Influenza Treatment (see Influenza Virus, [[Influenza Virus]])
Indications: patients >1 y/o
Clinical Efficacy
Systematic Review and Meta-Analysis of Neuraminidase Inhibitors (Annals Int Med, 2012) [MEDLINE]
In High-Risk Populations, Oral Oseltamivir Decreased Mortality Rate (Odds Ratio: 0.23), Hospitalization (Odds Ratio: 0.75), and Duration of Symptoms (From 45 hrs -> 33 hrs)
Earlier Treatment with Oseltamivir (Within 48 hrs) was Associated with Better Outcomes
Inhaled Zanamavir Decreased Symptom Duration (From 28 hrs -> 23 hrs) and Hospitalization (Odds Ratio: 0.66), But Had More Complications
No Differences Between Oseltamivir and Zanamavir
Oral Amantadine Decreased Mortality and Pneumonia: data from single study only
Cochrane Database Systematic Review of Efficacy of Neuraminidase Inhibitors in Influenza (Cochrane Database Syst Rev, 2014) [MEDLINE]
Time to First Symptom Alleviation
Oseltamavir Decreased the Time to First Alleviation of Symptoms in Adults by 16.8 hrs (Time to First Alleviation of Symptoms Decreased From 7.0 -> 6.3 Days): effect was observed in healthy children, but no effect was observed in asthmatic children
Zanamavir Decreased the Time to First Alleviation of Symptoms in Adults by 0.60 days (Mean Duration of Symptoms Decreased From 6.6 -> 6.0 Days): no effect was observed in children
Hospitalizations
Oseltamavir Had No Effect on Hospitalization Rate in Adults/Children: prophylaxis also had no no effect on hospitalizations
Zanamavir Hospitalization Rate was Not Reported
Serious Influenza Complications
Oseltamavir Did Not Decrease Serious Influenza Complications in Adults/Children: insufficient data to determine effect of oseltamavir prophylaxis on serious complications
Zanamavir Did Not Decrease Serious Influenza Complications in Adults: prophylaxis also had no no effect on serious complications
Pneumonia
Oseltamavir Decreased the Investigator-Reported, Unverified Pneumonia Rate: however, effect was not significant in trials which used more detailed diagnostic form for pneumonia (and no trials reported effect on radiologically-confirmed pneumonia)
Oseltamavir Prophylaxis Had No Effect on Self-Reported, Investigator-Mediated, Unverified Pneumonia Rate in Adults
Zanamavir Had No Effect on Self-Reported or Radiologically-Confirmed Pneumonia
Zanamavir Prophylaxis Decreased the Self-Reported, Investigator-Mediated, Unverified Pneumonia Rate in Adults
Bronchitis/Sinusitis/Otitis Media
Oseltamavir Had No Effect on the Risk of Bronchitis in Adults
Zanamavir Decreased the Risk of Bronchitis in Adults
Neither Oseltamavir/Zanamavir Decreased Rates of Sinusitis/Otitis Media in Adults/Children
Prophylaxis
Oseltamavir/Zanamavir Prophylaxis Decreased the Risk of Symptomatic Influenza
Conclusions
Oseltamavir/Zanamavir Have Small, Non-Specific Effects on Decreasing the Time to Alleviation of Symptoms in Adults, But Not in Asthmatic Children
Oseltamavir/Zanamavir Prophylaxis Decrease the Risk of Symptomatic Influenza
Trials Do Not Settle the Question of Whether Influenza Complications of Influenza (Pneumonia) are Reduced, Because of a Lack of Diagnostic Definitions
The Lower Bioavailability of Zanamivir May Explain its Lower Toxicity, as Compared to Oseltamivir
Study of High-Dose Oseltamivir in Adults Hospitalized with Influenza A and B (Clin Infect Dis, 2013) [MEDLINE]
High-Dose Oseltamivir Demonstrated No Benefit in Influenza A, But Improved the Virologic Response in Influenza B
Influenza Prophylaxis (see Influenza Virus, [[Influenza Virus]])
Indications: patients >13 y/o
Given x 2 wks during epidemic, during which time vaccine will induce antibody response
Given during facility outbreak, to all exposed regardless of vaccination status, until 1 wk after end of outbreak
Pharmacology
Neuraminidase Inhibitor
Activity: Influenza A + B
Metabolism
xxx
Administration
PO:
Dose Adjustment
Hepatic xxx
Renal: xxx
Oseltamivir Resistance
Sporadic Oseltamivir-Resistant 2009 H1N1 Has Been Reported
Oseltamivir Resistance was Associated with the H275Y (Histidine->Tyrosine) Substitution in Neuraminidase in H1N1 During 2007-2008: this strain was spread worldwide, but has not been prominent in later influenza seasons -> nearly all cases are sensitive to zanamavir
Adverse Effects
Gastrointestinal Adverse Effects
Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): occurs in 19% of cases (decreased when taken with food)
Neurologic Adverse Effects
Psychiatric Effects: appear to be dose-related [MEDLINE]
Renal Adverse Effects
Acute Kidney Injury (AKI) (see Acute Kidney Injury, [[Acute Kidney Injury]]): unclear association
References
Antiviral agents for the treatment and chemoprophylaxis of influenza—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60(1):1–24 [MEDLINE]
Antivirals for Treatment of Influenza: A Systematic Review and Meta-analysis of Observational Studies. Ann Intern Med. 2012;156:512-524 [MEDLINE]
A prospective intervention study on higher-dose oseltamivir treatment in adults hospitalized with influenza a and B infections. Clin Infect Dis. 2013 Dec;57(11):1511-9. doi: 10.1093/cid/cit597. Epub 2013 Sep 17 [MEDLINE]
Oseltamivir and inhaled zanamivir as influenza prophylaxis in Thai health workers: a randomized, double-blind, placebo-controlled safety trial over 16 weeks. J Antimicrob Chemother. Mar 2013; 68(3): 697–707. Published online Nov 9, 2012. doi: 10.1093/jac/dks418 [MEDLINE]
Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2014 Apr 10;4:CD008965. doi: 10.1002/14651858.CD008965.pub4.
[MEDLINE]
Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 Influenza Season. MMWR Morb Mortal Wkly Rep. 2015 Aug 7;64(30):818-25 [MEDLINE]