The Role of the Pharmacist in Fourteen National Pandemic Influenza ...

The Role of the Pharmacist in Fourteen National Pandemic Influenza Preparedness Plans in Europe An Analysis

Study carried out by the Europharm Forum Working Group Pandemic Influenza March 2009

EuroPharm Forum Programme: Co-ordinator: Working Group Members 2009:

Pandemic Influenza Florence Petit (FRA) 6 countries: Hélène Leblanc (France); Daniela Schierhorn (Germany); Attila Horváth-Sziklai (Hungary); Pamela Logan (Ireland); Stevce Aceski (The former Yugoslav Republic of Macedonia); Michelle Styles (United Kingdom); Agnes Gombos (Norway).

EuroPharm Forum Secretariat c/o Pharmakon, WHO Collaborating Centre for Drug Policy and Pharmacy Practice Tel.: +45 4820 6000 www.europharmforum.org

The Role of the Pharmacist in Fourteen National Pandemic Influenza Preparedness Plans in Europe An Analysis

Study carried out by the Europharm Forum Working Group Pandemic Influenza March 2009

Table of Contents Executive Summary........................................................................................................3 I) Introduction and Objectives of the Study ................................................................5 II) Methodology .............................................................................................................6 III) Analysis of 14 Plans Available in English and French .......................................................7 III-1) Data from Previous Studies ................................................................................7 1) Results of the study carried out by the London School (April 2006)...............7 2) Report of the European Centre for Disease Prevention and Control (2007) ....8 III-2) Areas of Pharmacist Intervention ........................................................................8 1) Participation of pharmacists in Preparatory Committees ...............................9 2) Prevention and education...........................................................................9 Supporting national health campaigns on basic hygiene measures Preventive material 3) Antiviral medicines...................................................................................10 Preparing the Oseltamivir phosphate solution Oseltamivir capsules Priority groups for antivirals Other medicines mentioned Procedure for dispensing antivirals 4) Vaccination strategy ................................................................................16 Vaccination against seasonal influenza Vaccination against pneumococcus Pandemic vaccine Pre-pandemic vaccine 5) Safety of dispensing sites .........................................................................19 6) New legislative framework for pharmacist intervention to ensure continuity of care.....................................................................................19 7) Home stockpiles ......................................................................................21 IV) Annexes ..................................................................................................................23 IV-1)

International Alert Phases and Plan Situations ...................................................23

IV-2)

Bibliography ....................................................................................................24

IV-3)

Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to the WHO on 10 Sep 2008 ..............................................................27

IV-4)

Background to Clinical Manifestations of Avian Influenza ....................................28

IV-5)

Maps...............................................................................................................29

Executive Summary In the case of an influenza pandemic, whatever the procedures and channels envisaged by national authorities in their preparedness plans, pharmacists will be very much in demand, given their high accessibility. An analysis of 14 national plans allows an overview of the functions which could be assigned to pharmacists. Some of them are obvious, others are more original.

Hygiene recommendations and preventive material/prevention and education Thanks to their accessibility and competency, pharmacists have a key role to play in promoting preventive hygiene measures both to the general public and to people around infected patients. Pharmacists will also have to dispense preventive material such as masks and gloves.

Dispensing antiviral medicines As long as the vaccine is not available, antiviral drugs will be used, both for prophylaxis use and for treatment. Pharmacists will have a key role to play in the rapid mobilisation and the correct use of these medicines. In some countries (Germany, Austria, Spain), pharmacists will prepare the Oseltamivir phosphate solution from powder, in community pharmacies and/or hospital pharmacies. This powder form has the advantage of reducing costs of the treatment compared to that of hard capsules by half and facilitates adaptation for children. In the other countries, the hard capsule form was preferred. In most of the plans, priority groups who will receive antiviral drugs have been determined, because of a particular professional exposure, a specific vulnerability, or the need to maintain essential public services (medical staff, police, etc.). The preventive dispensing of antiviral drugs to priority people should fall under the scope of the competence of pharmacists. However, the procedures to be applied are rarely provided for in the plans. If the virus reaches humans, the first cases will be treated in hospitals, but from phase 6 onwards (pandemic), hospital services will be reserved for severe cases, and care will be provided at community level, including in community pharmacies. The countries adopted different strategies regarding the dispensing of antiviral drugs: via all community pharmacies (France), through selected hospital pharmacies (Malta), or by parallel distribution channels (United Kingdom). These parallel channels raise the question of access to other medicines for the patients who are dispensed antiviral drugs through these channels. Whatever the distribution channels, security could be an issue, as the national stockpiles will not be sufficient to treat the whole population. This issue is not generally mentioned except in the United Kingdom and in Malta, where the presence of security staff at the dispensing points is envisaged. Besides antiviral drugs, further medicines will be required to treat associated pathologies such as bacterial pneumonia: antibiotics, antimicrobials, etc. Few plans (Germany, Greece, Austria, and Switzerland) tackle this problem. Stock shortages might occur if these needs are not properly anticipated.

The Role of the Pharmacist in Fourteen National Pandemic Influenza Preparedness Plans in Europe; Analysis

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Further exceptional measures are envisaged in Malta, i.e. 24 x 7 hour emergency pharmacies and a supply of essential medicines via the postal system.

Vaccination strategy There is evidence that vaccinating high-risk groups against seasonal influenza will encourage an increase in the immune response to the H5N1 virus. It is also a means to increase the vaccine production capacity in case a pandemic occurs. That is why the WHO encourages national authorities to vaccinate 75 % of people in high-risk groups. Many European countries implemented a strategy of vaccination against seasonal influenza for priority groups. Besides, vaccination of risk groups against pneumococcus is recommended in several countries (e.g. Belgium, Estonia, Greece) to decrease the frequency of pneumococcal pneumonia, which turns out to be a major cause of death in the case of influenza pandemics. As far as the pandemic vaccine is concerned, the difficulty is that it is only possible to develop it for a specific virus once it emerges. It is likely to be at least six months after the pandemic is declared before any significant quantities of a pandemic vaccine become available. Therefore, most plans once again determine priority groups. The distribution of the vaccine is rarely addressed in the plans. This issue needs to be raised. The needs concerning the cold chain should be addressed in advance. As far as vaccine administration is concerned, in the United Kingdom, it is envisaged that pharmacists could have a role to play. It might be interesting for other countries to investigate the feasibility of such a role for pharmacists. Pre-pandemic vaccines have been recently developed by pharmaceutical companies. The Irish and Swiss plans refer to this vaccine. In Ireland, the vaccine currently in the national stockpile is specific to the H5N1 virus that is already in circulation and not to any virus that may mutate to cause an influenza pandemic. The H5N1 vaccine may provide partial protection from a pandemic strain, but this is as yet unconfirmed. In Switzerland, it is planned that a sufficient stock for the whole population in phase 3 will be acquired.

Pharmacovigilance The large-scale use of antivirals and vaccines should be accompanied by the monitoring of side effects. The plans generally provide for increased monitoring of these medicines. Pharmacists can actively participate in pharmacovigilance notification.

Exceptional roles for pharmacists to ensure continuity of care Because a situation of overcrowding both in hospitals and in the private sector is highly likely, several plans (in particular the United Kingdom and Malta) provide that pharmacists will take on exceptional roles, such as repeat dispensing, supply of regular prescription medicines, therapeutic substitution, administration of parenteral medications. Such an enhanced role for pharmacists could be further investigated by other countries in order to fully take advantage of pharmacists’ competences and to better cope with the pandemic. In the Irish plan, at phase 5, a dedicated telephone hotline will provide people with medical advice and support. The aim is to prevent unnecessary attendance at GP surgeries and hospital emergency departments. This is to prevent the spreading of infection and ensure that these services are available for those who require direct clinical care. In most cases, the advice will be to remain at home and rest, take antiviral drugs and put in place some basic measures to limit the spreading to other household members. People will be told where to go to get these antiviral drugs. 4

EuroPharm Forum 2009 Working Group Pandemic Influenza

I) Introduction and Objectives of the Study Globalisation of exchanges obliges governments to pre-define emergency health intervention plans together. Whether it concerns an avian flu epidemic, bioterrorism or natural disasters, means must be mobilised within the framework of pre-determined plans and, when necessary, these plans must be capable of being integrated into actions carried out on a worldwide scale. In these plans, medicines and pharmacists, of course, come into play. In 1993, during the 7th European Meeting of Influenza and its Prevention, held in Berlin, States were called on to ready themselves to face a possible influenza pandemic. The first cases of avian influenza in animals were recorded in China in 1996. A contamination outbreak which occurred in Hong Kong in 1997, on a chicken farm, was the source of 18 cases of human transmission of the H5N1 virus. 6 of these people died. The reappearance of human cases, at the end of December 2003 in Vietnam and in January 2004 in Thailand, shocked international public opinion, which then became aware of the dangers of this epizootic. Governments quickly became mobilised in order to obtain a combat plan by 2005. For its part, the WHO had alerted governments on the absence of a preparation strategy in the event of such a health risk in one of its resolutions, also dating from 2005. In 2005, the publication of WHO recommendations for drafting these plans helped to facilitate their preparation, the targeted objectives being to reduce the spread of the virus, to decrease the number of cases, the number of hospitalisations and the number of deaths, to maintain essential services and to reduce the socio-economic impact that a pandemic would have. Some of the plans published in 2005 were updated and completed in 2007 in light of these recommendations. The world is presently in phase 3: A new influenza virus subtype is causing disease in humans, but is not yet spreading efficiently and sustainably among humans. On 10 September 2008, the WHO reported 387 cases of human contamination in the world since the first case of human contamination recorded in 2003. 287 of these people had died. These deaths concerned 15 countries in Africa, Asia and Europe. Out of 36 human cases recorded in 2008, 25 deaths have been reported in Indonesia, Egypt, China and Vietnam. Bangladesh was the only new country to report human cases in the first half of 2008. The death rate in 2008 was at 76 % as opposed to 63 % overall since 2003. In 2008, the highly pathogenic avian influenza virus is still present in Asia. The disease has become “enzootic” in Indonesia, and outbreaks reappear regularly in Pakistan, in Bangladesh, India, Laos, Thailand, Vietnam and in the Republic of Korea. In Egypt, the infection is endemic, whereas, in Europe, it remains limited to isolated cases affecting wild or farm birds. The objective of the current study is to list all the measures envisaged in the governmental plans preparing for an influenza pandemic that will mobilise pharmacists either in a direct or indirect manner, whether it concerns actions of medicinal prevention or not and distribution of medicines or protective material.


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II) Methodology This study was carried out in the first half of 2008. It is based on the bibliographic analysis of 14 governmental plans available in English or French. The data collected have been completed by elements received by members of the EuroPharm Forum Working Group Pandemic Influenza. Analysis of the plans mainly focused on all items that could concern pharmacists, i.e.: behavioural preventive measures (hygiene) protective material prophylactic treatment (antivirals, vaccines) treatment available (antivirals, antibiotics, etc.) organisational measures affecting pharmacists’ activities new prerogatives accorded exceptionally to pharmacists to ensure the efficiency of the health system. The plans included in the study concern the following countries: 1. 2. 3. 4. 5.

Austria, Influenza Pandemic Plan, Strategy for Austria (2006) Belgium, Preparedness Plan Influenza Pandemic, part 2 operational plan (July 2006) Czech Republic, Pandemic Plan of the Czech Republic (October 2006) Estonia, Influenza Pandemic Preparedness Plan, November 2005 France, National Plan for the prevention and control – “Influenza Pandemic” (January 2007) 6. Germany, (July 2005) 7. Greece, National Influenza Pandemic Plan (October 2005) 8. Ireland, National Pandemic Influenza Plan (January 2007) 9. Italy, National Plan for preparedness and response to an influenza pandemic (2006) 10. Malta, Public Health Action, Plan on Avian Influenza in Malta, May 2008 – Malta, Pandemic Influenza Response Plan (July 2007) 11. Slovak Republic, Detailed Plan of Measures in Case of an Influenza Pandemic in The Slovak Republic (November 2005) 12. Spain, National Pandemic Influenza Preparedness and Response Plan Update (December 2006) 13. Switzerland, Swiss Influenza Pandemic Plan (November 2007) 14. United Kingdom, Pandemic Flu, UK influenza pandemic contingency plan (October 2005). The analysis carried out was put into perspective with the available bibliographic elements of plan comparison.

Limitations of the report This report does not claim to be exhaustive. Other documents might have been issued at national level without being referred to. For each of the points tackled, examples of countries where this issue is addressed are given for information only. We only used the version available from the Internet in the first half of the year 2008: 4 of them dated from 2007, 5 from 2006 and 5 from 2005. Therefore, information included in other national documents regarding influenza, or in regional plans for federal countries, is not taken into account. Besides, the national plans are continuously evolving. The version used might have been updated since the collection of data for this report.

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III) Analysis of 14 Plans Available in English and French III-1) Data from Previous Studies 1) Results of the study carried out by the London School (April 2006) In April 2006, an analysis of national plans in the European Union (25 member states) and in Bulgaria, Romania, Norway and Switzerland was carried out by the London School of Hygiene & Tropical Medicine. 21 of them published a plan between 1 January 2002 and 30 November 2005. Each plan was analysed according to a checklist based on the World Health Organization checklist. The average completeness score for all surveyed preparedness plans was 54 %. Plans were satisfactory in addressing areas such as surveillance and communication. But there were a number of gaps common to many plans: The target audience is often unclear. The defined purpose of many plans remains obscure. Many plans document only weak links between human and animal surveillance and response systems. Many countries fail to identify appropriate strategies to ensure early containment of the disease in the case where the pandemic originates in their own country. Few countries explain how they will co-operate with other EU countries. Role and responsibilities of different levels of governments are not always clear. Monitoring and testing of regional preparedness plans are missing in most national plans; The planning and prioritisation of laboratory testing capacities during the pandemic phase are not properly addressed by national plans. Plans do not consider adapting surveillance during a pandemic. Whilst considerable attention is focused on national needs and the purchase of antivirals, less attention is placed on their distribution and supply to a defined population. Moreover, many plans fail to distinguish between treatment and prophylaxis, an issue that could have a profound impact on demand. The impact of pandemic influenza on health systems is likely to be considerable. Few plans address how patients will be managed and where they will be treated. Healthcare facilities need plans that are specific regarding clinical management. But they also need guidance on human resource management, patient triage and admission policies. In addressing pandemic influenza, fewer than half of the plans address the maintenance of essential services despite the need for clearly defined roles and responsibilities at all levels, from ministers to local community-based implementers. As regards the domains of interest to pharmacists, this study raises the following issues: Little attention is paid to the distribution and supply of antivirals to target populations, most of the efforts being concentrated on the acquisition of stocks. Many of the plans do not clearly distinguish between treatment and prophylaxis. Few plans specify how and when to obtain vaccines. Few plans specify how patients will be taken charge of and where they will be treated. Limited ability to test resistance to antivirals. The Role of the Pharmacist in Fourteen National Pandemic Influenza Preparedness Plans in Europe; Analysis

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Monitoring of side effects of vaccines and antivirals is only mentioned in two plans. Seven countries touch upon the ability to test samples with fast diagnosis tests. Diverging approaches on the use of masks have been observed. The use of masks by the public is recommended in 11 countries. The type of mask to be used is not always clear. Seven countries recognise that their plans lack proof of effectiveness. Instructions for use are often lacking. Only some of the plans have touched upon ethical issues (eg Switzerland): Ethical issues linked to the rights and duties of health professionals do not feature in the plans. Ethical issues in relation to the prioritisation of medical interventions and the allocation of vaccines and antivirals are barely touched upon. 2) Report of the European Centre for Disease Prevention and Control (2007) In September 2007, the European Centre for Disease Prevention and Control (ECDC) published an assessment of the state of preparation for an influenza pandemic in the EU. This report is the result of an assessment, led by the ECDC, of national plans to fight avian influenza. The analysis was further deepened by encounters with representatives from each country. This report identifies a certain number of shortcomings in the national plans on the following points: Ability to take vaccination measures for the main risk group: the elderly. The existence of national contingency plans allowing to maintain essential public services such as electricity and food distribution in the case of a pandemic. Work in conjunction with neighbouring countries. Carrying out of exercises at national level in the health sector. For Federal States, co-ordination between intersectoral and sub-national mechanisms of assessment concerning the state of preparation. Development of the national strategy in an intersectoral perspective. Communication tools ready for use in the case of a pandemic. Co-ordination of strategies for human and animal health. The report also identifies five areas on which the States should now focus their efforts: 1. Improving efforts in the area of prevention. 2. Developing integrated plans allowing to maintain efficient public services in the case of a pandemic (transport, police, etc.). 3. Ensuring that the national plans are operational at local level. 4. Developing interoperability of plans at European level (through the Health Security Committee that assists the Council of Ministers, or through common exercises between border countries and at European level). 5. Carrying out less theoretical and more operational research.

III-2) Areas of Pharmacist Intervention According to the WHO recommendation, most of the plans include planning and co-ordination, situation monitoring and assessment, prevention and containment, health system response (antiviral drugs, pandemic vaccine, etc.), and communications. Their aims are to reduce mortality (number of deaths), morbidity (sickness) and to minimise the disruption to society.

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Analysis of the importance given to pharmacists in 14 governmental plans preparing for a possible avian influenza pandemic has allowed us to identify the measures that would have a direct or indirect impact on pharmacists’ activities. 1) Participation of pharmacists in Preparatory Committees Pharmacists’ organisations are rarely mentioned in the committee in charge of defining the strategy, except for the Austrian plan, which mentions that the Austrian Chamber of Pharmacists will be represented within the expanded crisis committee. 2) Prevention and education Supporting national health campaigns on basic hygiene measures The pharmacy is considered a reliable and particularly accessible health centre by the public. The pharmacist is generally the first health professional that patients refer to for health information. Community pharmacists have a key role to provide information, advice and support to people with questions about influenza. They can promote health messages such as common preventive hygienic measures (hand washing, intensive room aeration, use of disposable tissues, avoiding the shaking of hands and touching of eyes, mouth, nose and mucous membranes, etc.). The pharmacy can also support the public in preparing for an influenza pandemic. Another important aspect is hygiene recommendations for people around infected patients. To avoid a spreading of the epidemic, home care requires teaching people around the patient how to strictly implement hygiene recommendations: isolation of the infected person appropriate use of masks protected elimination of infected waste disinfection processes avoiding visits as much as possible. Oral advice will be complemented by information leaflets. For instance, in England, local heath authorities will work with community pharmacies to decide how best to use their services to promote good hygiene practices and support national communications on pandemic influenza preparedness prior to a pandemic. They will consider opportunities to encourage the public to keep basic supplies of medicines in their cupboards and ensure that they are rotated to stay in date. Preventive material

Masks

Flu is an airborne infectious disease, and people can be infected by droplets in the air. The main, personal, preventive equipment is a face mask. It is designed to help reduce exposure to airborne particles. FFP Type masks are also known as individual respiratory protection devices. FFP means Filter Face Piece, and level 2 or 3 indicates the protection given. They are designed to protect the wearer in close contact with patients or their biological samples. Two types of mask are recommended in the plans: respiratory protection masks and surgical or anti-projection masks: 95 % of particles larger than 0.6 micrometres are filtered with FFP2 masks and 99 % are filtered with FFP3 masks. They are quite uncomfortable and are not advised for the


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general population. They are recommended for exposed professionals. Under normal protection, FFP2 and FFP3 type masks could be used to last 8 hours maximum. Anti-projection masks known as surgical masks (FFP1) are recommended for people suffering from the flu to prevent biological particles from being expelled by the wearer into the environment. It protects the people around them. Anti-projection masks could also be worn by unaffected people as a precautionary measure in public places. The types of masks recommended for professionals vary according to the plans: In many of the plans, FFP2-type masks are reserved for exposed personnel, and surgical masks (anti-projection) are recommended for patients. Some plans provide for more sophisticated material: For example, in Austria, protective Type FFP3 masks with exhalation valves are recommended for healthcare workers in direct contact with influenza patients, and FFP3 masks without exhalation valves are recommended for patients. FFP1 or surgical masks are recommended for others. States often have pre-prepared stockpiles of masks. The plans rarely provide for stockpiling by the population itself. This is the case in Switzerland where, since May 2007, the population has been encouraged to create a stockpile of 50 masks per person (except for children).

Gloves

The issue of gloves is touched upon very little in the plans. On this point, the Belgian plan specifies that it does not provide any recommendation for the use of gloves in order to avoid giving a false sense of safety that could lead people to neglecting washing their hands.

Products for hand hygiene

The products recommended for hand hygiene are mainly soap and alcohol-based solutions. The Belgian plan, for its part, envisages a large-scale distribution of alcohol-based solution for disinfection of hands to the entire population. 3) Antiviral medicines Antiviral medicines are the only influenza-specific treatment available that could be used to minimise morbidity and mortality when a vaccine is not yet available. They could be used both for prophylactic use as well as for treatment. These medicines should enable most people to stay at home and care for themselves. Four antivirals exist: Oseltamivir (Tamiflu®), neuraminidase inhibitors (suspension and hard capsule) Zanamivir (Relenza®), neuraminidase inhibitors (powder for inhalation) Amantadine, M2 inhibitors Rimantadine, M2 inhibitors.

Neuraminidase inhibitors are specifically effective drugs against influenza A and B. They should be taken within the first 48 hours after the appearance of the first symptoms to be effective in reducing the intensity and duration of the symptoms (optimally within the first 12 hours). When these drugs are used prophylactically, it could prevent infection in more than 70 % of cases. The use of Tamiflu® for prophylaxis is indicated for a treatment duration of 6 weeks. Oseltamivir is preferable for use in the case of a pandemic as it is administered orally. Its main side effect is gastrointestinal disorders (nausea, vomiting). 10


For older patients, or in case of asthma patients or patients with a respiratory disease, Zanamivir should not be used, as it can lead to an acute bronchospasm. Laboratory tests have shown that the emergence of drug-resistant strains is less likely during treatment with neuraminidase inhibitors (Oseltamivir and Zanamivir) than with M2 inhibitors (Amantadine and Rimantadine). Neuraminidase inhibitors may also have a lower incidence of severe side effects. Most influenza A (H5N1) viruses currently in circulation in Southeast Asia are resistant to the M2 ion channel inhibitors (Amantadine and Rimantadine), and strains that may evolve from these viruses may also become resistant to this class of antivirals. Inhibits

Acts on

Administration

Common Side Effects

Influenza A

Oral

Insomnia, dizziness, gastro-intestinal trouble

M2 ion channel

Influenza A

Oral

Insomnia, gastro-intestinal trouble, (less often than Amantadine)

Oseltamivir

Neuraminidase

Influenza A and B

Oral

Gastro-intestinal

Zanamivir

Neuraminidase

Influenza A and B

Inhaler

Bronchospasm

Amantadine M2 ion channel (tablets, syrup) Rimantadine

None of the available influenza antivirals are approved for use among children aged