Avian Influenza Medication

Updated: Nov 17, 2015
  • Author: Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP; Chief Editor: Michael Stuart Bronze, MD  more...
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Medication

Medication Summary

Current WHO and CDC guidelines (2015) recommend therapy regimens with a neuraminidase inhibitor, preferably oseltamivir. Studies are ongoing as to the relative effectiveness of high-dose and/or prolonged courses of therapy with oseltamivir. [9] If high-dose regimens prove to be more effective, the availability of antiviral medication in the event of a massive outbreak, as well as treatment considerations for mildly versus severely ill people, would be affected.

Although most H5N1 influenza cases are resistant to amantadine or rimantadine (reflecting mutations in the M2 gene segment), combination therapy is recommended unless the patient was exposed in an area known to contain virus strains resistant to the other antiviral agents. Treatment failures due to resistance to single-drug oseltamivir regimens have been reported. [9]

Zanamivir has not yet been tested in people with H5N1 disease, but animal studies are promising and the resistance mutations to oseltamivir do not cause cross-resistance. Some researchers have recommended dual therapy with both existing neuraminidase inhibitors. One concern is that inhaled zanamivir is unlikely to reach distal airways in severe disease. [9]

Two experimental drugs exist; arbidol is available in China and Russia, and peramivir is still being studied. Neither is yet available in the United States.

Currently, the CDC is recommending against using the M2 ion-channel blockers amantadine and rimantadine for routine influenza treatment or prophylaxis because of increasing resistance rates (up to 14.5% in the first half of the 2007-2008 flu season). This advice is subject to change. [12]

Probenecid, a uricosuric, approximately doubles the effective dose of oseltamivir by disrupting renal excretion of the drug and may have a role in a pandemic or in severe infections. [13] No studies have yet been performed to confirm the appropriate dosing regimen in this situation.

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Antivirals, Influenza

Class Summary

Agents that inhibit neuraminidase activity may be of benefit.

Amantadine

Active against influenza A virus. Has little or no activity against influenza B virus isolates.Mechanism of antiviral action is unclear. Prevents release of infectious viral nucleic acid into the host cell by interfering with the function of the transmembrane domain of the viral M2 protein. In certain cases, known to prevent virus assembly during virus replication.Treatment begun within 48 h after the onset of symptoms decreases duration of fever and other symptoms.Indicated for both prophylaxis and short-term treatment. Resistant virus strains may develop and be transmitted.Not recommended by the CDC for the 2005-2006 influenza season because of resistance. Laboratory testing by the CDC on the predominant strain of influenza (H3N2) currently circulating in the United States shows that it is resistant to these drugs.

Rimantadine (Flumadine)

Inhibits viral replication of influenza A virus H1N1, H2N2, and H3N2. Prevents penetration of the virus into the host by inhibiting uncoating of influenza A. Resistant virus strains may develop and be transmitted.Not recommended by the CDC for the influenza season because of resistance. Laboratory testing by CDC on the predominant strain of influenza (H3N2) currently circulating in the United States shows that it is resistant to these drugs.

Oseltamivir (Tamiflu)

Inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, decreases release of viruses from infected cells and thus viral spread. Effective to treat influenza A or B. Start within 40 h of symptom onset. Available as cap (75 mg, 45 mg, 30 mg) and oral susp.

Zanamivir (Relenza)

Inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. Effective against both influenza A and B. To be inhaled through Diskhaler oral inhalation device. Circular foil discs containing 5-mg blisters of drug are inserted into supplied inhalation device.

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Uricosuric Agents

Class Summary

Agents that inhibit the tubular secretion of the active metabolite of the drug may be used as adjunctive therapy.

Probenecid

Inhibits tubular secretion of the active metabolite of oseltamivir, reducing the clearance by approximately 50%. Systemic exposure to oseltamivir is approximately doubled.The appropriate dosing for combination therapy using probenecid and oseltamivir in the treatment of avian influenza has not been established.

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