Treatment of Influenza. Dr. YU Wai Cho

Transcription

1 Treatment of Influenza Dr. YU Wai Cho

2 Symptomatic Treatment Analgesics/ Antipyretics (avoid aspirin) Adequate fluids Rest

3 Specific Drug Treatment Synthetic amines Amantadine Rimantadine Neuraminidase inhibitors Zanamivir Oseltamivir

4 The Influenza Virion Neuraminidase M1 Protein Haemagglutinin Single-stranded RNA M2 Protein

5 Amantadine Synthetic, water-soluble amine Experimentally: Inhibit growth of influenza virus in cell cultures Limit influenza virus replication in animal models Protect hamsters from influenza infection by others Mode of action is inhibition of M2 proteins, thus interfering with ion channels for virus replication and re-assembly

6 Replication Cycle of Influenza Virus Attachment Release Amantadine Assembly & Budding Uncoating

7 Amantadine Efficacy Double blind, placebo controlled study 153 subjects with serologically proven influenza A infection [Hong Kong/68(H3N2)] (Amantadine( is not effective against influenza B) No. of subjects Mean duration of fever (hours) Mean duration of symptoms (h) Antibody response profile Placebo Amantadine (p<0.01)( (NS) (Same) Galbraith AW. Lancet 1971; 2(7716):113-5

8 Amantadine Prophylaxis N=450 Placebo Amantadine Rimantadine Dose % ILI % proven influenza Efficacy (%) CNS S/E (%) mg b.d. 6 weeks mg b.d. 6 weeks Not a substitute for vaccine Useful in outbreaks when vaccine is not yet available Dolin R. N Engl J Med 1982; 307(10):580-4

9 CNS Amantadine Side Effects Mild: nervousness, anxiety, light-headedness, headedness, difficulty in concentration Severe (usually seen in overdose: behavioural changes, delirium, agitation, hallucination, seizures GI: Anorexia, nausea, vomiting, constipation Others: Ankle edema, palpitation, urinary retention Development of resistance

10 Rimantadine Resistance Randomised,, placebo controlled study of Rimantadine 100mg b.d.. for 10 days to index patients (with influenza A H3N2) and household contacts Rimantadine conferred no protection to household contacts Rimantadine resistance was found in 8 index patients (28.6%) and 5 contacts, indicating that resistance can be acquired very quickly and can be transmitted from person to person Hayden FG. N Engl J Med 1989; 321:

11 Amantadine - Contraindications Absolute Glaucoma Myasthenia gravis Confusional state Pregnancy, lactation Relative Tendency to hypotension or tachycardia Need dose reduction in renal failure and elderly

12 Amantadine Drug Interactions CNS drugs, especially stimulants Anti-histamines Anti-cholinergics Alcohol

13 Neuraminidase Inhibitor Attachment Neuraminidase Inhibitors Release Uncoating Assembly & Budding

14 Zanamivir Dry powder for inhalation or intranasal application Treatment dosage: 10mg (2 blisters) b.d. for 5 days For patients 5 years or older

15 Zanamivir Must be started within 48 hours of symptom onset Proven efficacy: Reduce duration of illness by 2 days Prophylaxis against influenza infection Reduced need for antibiotic use All known human flu A and flu B Side effect infrequent No significant drug interaction Resistance potential is low

16 Zanamivir and Bronchospasm Some asthmatics were reported to experience bronchospasm after inhaling Zanamivir Recently, a study showed no immediate or severe bronchoconstrictive responses occurred in 5,498 Zanamivir dispensations, and the risk of severe respiratory side effects is very low (Loughlin JE, et al. Clin Ther 2002)

17 Zanamivir & Influenza Compications While some studies report fewer influenza complications following treatment with Zanamivir,, others has reported no difference.

18 Oseltamivir Capsule for oral intake Dosage: 75mg b.d.. for 5 days Children 1-12: 1 12: syrup 2mg/kg/day

19 Oseltamivir Must be started within 48 hours of symptom onset Proven efficacy: Reduce duration of illness by 2 days Reduce complications of influenza by 50% Prophylaxis against influenza infection All known human flu A and flu B GI side effects in up to 9% (but not different from placebo) Dose reduction is needed in moderate renal impairment No significant drug interaction Resistance is < 1% in adults

20 Advantages of Oseltamivir Versus Amantadine Safer Active against both flu A and flu B Versus Zanamivir Oral route Proven to reduce complications of influenza Can be used in young children Systemic nature: potential for treatment of complications

21 Antivirals for ILI Should we prescribe antivirals for every patients with ILI? Should we prescribe antivirals for ILI patients only when there is a positive rapid-flu-test (RFT)?

22 Antivirals for ILI Cost benefit analysis of: Group 1: Zanamivir for all ILI Group 2: Zanamivir for RFT-positive ILI only Group 3: No Zanamivir During flu epidemics, group 1 did best. Group 2 lost because of unsatisfactory sensitivity of RFT and additional cost of the test When there is <39% flu, Group 3 did best Schwarzinger M. Pharmacoeconomics 2003; 21(3):215-24

23 Thank You