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Article #43: Bird Flu: Tamiflu and Relenza for Prevention and Treatment

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According to a recent report on influenza complications in institutionalized older
in the Journal of Virology, "Although adults. Once-daily oseltamivir for seven
vaccination is the ideal way to reduce to 10 days is also effective for
the interspecies spread of influenza post-exposure prophylaxis in household
viruses, the preparation of a new vaccine contacts, including children, and when
takes six months or more. In the interim, ill index cases receive concurrent
antiviral drugs are the only option." treatment.
Antiviral drugs can be used for both Relenza (zanamivir; the second choice for
treatment and prevention of H5N1 bird treatment of bird flu)
flu, but have significant limitations. 1. Prescription antiviral medication
These drugs are expensive, supplies of approved for treatment of seasonal
them are limited, they have to be given influenza by the FDA.
within a short time period to be 2. Mechanism of action: neuraminidase
effective, and resistance either has inhibitor. (It is a potent and specific
already developed or can develop at any inhibitor of the neuraminidase activity
time. Even under optimal circumstances, of influenza A and B viruses. Compared to
none of them are 100 percent effective. oseltamivir, zanamivir is more active
There are four antivirals that are against influenza B but less active
approved by the U.S. Food and Drug against influenza A/N2 neuraminidases of
Administration (FDA) for use against clinical isolates, although the clinical
influenza-two older and inexpensive importance of such differences is
drugs, amantadine and rimantadine, to uncertain. Zanamivir is inhibitory for
which the bird-flu virus has developed certain influenza A neuraminidase
significant resistance-and two newer, variants that are resistant to
more expensive and more effective drugs, oseltamivir.) [Emphasis added.]
Roche's oseltamivir (brand name: 3. Available forms: Not available in
Tamiflu), and GlaxoSmithKline's zanamivir tablet or pill form; available only for
(brand name: Relenza; must be inhaled). oral inhalation with a proprietary
The two new drugs belong to a class of Diskhaler device.
antiviral agents called neuraminidase NOTE: The proprietary inhaler device for
inhibitors. Tamiflu works by blocking the delivering zanamivir is breath-activated
action of a specific enzyme, known as and requires a cooperative, trained
neuraminidase, on the surface of the patient. The use of the Diskhaler device
influenza virus to prevent it from is not reliable in young children, very
spreading and infecting other cells in infirm or elderly persons, or those
the body. cognitively impaired. Although the
Amantadine was once effective against inhaler has been used effectively in
H5N1, but its effectiveness has older adults, over half of hospitalized
diminished drastically because the virus older adults could not correctly use the
has developed resistance against it. device after instruction.
There is some indication, however, that a 4. Effective only if given within 48
combination of Tamiflu and amantadine hours of onset of symptoms.
might be more effective than Tamiflu 5. FDA-approved for treatment for those
alone. Information about Tamiflu and seven years and older.
Relenza is summarized below:  10 mg (two inhalations) twice
Tamiflu (oseltamivir; the first choice daily for five days.
for prevention or treatment of bird flu) 6. Not FDA-approved for prophylaxis
1. Prescription antiviral medication (prevention) of seasonal influenza (but
approved for treatment of seasonal may be effective).
influenza by the Food and Drug 7. Side effects: Inhaled zanamivir is
Administration (FDA). Note that use of generally well tolerated, and the
Tamiflu for treatment or prevention of frequency of complaints is not
avian influenza (bird flu) is an significantly different from those in
"off-label" use of the medication, that placebo [sugar pill] recipients among
is, a use that has not been officially adults and children aged five years and
approved by the FDA. However, Tamiflu is older.
widely recognized as the best available However, post-marketing reports indicate
medication for prevention or treatment of a potential risk for acute bronchospasm,
bird flu, and its use in this situation respiratory arrest, or worsening of COPD
is recommended by the Centers for Disease [chronic obstructive pulmonary disease]
Control (CDC) and the World Health accompanied by pulmonary edema [water in
Organization (WHO). the lungs], after zanamivir inhalation,
2. Mechanism of action: neuraminidase particularly in persons with underlying
inhibitor (active against all nine airway disease [such as asthma]. Apparent
influenza A neuraminidase subtypes declines in respiratory function have
recognized in nature, including recent also been rarely reported in those
pathogenic avian viruses [H5N1, H7N7, without recognized airway disease.
N9N2], as well as a virus containing the Consequently, use in patients with
neuraminidase from the 1918 pandemic underlying airway disease is not
strain). generally recommended in the United
3. Available forms: 75 mg capsules and 12 States, although treatment in at-risk
mg/ml suspension. patients is used in other countries. If
4. Effective only if given within 48 used in patients with obstructive airway
hours of onset of symptoms. disease, zanamivir should be administered
5. FDA-approved for treatment for those cautiously under close observation and
one year and older.a. Dose for treatment with availability of fast-acting
of influenza for those 12 and older: 75 bronchodilators.
mg twice daily for five days.b. Dose for 8. Use in pregnancy: Category C (meaning
treatment of influenza for those under no scientific studies have been done to
twelve: 2 mg/kg up to a maximum of 75 mg prove that it is safe in
twice daily for five days.c. Side effects pregnancy-because of liability, no such
occurring in five percent or more of studies are ever undertaken-but available
patients taking Tamiflu for treatment evidence indicates that it is probably
were nausea, vomiting, and diarrhea. safe to use during pregnancy).
These symptoms generally do not persist 9. Significant drug interactions: none.
with ongoing treatment. Rare instances of How effective is Relenza for prevention
serious side effects have been reported, or treatment of seasonal influenza?
but they are of uncertain relationship to Clinical studies have shown the
Tamiflu. following:
6. FDA-approved for prophylaxis Early inhaled zanamivir (10 mg twice
(prevention) of influenza for those 13 daily for five days) treatment of
and older:a. Dose for prophylaxis of uncomplicated influenza in previously
influenza for those 12 and older: 75 mg healthy adults and children aged five to
daily for 10 days.b. Not approved for 12 years shortens the time to illness
prophylaxis of influenza for those resolution and return to usual activities
younger than 12. However, use of Tamiflu by one to three days. Treatment benefits
in this situation is probably safe and appear to be greater in those with severe
effective. By deduction, dose should be 1 symptoms at entry, in those older than 50
mg/kg up to a maximum of 75 mg daily for years, and in higher-risk patients.
10 days.c. Side effects occurring in five Inhaled zanamivir treatment in adults is
percent or more of patients taking associated with a 40 percent reduction in
Tamiflu for prophylaxis were headache, lower respiratory tract events leading to
nausea, and fatigue. antibiotic use and a 28 percent overall
7. Use in pregnancy: Category C (meaning reduction in antibiotic prescriptions. In
no scientific studies have been done to high-risk patients with primarily
prove that it is safe in mild-to-moderate asthma or other chronic
pregnancy-because of liability, no such cardiopulmonary conditions, zanamivir
studies are ever undertaken-but available treatment reduces illness duration and
evidence indicates that it is probably the incidence of complications leading to
safe to use during pregnancy). antibiotic use.
8. Significant drug interactions: none Prophylactic administration of once-daily
(although probenecid doubles the level of inhaled zanamivir (10 mg) is protective
oseltamivir) against febrile influenza illness during
How effective is Tamiflu for prevention influenza season (84 percent efficacy) or
or treatment of seasonal influenza? when used for post-exposure prophylaxis
Clinical studies have shown the in households with or without treatment
following: of the ill index case (82 percent
Oral oseltamivir is highly protective efficacy).
against experimental human influenza, and One study found that two weeks of inhaled
early treatment is associated with zanamivir was superior to oral
reductions in viral titers, symptoms, rimantadine [another antiviral drug] in
nasal cytokines [inflammatory agents], preventing influenza A infection in
and middle-ear pressure abnormalities. nursing home residents, in part because
Early oseltamivir treatment of acute of a high frequency of rimantadine
influenza in otherwise healthy adults and resistance, and inhaled zanamivir has
children aged one to 12 years reduces the been used to curtail transmission of
time to illness alleviation by one to 1.5 amantadine-resistant influenza A in
days, fever duration, and viral titers in nursing homes. However, inhaled zanamivir
the upper respiratory tract. Early is not approved for chemoprophylaxis
treatment reduces time to functional (prevention) in the United States or most
recovery by three days or more. other countries.
Treatment of children also reduces the Finally, it is important to be aware of
risk for otitis media [inner-ear the fact that the effectiveness of
infection] and decreases overall Tamiflu and Relenza has been studied
antibiotic use. In healthy and high-risk against circulating strains of human
adults, early treatment decreased the influenza, not against the bird flu
risk for lower respiratory tract virus. In a study reported in the August
complications leading to antibiotics and issue of the Journal of Infectious
to hospitalization. In is unknown whether Diseases, Yen and others from St. Jude
treatment reduces the risk for Children's Research Hospital in Memphis,
transmission [of the virus from the Tennessee found that eight-day regimens
infected person to someone else]. of Tamiflu were more effective than the
Prophylactic administration of once-daily suggested five-day regimen for treating
oral oseltamivir (75 mg) is highly infections with the H5N1 bird-flu virus.
effective in reducing the risk for The authors concluded that a prolonged
developing febrile illness during and higher-dose oseltamivir regimen may
influenza season in unimmunized adults. be required for the most beneficial
Prevention of influenza reduces secondary antiviral effect.






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