Reviewer No. 2 checklist for Zanamivir In the WHO

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Reviewer No. 2 checklist for Zanamivir In the WHO Powered By Docstoc
					                           Reviewer No. 2 checklist for:


                      In the WHO Essential Medicines List
(1)     Have all important studies that you are aware of been included? 
              Yes                    No        
(2)     Is there adequate evidence of efficacy for the proposed use? 
                Yes                 No          
(3)     Is there evidence of efficacy in diverse settings and/or populations? 
                Yes                   No         
(4)     Are there adverse effects of concern? 
               Yes                    No        
(5)     Are there special requirements or training needed for safe/effective use? 
               Yes                  No          
(6)     Is this product needed to meet the majority health needs of the population? 
                Yes                 No         
(7)     Is the proposed dosage form registered by a stringent regulatory authority? 
                Yes                 No         

(8)      What action do you propose for the Committee to take? 
         No inclusion as individual medicine in the WHO Essential Medicines List, but rather
as an alternative to oseltamivir (representative of the class of neuramidinase inhibitor,
included with a □ box).

(9)     Additional comment, if any. 
The application is for the inclusion of zanamivir for the prevention and treatment of avian
influenza (H5N1) but most of the information and evidences provided is for influenza A and
B. Some specific information for H5N1 comes from in vitro studies, and animal studies.

If the precautions (no use in children younger than 5 years, not recommended in patients with
underlying airways diseases, such as asthma and COPD, closed monitoring for signs of
abnormal behavior, particularly in pediatric patients) are respected, the safety profile of drug
is acceptable. The drug has been registered for the prevention and treatment of seasonal
influenza by stringent drug regulatory authorities.

The efficacy data presented for the treatment of seasonal influenza shows a limited efficacy in
terms of reduction in the time to alleviation of symptoms, of reduction in the time to return to
normal activities, and in terms of prevention of complications (respiratory tract infections) in
adults and children. Data are not very conclusive for the prevention, but are more convincing
for post exposure prophylaxis.
         From the application:
         “Prophylaxis: Prevention of symptoms
         In summary, compared with placebo, orally inhaled zanamivir appears to be more
         effective than placebo at preventing symptoms of influenza, but not of influenza-like
         Post-exposition prophylaxis
         In summary, compared with placebo, post-exposure prophylaxis with zanamivir
         appeared to be more effective at reducing the duration and number of cases of
         symptomatic influenza and influenza-like illness in households and in individuals.”

Animal studies and in vitro studies give some indications on the possible efficacy against
H5N1 in humans (increased survival rates of animals, decrease of virus titre levels in brain
and lung of animals, in vitro inhibition of viral replication).

The use of treatment in combination with M2 inhibitors like amantadine or rimantadine could
be a possibility to delay the appearance / spread of resistance.

In summary, the data provided for the inclusion of zanamivir for the treatment and prevention
of avian influenza are limited. However, given the pandemic potential of H5N1 if human to
human transmission occurs, the international medical and public health community cannot be
left without any potential tool that could help in the fight against the disease.
As mentioned in the application and in several reference documents, vaccination should be
the first measure implemented, but in the absence of vaccines, zanamivir could be of help.
Even a very partial efficacy of treatment on the duration of symptoms and on complication
such as respiratory tract infections would in case of pandemic change the situation drastically.
Moreover, the potential effect in post exposure prophylaxis could be useful at least at the
beginning of the pandemic.
The WHO guidelines are explicit on the fact that zanamivir should be considered as a second
option, when oseltamivir is not available. Moreover, there are practical difficulties with the
use of zanamivir (cumbersome presentation, diskhaler inhalation device that will need
training for proper use, production and registration in a limited number of countries).

It is therefore suggested to the Committee to not include zanamivir as an individual medicine,
but rather as an alternative to oseltamivir (representative of the class of neuramidinase
inhibitor, included with a □ box).
It should also be recommended that for its use, latest WHO guidelines should be followed,
especially in terms of possible combined treatment.

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