Oseltamivir in seasonal influenza: cumulative experience in low- and high-risk patients

Abstract

Seasonal influenza viruses cause annual disease epidemics that affect individuals at low and high risk for secondary illnesses. Influenza vaccines are widely used in high-risk patients to prevent infection, but the protection afforded varies by population; uptake is also limited in some groups. Antiviral drugs for influenza are now readily available. Oseltamivir is the most widely used antiviral for the treatment and prophylaxis of seasonal influenza, and its efficacy and safety are now well established in a variety of populations. In addition to decreasing the severity and duration of the symptoms of influenza, clinical and epidemiological studies demonstrate that oseltamivir significantly reduces the frequency of secondary illnesses and exacerbation of underlying conditions; survival is also significantly improved in seriously ill patients who are hospitalized with severe influenza. Resistant viruses are isolated with a low frequency during oseltamivir treatment (0.33% in adults and 4.0% in children among almost 2000 oseltamivir-treated patients enrolled onto Roche-sponsored clinical trials of oseltamivir treatment during the oseltamivir development programme). However, an oseltamivir-resistant influenza A (H1N1) virus emerged in Europe during the 2007-08 season and circulated in the southern and northern hemispheres in 2008-09. No link with oseltamivir usage could be detected, and the clinical impact of these viruses was limited. Oseltamivir-susceptible pandemic (H1N1) 2009 viruses now predominate in many countries. Oseltamivir is generally well tolerated, with a similar adverse event profile to placebo.

Figure 1

Incidence of laboratory-confirmed influenza infection in household contacts without influenza at baseline who did or did not receive oseltamivir post-exposure prophylaxis (commenced within 48 h of symptom onset). Figure derived from data in Hayden et al.

Figure 2

Incidence of laboratory-confirmed clinical influenza in elderly nursing home residents who received 6 weeks of seasonal prophylaxis with oseltamivir or placebo. Figure derived from data in Peters et al.

Figure 3

Total influenza A viruses subtyped as H1N1 (n = 5984), and number of oseltamivir-resistant and oseltamivir-susceptible H1N1 viruses for which oseltamivir susceptibility was determined (n = 2949), by week, Europe, winter 2007–08. Reproduced from Meijer et al. with permission.

Figure 4

(a) Mean (±SD) concentration–time profile for oseltamivir in plasma after a single oral dose of 150 mg of oseltamivir phosphate in Caucasian (n = 4) and Japanese (n = 4) subjects and the overall population (n = 8). (b) Mean (±SD) concentration–time profile for oseltamivir in CSF after a single oral dose of 150 mg of oseltamivir phosphate in Caucasian (n = 4) and Japanese (n = 4) subjects and the overall population (n = 8). Reproduced from Jhee et al. with permission.

Figure 5

(a) Mean (±SD) concentration–time profile for oseltamivir carboxylate in plasma after a single oral dose of 150 mg of oseltamivir phosphate in Caucasian (n = 4) and Japanese (n = 4) subjects and the overall population (n = 8). (b) Mean (±SD) concentration–time profile for oseltamivir carboxylate in CSF after a single oral dose of 150 mg of oseltamivir phosphate in Caucasian (n = 4) and Japanese (n = 4) subjects and the overall population (n = 8). Reproduced from Jhee et al. with permission.