Oseltamivir and inhaled zanamivir as influenza prophylaxis in Thai health workers: a randomized, double-blind, placebo-controlled safety trial over 16 weeks

Abstract

ObjectivesLong-term chemoprophylaxis using neuraminidase inhibitors may be needed during influenza epidemics but safety data are limited to several weeks. We sought to assess the tolerability of oseltamivir and zanamivir as primary prophylaxis over 16 weeks.MethodsWe conducted a parallel group, double blind, 2 (active drug) :1 (placebo) randomized trial of oral oseltamivir/placebo or inhaled zanamivir/placebo over 16 weeks in healthy, Thai hospital professionals at two Bangkok hospitals. The primary endpoint was study withdrawal due to drug-related (possibly, probably, definitely) serious or adverse events (AEs) graded ≥2.ResultsRecruited subjects numbered 129 oseltamivir/65 placebo and 131 zanamivir/65 placebo. A total of 102 grade ≥2 AEs were reported or detected in 69 subjects: 23/129 (17.8%) versus 15/65 (23.1%) (P = 0.26), and 23/131 (17.6%) versus 8/65 (12.3%) (P = 0.28). Intercurrent infections/fevers [26/102 (25.5%)], abnormal biochemistry [25/102 (24.5%)] and gastrointestinal symptoms [18/102 (17.6%)] were the most frequently reported AEs. There were no drug-related study withdrawals. Eight serious AEs were all due to intercurrent illnesses. Laboratory, lung function and ECG parameters were similar between drugs and placebos.ConclusionsOseltamivir and zanamivir were well tolerated in healthy hospital professionals. Both drugs can be recommended for primary influenza prophylaxis for up to 16 weeks.

Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa

“…The rate of reported adverse events among patients using inhaled zanamivir for extended chemoprophylaxis was not different than among those using a placebo inhaler [384]. A study of extended (16 weeks) oral oseltamivir or inhaled zanamivir chemoprophylaxis vs placebo among Thai healthcare personnel reported no significant differences in adverse events and no withdrawals by drug recipients [395].…”

Factors associated with non-persistence to oral and inhaled antiviral therapies for seasonal influenza: a secondary analysis of a double-blind, multicentre, randomised clinical trial

“…19 20 A recent placebo-controlled safety trial of the use of oseltamivir and zanamivir as preventive monotherapies among healthcare workers did not show any difference in drug-related study withdrawals between the treatment and placebo arms. 21 A recent meta-analysis also reported equal withdrawal rates between the oseltamivir and placebo groups. 22 In the present study, the patients who were randomised to the active combination treatment arm were more likely to report side effects than the patients who were allocated to the two placebo-containing arms.…”

Transmission and Control of Respiratory Viral Infections in the Healthcare Setting

“…Oseltamivir which is administered through the oral route has proved to effectively prevent secondary cases of influenza among household contacts if it is given within 48 h of symptoms initiation of the index case. Zanamivir, which is administered by inhalation per mouth, has also proved effective in preventing secondary influenza cases in households and healthcare workers [54,55], but caution is advised, as its efficacy has only been demonstrated in particular circumstances. During a nosocomial outbreak, in high-risk patients and non-vaccinated healthcare workers, antiviral administration should be implemented.…”