A part-randomized study of intravenous oseltamivir in adolescents and adults

• Published in: European journal of clinical microbiology & infectious diseases Vol. 34; no. 6; pp. 1181 - 1188
• Main Authors: Várkonyi, I., Chappey, C., Giraudon, M., Burleigh, L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2015; Springer Nature B.V
• Subjects: Adolescent; Adolescents; Adult; Aged; Aged, 80 and over; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - pharmacokinetics; Biomedical and Life Sciences; Biomedicine; Blood Chemical Analysis; Critical Illness; Drug dosages; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Female; Hospitalization; Humans; Influenza; Influenza, Human - drug therapy; Influenza, Human - virology; Infusions, Intravenous - adverse effects; Internal Medicine; Male; Medical Microbiology; Middle Aged; Nasal Mucosa - virology; Oral administration; Oseltamivir - administration & dosage; Oseltamivir - adverse effects; Oseltamivir - pharmacokinetics; Patients; Peritoneal dialysis; Pharmacokinetics; Prospective Studies; Renal function; Renal replacement therapy; Reverse Transcriptase Polymerase Chain Reaction; Teenagers; Treatment Outcome; Virus Cultivation; Virus Shedding; Young Adult; United States > US; Continuous Renal Replacement Therapy; Oseltamivir; Reverse Transcription Polymerase Chain Reaction; Influenza; Zanamivir
• ISSN: 0934-9723; 1435-4373
• DOI: 10.1007/s10096-015-2338-5

Seriously ill patients with influenza may be unable to take oral medication. The safety of intravenous oseltamivir was evaluated in adults and adolescents. This prospective, part-randomized study enrolled hospitalized patients aged ≥13 years with clinical or laboratory-confirmed influenza, who started study medication within 144 h of illness onset. Patients with normal renal function received oseltamivir 100 or 200 mg every 12 h for 5 days by slow intravenous infusion. Patients with renal impairment received lower doses, appropriate to the degree of impairment. Blood samples were taken for pharmacokinetics, and nasal swabs were taken to monitor viral shedding and resistance [reverse transcription polymerase chain reaction (RT-PCR) and culture]. Adverse events (AEs) were monitored for 30 days from treatment initiation. Of the 118 patients enrolled, 103 had normal renal function. On day 1, 64 patients had laboratory-confirmed influenza. Ninety-four (80 %) patients completed 5 days of oseltamivir treatment (32 intravenous only). Sixty-eight and 13 patients reported on-treatment AEs and serious AEs (SAEs), respectively (62 and nine during intravenous dosing, respectively). For 33 and six patients, these AEs and SAEs were considered treatment-related (31 and five during intravenous dosing, respectively); 11 patients had AEs causing treatment withdrawal. Five patients died. Adequate systemic exposure to oseltamivir carboxylate (OC) was achieved at the intravenous doses tested. Oseltamivir-resistant viruses (H275Y) were detected in two patients. In seriously ill, hospitalized patients with/without renal impairment, intravenous oseltamivir was not associated with adverse safety findings at the dosages tested and achieved systemic OC exposures at least as high as the approved oral dose.