Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics
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...
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| Veröffentlicht in: | Antiviral therapy 2013-01, Vol.18 (3), p.377-386 |
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| creator | SEO, Sachiko ENGLUND, Janet A BOECKH, Michael J NGUYEN, Jack T PUKRITTAYAKAMEE, Sasithon LINDEGARDH, Niklas TARNING, Joel TAMBYAH, Paul A RENAUD, Christian WENT, Gregory T DE JONG, Menno D |
| description | 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.
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.
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 All but one patient completed 10 days of TCAD therapy without side effects; one patient receiving TCAD was withdrawn from the study because of respiratory failure and ultimately recovered.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.
TCAD therapy had similar PKs to each individual antiviral during monotherapy following a single dose and can be administered safely in immunocompromised patients. |
| doi_str_mv | 10.3851/IMP2475 |
| format | Article |
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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.
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.
TCAD therapy had similar PKs to each individual antiviral during monotherapy following a single dose and can be administered safely in immunocompromised patients.</description><identifier>ISSN: 1359-6535</identifier><identifier>EISSN: 2040-2058</identifier><identifier>DOI: 10.3851/IMP2475</identifier><identifier>PMID: 23264438</identifier><language>eng</language><publisher>London: International Medical Press</publisher><subject>Adult ; Amantadine - adverse effects ; Amantadine - pharmacokinetics ; Amantadine - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Human viral diseases ; Humans ; Immunocompromised Host ; Infectious diseases ; Influenza A virus - genetics ; Influenza, Human - drug therapy ; Influenza, Human - virology ; Male ; Medical sciences ; Mutation ; Oseltamivir - adverse effects ; Oseltamivir - pharmacokinetics ; Oseltamivir - therapeutic use ; Pharmacology. Drug treatments ; Pilot Projects ; Ribavirin - adverse effects ; Ribavirin - pharmacokinetics ; Ribavirin - therapeutic use ; Viral diseases ; Viral diseases of the respiratory system and ent viral diseases ; Viral Load ; Young Adult</subject><ispartof>Antiviral therapy, 2013-01, Vol.18 (3), p.377-386</ispartof><rights>2014 INIST-CNRS</rights><rights>2013 International Medical Press 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c432t-7d45be437fbdbb8eb35e8867264ae05a3c470bc877b93f743e216deeab22c6c03</citedby><cites>FETCH-LOGICAL-c432t-7d45be437fbdbb8eb35e8867264ae05a3c470bc877b93f743e216deeab22c6c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27423264$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23264438$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SEO, Sachiko</creatorcontrib><creatorcontrib>ENGLUND, Janet A</creatorcontrib><creatorcontrib>BOECKH, Michael J</creatorcontrib><creatorcontrib>NGUYEN, Jack T</creatorcontrib><creatorcontrib>PUKRITTAYAKAMEE, Sasithon</creatorcontrib><creatorcontrib>LINDEGARDH, Niklas</creatorcontrib><creatorcontrib>TARNING, Joel</creatorcontrib><creatorcontrib>TAMBYAH, Paul A</creatorcontrib><creatorcontrib>RENAUD, Christian</creatorcontrib><creatorcontrib>WENT, Gregory T</creatorcontrib><creatorcontrib>DE JONG, Menno D</creatorcontrib><title>Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics</title><title>Antiviral therapy</title><addtitle>Antivir Ther</addtitle><description>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.
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.
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.
TCAD therapy had similar PKs to each individual antiviral during monotherapy following a single dose and can be administered safely in immunocompromised patients.</description><subject>Adult</subject><subject>Amantadine - adverse effects</subject><subject>Amantadine - pharmacokinetics</subject><subject>Amantadine - therapeutic use</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Drug Resistance, Viral</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunocompromised Host</subject><subject>Infectious diseases</subject><subject>Influenza A virus - genetics</subject><subject>Influenza, Human - drug therapy</subject><subject>Influenza, Human - virology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mutation</subject><subject>Oseltamivir - adverse effects</subject><subject>Oseltamivir - pharmacokinetics</subject><subject>Oseltamivir - therapeutic use</subject><subject>Pharmacology. Drug treatments</subject><subject>Pilot Projects</subject><subject>Ribavirin - adverse effects</subject><subject>Ribavirin - pharmacokinetics</subject><subject>Ribavirin - therapeutic use</subject><subject>Viral diseases</subject><subject>Viral diseases of the respiratory system and ent viral diseases</subject><subject>Viral Load</subject><subject>Young Adult</subject><issn>1359-6535</issn><issn>2040-2058</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU2LFDEQhoMo7riK_0ByET3Yms9OjwdhGfxYWNGDnkMlXe1Eu5PZJL0y_np7dsdVT_VCPTxV8BLymLOXstP81fnHz0IZfYesBFOsEUx3d8mKS71uWi31CXlQynfGRLdm7D45EVK0SsluReZNmlyIUEOKtG4xw25Pf4a6pTBBrNCHiC9oKjhWmMJVyBRiT3NwsOQQ6ZAyDXEYZ4y_gJ4dMvqD7DUtMGDdX_O7LeQJfPqx2Grw5SG5N8BY8NFxnpKv795-2XxoLj69P9-cXTReSVEb0yvtUEkzuN65Dp3U2HWtWZ4HZBqkV4Y53xnj1nIwSqLgbY8ITgjfeiZPyZsb7252E_YeY80w2l0OE-S9TRDs_5sYtvZburJyzYXgB8HzoyCnyxlLtVMoHscRIqa5WK5bxiXTSi_osxvU51RKxuH2DGf2UJI9lrSQT_796pb708oCPD0CUDyMQ4boQ_nLGXWNyt8ptpzd</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>SEO, Sachiko</creator><creator>ENGLUND, Janet A</creator><creator>BOECKH, Michael J</creator><creator>NGUYEN, Jack T</creator><creator>PUKRITTAYAKAMEE, Sasithon</creator><creator>LINDEGARDH, Niklas</creator><creator>TARNING, Joel</creator><creator>TAMBYAH, Paul A</creator><creator>RENAUD, Christian</creator><creator>WENT, Gregory T</creator><creator>DE JONG, Menno D</creator><general>International Medical Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T2</scope><scope>7U2</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20130101</creationdate><title>Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics</title><author>SEO, Sachiko ; ENGLUND, Janet A ; BOECKH, Michael J ; NGUYEN, Jack T ; PUKRITTAYAKAMEE, Sasithon ; LINDEGARDH, Niklas ; TARNING, Joel ; TAMBYAH, Paul A ; RENAUD, Christian ; WENT, Gregory T ; DE JONG, Menno D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-7d45be437fbdbb8eb35e8867264ae05a3c470bc877b93f743e216deeab22c6c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Amantadine - adverse effects</topic><topic>Amantadine - pharmacokinetics</topic><topic>Amantadine - therapeutic use</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Drug Resistance, Viral</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunocompromised Host</topic><topic>Infectious diseases</topic><topic>Influenza A virus - genetics</topic><topic>Influenza, Human - drug therapy</topic><topic>Influenza, Human - virology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mutation</topic><topic>Oseltamivir - adverse effects</topic><topic>Oseltamivir - pharmacokinetics</topic><topic>Oseltamivir - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>Pilot Projects</topic><topic>Ribavirin - adverse effects</topic><topic>Ribavirin - pharmacokinetics</topic><topic>Ribavirin - therapeutic use</topic><topic>Viral diseases</topic><topic>Viral diseases of the respiratory system and ent viral diseases</topic><topic>Viral Load</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SEO, Sachiko</creatorcontrib><creatorcontrib>ENGLUND, Janet A</creatorcontrib><creatorcontrib>BOECKH, Michael J</creatorcontrib><creatorcontrib>NGUYEN, Jack T</creatorcontrib><creatorcontrib>PUKRITTAYAKAMEE, Sasithon</creatorcontrib><creatorcontrib>LINDEGARDH, Niklas</creatorcontrib><creatorcontrib>TARNING, Joel</creatorcontrib><creatorcontrib>TAMBYAH, Paul A</creatorcontrib><creatorcontrib>RENAUD, Christian</creatorcontrib><creatorcontrib>WENT, Gregory T</creatorcontrib><creatorcontrib>DE JONG, Menno D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Safety Science and Risk</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antiviral therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SEO, Sachiko</au><au>ENGLUND, Janet A</au><au>BOECKH, Michael J</au><au>NGUYEN, Jack T</au><au>PUKRITTAYAKAMEE, Sasithon</au><au>LINDEGARDH, Niklas</au><au>TARNING, Joel</au><au>TAMBYAH, Paul A</au><au>RENAUD, Christian</au><au>WENT, Gregory T</au><au>DE JONG, Menno D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics</atitle><jtitle>Antiviral therapy</jtitle><addtitle>Antivir Ther</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>18</volume><issue>3</issue><spage>377</spage><epage>386</epage><pages>377-386</pages><issn>1359-6535</issn><eissn>2040-2058</eissn><abstract>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.
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.
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.
TCAD therapy had similar PKs to each individual antiviral during monotherapy following a single dose and can be administered safely in immunocompromised patients.</abstract><cop>London</cop><pub>International Medical Press</pub><pmid>23264438</pmid><doi>10.3851/IMP2475</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Amantadine - adverse effects Amantadine - pharmacokinetics Amantadine - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Drug Resistance, Viral Drug Therapy, Combination Female Human viral diseases Humans Immunocompromised Host Infectious diseases Influenza A virus - genetics Influenza, Human - drug therapy Influenza, Human - virology Male Medical sciences Mutation Oseltamivir - adverse effects Oseltamivir - pharmacokinetics Oseltamivir - therapeutic use Pharmacology. Drug treatments Pilot Projects Ribavirin - adverse effects Ribavirin - pharmacokinetics Ribavirin - therapeutic use Viral diseases Viral diseases of the respiratory system and ent viral diseases Viral Load Young Adult |
| title | Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics |
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