Pharmacokinetics and Pharmacodynamics of Conventional-Dose vs Triple-Dose Oseltamivir in Severely Immunocompromised Children With Influenza

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Open Forum Infect Dis. 2019 Oct 23;6(10):ofz430. doi: 10.1093/ofid/ofz430. eCollection 2019 Oct. Pharmacokinetics and Pharmacodynamics of Conventional-Dose vs Triple-Dose Oseltamivir in Severely Immunocompromised Children With Influenza.

Bautista F¹, Engelhard D², Rizzari C³, Baka M⁴, Saavedra-Lozano J⁵, Lopez-Medina E⁶, Nasmyth-Miller C⁷, Hern?ndez-S?nchez J⁷, Sturm S⁸.
Author information

1 Pediatric Hematology, Oncology and Stem Cell Transplantation Department, Hospital Infantil Universitario Ni?o Jes?s, Madrid, Spain. 2 Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 3 Pediatric Hematology-Oncology Unit, Department of Pediatrics, MBBM Foundation, ASST-Monza, University of Milano-Bicocca, Monza, Italy. 4 Department of Pediatric Oncology, Aglaia Kyriakou Children's Hospital, Athens, Greece. 5 Infectious Disease Unit, Department of Pediatrics, Hospital General Universitario Gregorio Mara??n, Madrid, Spain. 6 Department of Pediatrics, Universidad del Valle, Centro M?dico Imbanaco and Centro de Estudios en Infectolog?a Pedi?trica, Cali, Colombia. 7 Roche Products Ltd, Welwyn Garden City, UK. 8 Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development, Basel, Switzerland.

Abstract

This randomized phase 1b study evaluated the pharmacokinetics/pharmacodynamics of conventional-dose (30-75 mg twice daily [BID]) vs triple-dose (90-225 mg BID; weight-adjusted) oseltamivir for treatment of influenza in severely immunocompromised children <13 years. Oseltamivir carboxylate (OC) C_max and AUC_0-12h were ~2-fold higher with triple-dose vs conventional-dose oseltamivir. Increased dose/exposure of oseltamivir/OC did not improve virological outcomes or reduce viral resistance. Median time to cessation of viral shedding was similar with triple-dose and conventional-dose oseltamivir (150.7 vs 157.1 hours, respectively); median time to alleviation of baseline fever was longer with conventional-dose oseltamivir (28.4 vs 11.3 hours). No new safety signals were identified.
? The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.


KEYWORDS:

children; clinical trial; immunocompromised; influenza; oseltamivir

PMID: 31660381 PMCID: PMC6809794 DOI: 10.1093/ofid/ofz430
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