper reviews the literature on therapeutic trials in FTD and outlines general recommendations for standards
related to the development of future treatment studies in this disorder. Drugs tested in FTD include trazodone,
galantamine, idazoxan, lithium plus fluoxetine, lithium plus paroxetine, SSRIs, 1-deprenyl, moclobemide,
methylphenidate, piracetam, rivastigmine, donepezil, olanzapine, risperidone, amantadine, guanfacine, allopurinol,
and bromocriptine. Improvement has been reported in FTD for all drugs except piracetam, guanfacine and galantamine,
although there was improvement on galantamine in primary progressive aphasia. Whereas improvement has been reported
for paroxetine and other SSRIs, as well as idazoxan and methylphenidate, paroxetine and idazoxan have also been
reported to cause a decline in function, and a marginally significant decline has been reported for
methylphenidate. In addition, patients with Pick's disease, which is part of the spectrum of frontotemporal lobar
degeneration, showed improvement on calcium EDTA. Six studies are double-blind placebo-controlled trials: two
reports of cases using idazoxan and group trials using trazodone, paroxetine, galantamine and methylphenidate. It
is recommended that experts in FTD arrive at a consensus to define standards for all clinical trials in FTD. These
should include standards for diagnostic criteria, tests of severity, experimental design, and outcome measures.
Trends Pharmacol Sci. 2007 May 2;
De Clercq E, Neyts J.
Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Avian influenza A (H5N1) infection: targets and strategies for chemotherapeutic intervention.
In an avian flu pandemic, which drugs could be used to treat or prevent infection with influenza A (H5N1) virus?
Foremost are the viral neuraminidase inhibitors oseltamivir and zanamivir, which have already been used to treat
human influenza A (H1N1 and H3N2) and B virus infections. The use of the M2 ion channel blockers amantadine and
rimantadine is compounded by the rapid development of drug resistance. Although formally approved for other
indications (i.e. treatment of hepatitis C), ribavirin and pegylated interferon might also be useful for
controlling avian flu. Combined use of the currently available drugs should be taken into account and attempts
should be made to develop new strategies directed at unexplored targets such as the viral proteins hemagglutinin,
the viral polymerase (and endonuclease) and the non-structural protein NS1. As has been shown for other viral
infections, RNA interference could be a powerful means with which to suppress the replication of avian H5N1.
Avian Dis. 2007 Mar;51(1 Suppl):194-200.
Buranathai C, Amonsin A, Chaisigh A, Theamboonlers A, Pariyothorn N, Poovorawan Y.
Department of Livestock Development, 69/1 Payathai Road, Rajathevi, Bangkok 10400, Thailand.
Surveillance activities and molecular analysis of H5N1 highly pathogenic avian influenza viruses from Thailand, 2004-2005.
Avian influenza (AI) outbreaks were first reported in Thailand in January 2004. In the past 2 yr, AI viruses have
caused three epidemic waves. Disease prevention and control in all aspects have been actively carried out. Active
and passive surveillance based on clinical observation and laboratory analysis were intensively conducted, as well
as monitoring of genetic variation of the viruses. H5N1 viruses isolated from different avian species from
different cases and locations were selected. We have sequenced specific genes (HA, NA, M, Ns, and part of PB2
genes) of 58 H5N1 isolates, as well as whole genome sequencing of 21 Thai influenza A (H5N1) viruses isolated
during the 2004-2005 outbreak. Cluster analysis study showed that AI isolates were identified as highly pathogenic
avian influenza (HPAI) and belonged to genotype Z. The virus had a multiple basic amino acid motif at the cleavage
site of HA, deletions in the NA stalk region, a five amino acid deletion in the NS1 gene, and genetic markers for
amantadine resistance in the M2 gene. All 58 H5N1 isolates were closely related and grouped into the same cluster,
together with isolates from wild birds, cats, tigers, and humans. Phylogenetic analysis also revealed that Thai
isolates were in the same cluster as Vietnamese isolates but aligned in a different cluster from Indonesian, Hong
Kong, and Chinese viruses. In addition, genetic analysis showed that most avian influenza virus (AIV) isolates from
Thailand had no major genetic changes in each gene such as HA (HA cleavage site, receptor binding site, N-link
glycosylation site), NA (NA stalk region, oseltamivir resistance marker), M (the amantadine resistance marker, host
specificity site), NS (five amino acid deletion site), and PB2 (host specificity site). All Thai poultry isolates
contained the amantadine resistance marker while none of them had the oseltamivir resistance marker. To this end,
the molecular characterization of H5N1 viruses from Thailand showed that there were no significant point mutations
in the critical regions, and there was no evidence of changes in the viruses that indicate they are capable of
sustained human-to-human transmission.
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Drug category:anti-avian drugs
 Amantadine scientific update
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