tetano
Editor, Senior Moderator
Antivir Ther. 2012 Dec 21. doi: 10.3851/IMP2475. [Epub ahead of print]
Combination therapy with amantadine, oseltamivir, and ribavirin for influenza A infection: safety and pharmacokinetics.
Seo S, Englund JA, Nguyen JT, Pukrittayakamee S, Lindegardh N, Tarning J, Tambyah PA, Renaud C, Went GT, de Jong MD, Boeckh MJ.
Source
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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, oseltamivir, and ribavirin demonstrated good efficacy in an animal model.
METHODS:
We first analyzed pharmacokinetics of TCAD therapy in healthy volunteers. We then performed a pilot study of TCAD in patients undergoing chemotherapy or hematopoietic cell transplantation. Amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg) were administered three times a day for 10 days. The safety and pharmacokinetics of TCAD therapy were monitored.
RESULTS:
Pharmacokinetics (PK) of TCAD therapy in healthy volunteers was shown to be similar to the PK of each drug individually from a single dose. In the pilot study, six immunocompromised patients received TCAD therapy and one patient received oseltamivir 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 All but one patient completed 10 days of TCAD therapy without side effects; one patient receiving TCAD was withdrawn from the study because of respiratory failure and ultimately recovered.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 amantadine- or oseltamivir- resistant virus in two cases. One patient with 2009 influenza A/H1N1 receiving oseltamivir monotherapy developed confirmed oseltamivir-resistance during treatment.
CONCLUSIONS:
TCAD therapy had similar pharmacokinetics to each individual antiviral during monotherapy following a single dose and can be administered safely in immunocompromised patients.
PMID:
23264438
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23264438
Combination therapy with amantadine, oseltamivir, and ribavirin for influenza A infection: safety and pharmacokinetics.
Seo S, Englund JA, Nguyen JT, Pukrittayakamee S, Lindegardh N, Tarning J, Tambyah PA, Renaud C, Went GT, de Jong MD, Boeckh MJ.
Source
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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, oseltamivir, and ribavirin demonstrated good efficacy in an animal model.
METHODS:
We first analyzed pharmacokinetics of TCAD therapy in healthy volunteers. We then performed a pilot study of TCAD in patients undergoing chemotherapy or hematopoietic cell transplantation. Amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg) were administered three times a day for 10 days. The safety and pharmacokinetics of TCAD therapy were monitored.
RESULTS:
Pharmacokinetics (PK) of TCAD therapy in healthy volunteers was shown to be similar to the PK of each drug individually from a single dose. In the pilot study, six immunocompromised patients received TCAD therapy and one patient received oseltamivir 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 amantadine- or oseltamivir- resistant virus in two cases. One patient with 2009 influenza A/H1N1 receiving oseltamivir monotherapy developed confirmed oseltamivir-resistance during treatment.
CONCLUSIONS:
TCAD therapy had similar pharmacokinetics to each individual antiviral during monotherapy following a single dose and can be administered safely in immunocompromised patients.
PMID:
23264438
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23264438