Oseltamivir - A review of its use in influenza

Oseltamivir is a prodrug of oseltamivir carboxylate (Ro 64-0802, GS4071), a potent and selective inhibitor of the neuraminidase glycoprotein essential for replication of influenza A and B viruses, Studies in volunteers with e xperimental human influenza A or B showed that administration of oral oselt amivir 20 to 200mg twice daily for 5 days reduced both the quantity and dur ation of viral shedding compared with placebo. Subsequent assessment of the drug at a dosage of 75mg twice daily for 5 days in otherwise healthy adult s with naturally acquired febrile influenza showed that oseltamivir reduced the duration of the disease by up to 1.5 days and the severity of illness by up to 38% compared with placebo when initiated within 36 hours of sympto m onset (earlier initiation of therapy was associated with faster resolutio n). The incidence of secondary complications and the use of antibacterials were also reduced significantly in oseltamivir recipients, A liquid formula tion of oseltamivir (2 mg/kg twice daily for 5 days) has been shown to be e ffective in the treatment of children with influenza, and data presented in abstracts suggest that the drug may also be of use in high-risk population s such as the elderly or those with chronic cardiac or respiratory disease, In addition to treatment efficacy, the drug has demonstrated efficacy when used for seasonal or household prophylaxis. Oral oseltamivir (75mg once or twice daily for 6 weeks) during a period of local influenza activity signi ficantly prevented the development of naturally acquired influenza by >70% compared with placebo in unvaccinated otherwise healthy adults, The drug al so demonstrated efficacy when used adjunctively in previously vaccinated hi gh-risk elderly patients (92% protective efficacy). Short term administrati on of oseltamivir (75mg once daily for 7 days) may significantly reduce the risk of illness in household contacts of infected persons when administere d within 48 hours of symptom onset in the infected person. Oseltamivir 75mg twice daily for 5 days was well tolerated in clinical trials in healthy ad ults and high-risk patients, with nausea and vomiting being the most common ly reported events. Gastrointestinal events were mild and transient and bot h nausea and vomiting were less likely when oseltamivir was taken with food . Conclusions: Oseltamivir is a well tolerated orally active neuraminidase inhibitor which significantly reduces the duration of symptomatic illness a nd hastens the return to normal levels of activity when initiated promptly in patients with naturally acquired influenza, It therefore represents a us eful therapeutic alternative to zanamivir (especially in patients who prefe r oral administration or who have an underlying respiratory disorder) and t he M-2 inhibitors amantadine and rimantadine (because of its broader spectr um of anti-influenza activity and lower likelihood of resistance) in patien ts with influenza. In addition, although annual vaccination remains the bes t means of influenza prevention, there may be a place for oseltamivir in pr oviding household prophylaxis or adjunctive prophylaxis in high-risk vaccin ated patients during an outbreak of the disease or for use in patients in w hom vaccination is unsuitable or ineffective.