Professor Ivan Hung slide set on the effectiveness of Oseltamivir for the treatment and prophylaxis of influenza infection in adults and children.

1. Appropriate Use of Oseltamivir in
the Treatment & Prophylaxis for
Influenza
Dr Ivan Hung
MBChB (Bristol) MD (HK) FRCP (Edin) FHKCP FHKAM (Medicine) PDipID
Clinical Associate Professor
Department of Medicine
The University of Hong Kong

2. When should antivirals be given?
• CDC recommendation
– hospitalized
– severe, complicated, or progressive illness
– at higher risk for influenza complications
• Outbreak setting
http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm

3. Risk factors for severe influenza in host
• Age
– <2 years
– >65 years old
• Chronic underlying illness
– chronic pulmonary disease
– chronic cardiac disease
– metabolic disorders (esp. diabetes mellitus)
– chronic renal disease, chronic hepatic disease, certain neurological
conditions
– Immunosuppression
– Children on chronic aspirin therapy: Reye syndrome
• Pregnancy (third/second trimester/<2 wk postpartum), IgG2 deficiency
• Obesity (delayed or impaired interferon, proinflammatory cytokine/chemokine, NK
cytotoxicity, dendritic/CD8 T cell function in diet-induced obese mice)
• Chronic smoker

4. Classes of Antiviral
Neuraminidase Inhibitor
• Oseltamivir
• Zanamivir
• Peramivir (FDA emergency
use expired June 2010)
• Laninamivir (PIII)
• 98.2% H1 susceptible to
oseltamivir (H275Y); 100%
susceptible to zanamvir
• 100% H3 and flu B susceptibility
Adamantanes
• Amantadine
• Rimantadine
• Almost 100% resistance
Others:
• Viral RNA polymerase inhibitor
(favipiravir T-705)
• Nitazoxanide: block maturation of
viral hemagglutinin

5. Neuraminidase inhibitor
• Oseltamivir, Zanamivir, Peramivir,
Laninamivir
• Inhibits viral neuraminidase
– Neuraminidase is required for the release of
virus particle from the host cell surface
• Resistance increasing

6. 0
1
2
3
4
5
6
7
8
9
10
11
0 1 2 3 4 5 6 7 8 9
Days
after
symptom
onset
viral
load
(log10
copies/ml)
case
control
Days after symptom onset
Number of patients with viral load
checked on the particular day
0 1 2 3 4 5 6 7 8 9
Case (n = 110) 11 49 34 44 38 35 31 25 17 10
Control (n = 23) 6 12 4 9 5 11 11 7 4 3
Kruskal Wallis test: significant decreasing trend of mean viral load at D0–9 in case compared with control (p < 0.001).
Viral load at D5 lower in cases (4.30 log10 vs 5.71 log10 copies/mL, p = 0.025).
Initial VL correlates with symptom score p=0.05;
Time of Rx initiation: 2.1 day post-symptom onset;
Fever resolves 1.4 day earlier with oseltamivir
Li IW, Hung IF et al. Chest. 2010 Apr;137(4):759-68

7. Hsu J et al. Ann Intern Med 2012;156.

8. Hsu J et al. Ann Intern Med 2012;156.

9. Hsu J et al. Ann Intern Med 2012;156.

10. Jefferson T et al. BMJ 2009;339:b1506

11. Jefferson T et al. BMJ 2009;339:b1506

12. Jefferson T et al. BMJ 2009;339:b1506

13. Jefferson T et al. BMJ 2009;339:b1506

14. Jefferson T et al. BMJ 2009;339:b1506

15. Jefferson T et al. BMJ 2014;348

16. Lee N et al. Eur Respir J 2015;45:1642-52

17. Muthuri SG et al. Lancet Res Med 2014; 10.1016
Reduction in mortality risk:
NAI vs. none: OR 0.81; p=0.0024
NAI ≤2 days vs. >2 days: OR 0.48; p<0.0001

18. Dunning J et al. Lancet Infect Dis 2014;14:1259-70

19. Dunning J et al. Lancet Infect Dis 2014;14:1259-70

20. Dunning J et al. Lancet Infect Dis 2014;14:1259-70

21. Kim WY et al. AAC 2011

22. Hung IF et al. Chest 2013;144:464-73

23. Conclusions
• Oseltamivir is effective for treatment &
prophylaxis of influenza infection
• Low resistance rate
• Limited by time of commencement
• Antiviral combination in severe cases