Publication: Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: Safety and pharmacokinetics
Issued Date
2013-05-28
Resource Type
ISSN
20402058
13596535
13596535
DOI
Other identifier(s)
2-s2.0-84878060062
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Mahidol University
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SCOPUS
Bibliographic Citation
Antiviral Therapy. Vol.18, No.3 (2013), 377-386
Suggested Citation
Sachiko Seo, Janet A. Englund, Jack T. Nguyen, Sasithon Pukrittayakamee, Niklas Lindegardh, Joel Tarning, Paul A. Tambyah, Christian Renaud, Gregory T. Went, Menno D. De Jong, Michael J. Boeckh Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: Safety and pharmacokinetics. Antiviral Therapy. Vol.18, No.3 (2013), 377-386. doi:10.3851/IMP2475 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32331
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Title
Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: Safety and pharmacokinetics
Abstract
Background: Antiviral resistance among influenza A viruses is associated with high morbidity and mortality in immunocompromised hosts. However, treatment strategies for drug-resistant influenza A are not established. A triple-combination antiviral drug (TCAD) regimen consisting of amantadine (AMT), oseltamivir (OSL) and ribavirin (RBV) demonstrated good efficacy in an animal model. Methods: We first analysed the pharmacokinetics (PKs) of TCAD therapy in healthy volunteers. We then performed a pilot study of TCAD therapy in patients undergoing chemotherapy or haematopoietic cell transplantation. AMT (75 mg), OSL (50 mg) and RBV (200 mg) were administered three times a day for 10 days. The safety and PKs of TCAD therapy were monitored. Results: The PKs of TCAD therapy in healthy volunteers was shown to be similar to the PKs of each drug individually from a single dose. In the pilot study, six immunocompromised patients received TCAD therapy and one patient received OSL monotherapy. All but one patient completed 10 days of TCAD therapy without side effects; one patient receiving TCAD was withdrawn from the study because of respiratory failure and ultimately recovered. Viral load was decreased after TCAD therapy, despite the presence of either AMT- or OSL-resistant virus in two cases. One patient with 2009 influenza A/H1N1 receiving OSL monotherapy developed confirmed OSL resistance during treatment. Conclusions: TCAD therapy had similar PKs to each individual antiviral during monotherapy following a single dose and can be administered safely in immunocompromised patients. ©2013 International Medical Press.