Neuraminidase inhibitors: Zanamivir and oseltamivir

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of zanamivir and oseltamivir for the prophylaxis and treatment of influenza. DATA SOURCES: A MEDLINE search restricted to English-language journals was conducted (1980-May 2000). STUDY SELECTION AND DATA EXTRACTION: All efficacy and safely trials were included if conducted in humans and published in a journal. Abstracts were included if no other data source was available. DATA SYNTHESIS: Zanamivir and oseltamivir block influenza neuraminidase and prevent the cleavage of sialic acid residues, thus interfering with progeny virus dispersement within the mucosal secretions and reducing viral infectivity. The neuraminidase trials for prophylaxis and treatment of influenza enrolled predominantly young (mean age 29-37 y); healthy, mostly unvaccinated individuals who were at the lowest risk of influenza and its complications. When zanamivir 10 mg inhaled twice daily or oseltamivir 75 mg orally twice daily were used for treatment, systemic symptoms such as myalgias, fever, and headache were reduced by approximately 0.7-1.5 days. Greater efficacy (symptom reduction by 1.5-2.0 d) was noted in proven cases of influenza infection, in febrile patients, and in patients who received the treatment medication within 30 hours of symptom onset. Clinical efficacy did not increase when doses higher than the treatment dose approved by the Food and Drug Administration were used. When zanamivir 10 mg inhaled once daily or oseltamivir 75 mg orally once daily was used:for four to six Weeks and achieved protective clinical efficacy for laboratory-confirmed influenza ranging from 67% to 74%, depending on whether culture or serologic tests were performed. The most common adverse effects (usually <5%) included upper respiratory tract symptoms. Patients with asthma or chronic obstructive pulmonary disease who received zanamivir had an increased incidence of a >20% decline in forced expiratory volume in one second or peak expiratory flow rates. Headaches, nausea, and vomiting were more frequent in the oseltamivir groups than in placebo groups. The most common gastrointestinal adverse effects, nausea and vomiting, were reduced to approximately 10% by administering the medication with food. CONCLUSIONS: Zanamivir and oseltamivir are more effective in preventing culture-positive influenza in febrile (greater than or equal to 37.8 degreesC) individuals. Treatment is more effective if initiated within 30 hours of symptom onset in febrile individuals; however, it is difficult to meet these criteria. More realistically clinical efficacy is closer to 60-70% and for treatment started within 48 hours for laboratory-confirmed influenza, symptom reduction is approximately 0.7-1.5 days. If used appropriately to minimize the development of resistance, the neuraminidase inhibitors represent a new and unique class of antiinfluenza agents i that can potentially reduce the morbidity associated with influenza.