Pandemrix
Encyclopedia
Pandemrix is an influenza vaccine for influenza pandemic
s, such as the H1N1 2009 flu pandemic
colloquially called the swine flu. The vaccine was developed by GlaxoSmithKline
and patented in September 2006.
The vaccine is one of the H1N1 vaccines approved for use by the European Commission
in September 2009 upon the recommendations of the European Medicines Agency
(EMEA). The vaccine is only approved for use when an H1N1 influenza pandemic
has been officially declared by the World Health Organization
(WHO) or European Union
(EU). This vaccine was initially developed as a pandemic mock-up vaccine using an H5N1 strain.
The Swedish Medical Products Agency (MPA) and The Finnish National Institute for Health and Welfare (THL)
have began in Aug 2010 investigations about narcolepsy
as possible side effect to Pandemrix flu vaccination in children, and found at least 6,6 times increased risk among children and youths, or at least 3.6 additional cases of narcolepsy per 100.000 vaccinated subject.
AS03
which consists of DL-α-tocopherol (vitamin E), squalene
and polysorbate 80
.
Thiomersal
(thimerosal) is added as a preservative. Being manufactured in chicken eggs, it contains trace amounts of egg proteins. Additional important non-medicinal ingredients are formaldehyde
, sodium deoxycholate, and sucrose
.
is claimed to boost the potency of the body’s immune response, meaning that only a quarter of the inactivated virus is needed.
Professor David Salisbury, Head of Immunisation at the UK Department of Health
said the vaccines with adjuvants offer good protection even if the virus changes over time; "One of the advantages with adjuvanted vaccines is their ability to protect against drifted (mutated) strains. It opens the door for a whole new strategy in dealing with flu."
, and the other the inactivated virus, which require mixing before intramuscular injection
. Originally it was thought that two doses given 21 days apart would be required for full efficacy.. Subsequent testing has allowed the UK programme to consist of just a single dose for most people, with a two-dose schedule for children under the age of 10 years and immunocompromised adults.
(Bird Flu) and not H1N1
(Swine Flu)
GlaxoSmithKline reported results from the second clinical trial, from the pediatric clinical trial, and the response from the elderly population.
state in their Patient Information Leaflet that the following may occur.
have received in summer 2010 reports from Swedish and Finnish health care professionals regarding narcolepsy
as suspected adverse drug reaction following Pandemrix flu vaccination. The reports concern children aged 12–16 years where symptoms compatible with narcolepsy
, diagnosed after thorough medical investigation, have occurred one to two months after vaccination. Consumer reports describing similar symptoms have also been received. Both organizations have, in consultation with external experts, began to assess the possible relationship between the vaccination and the reported reactions. MPA and THL have been in contact with other EU member states to get information if there are any reports in other countries.
Currently, THL is recommending that further Pandemrix vaccinations are discontinued pending further investigation into 15 cases of recently vaccinated children developing narcolepsy in late 2009 and early 2010. Most recently, THL raised the figure to 17, while the expected average occurrence would be six cases annually. In Sweden, MPA has discovered 12 confirmed and another 12 suspected cases. Additionally, MPA says it is aware of individual case reports from France, Norway and Germany.
On August 27, 2010, the European Medicines Agency
announced that the agency's Committee for Medicinal Products for Human Use
would be launching a review of Pandemrix in light of the "limited number of cases" reported in Finland and Sweden, so as to "determine whether there is evidence for a causal association"
In August 2010 the Swedish MPA issued a statement which included the following: "An investigation is ongoing, but any relationship between the vaccination and the reported symptoms can not be concluded."
THL concluded in February 2011 that there is a clear connection between Pandemrix vaccination campaign of 2009 and 2010 and narcolepsy epidemic in Finland. There was a nine times higher probability to get narcolepsy with vaccination than without it. Total of 52 cases of narcolepsy have been found in Finland during 2009-2010 and 90 % of these children had taken Pandemrix vaccination. Authorities believe that the number of cases may still increase .
At the end of March 2011, an MPA press release stated: "Results from a Swedish registry based cohort study indicate a 4-fold increased risk of narcolepsy in children and adolescents below the age of 20 vaccinated with Pandemrix, compared to children of the same age that were not vaccinated."
The same study found no increased risk in adults who were vaccinated with Pandemrix. While cautioning that the increase in risk for children is still uncertain in magnitude, it recommends they not be vaccinated.
A new study by the Stanford University School of Medicine
examined narcolepsy incidence in relation to upper airway infections and a H1N1 vaccine (not Pandemrix) in Chinese patients. Their principal conclusion was that an increased incidence of narcolepsy was seen following a wave of upper airway infections (such as H1N1 influenza). They found no correlation between vaccination and narcolepsy. According to the authors "The new finding of an association with infection, and not vaccination, is important as it suggests that limiting vaccination because of a fear of narcolepsy could actually increase overall risk."
Since narcolepsy is now believed to be an autoimmune disease
the authors suspect that these upper airway infections trigger an immune response which leads ultimately to narcolepsy in susceptible individuals. Pandemrix contains two adjuvant
s designed to provoke a stronger immune response. These were not in the vaccine used in China.
Influenza pandemic
An influenza pandemic is an epidemic of an influenza virus that spreads on a worldwide scale and infects a large proportion of the human population. In contrast to the regular seasonal epidemics of influenza, these pandemics occur irregularly, with the 1918 Spanish flu the most serious pandemic in...
s, such as the H1N1 2009 flu pandemic
2009 flu pandemic
The 2009 flu pandemic was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus , albeit in a new version...
colloquially called the swine flu. The vaccine was developed by GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
and patented in September 2006.
The vaccine is one of the H1N1 vaccines approved for use by the European Commission
European Commission
The European Commission is the executive body of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union's treaties and the general day-to-day running of the Union....
in September 2009 upon the recommendations of the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
(EMEA). The vaccine is only approved for use when an H1N1 influenza pandemic
Influenza pandemic
An influenza pandemic is an epidemic of an influenza virus that spreads on a worldwide scale and infects a large proportion of the human population. In contrast to the regular seasonal epidemics of influenza, these pandemics occur irregularly, with the 1918 Spanish flu the most serious pandemic in...
has been officially declared by the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) or European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
(EU). This vaccine was initially developed as a pandemic mock-up vaccine using an H5N1 strain.
The Swedish Medical Products Agency (MPA) and The Finnish National Institute for Health and Welfare (THL)
National Institute for Health and Welfare (THL), Finland
The National Institute for Health and Welfare is a Finnish research and development institute operating under the Ministry of Social Affairs and Health. THL was formed on 1 January 2009, with the merger of the National Public Health Institute of Finland and the National Research and Development...
have began in Aug 2010 investigations about narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
as possible side effect to Pandemrix flu vaccination in children, and found at least 6,6 times increased risk among children and youths, or at least 3.6 additional cases of narcolepsy per 100.000 vaccinated subject.
Constituents
As well as a the active antigen derived from A/California/7/2009 (H1N1), the vaccine contains an immunologic adjuvantImmunologic adjuvant
In immunology, an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect in itself. The word “adjuvant” comes from the Latin word adiuvare, meaning to help or aid...
AS03
AS03
AS03 is the trade name for a squalene-based immunologic adjuvant used in various vaccine products by GlaxoSmithKline...
which consists of DL-α-tocopherol (vitamin E), squalene
Squalene
Squalene is a natural organic compound originally obtained for commercial purposes primarily from shark liver oil, though plant sources are used as well, including amaranth seed, rice bran, wheat germ, and olives. All plants and animals produce squalene, including humans...
and polysorbate 80
Polysorbate 80
Polysorbate 80 is a nonionic surfactant and emulsifier derived from polyethoxylated sorbitan and oleic acid, and is often used in foods. Polysorbate 80 is a viscous, water-soluble yellow liquid...
.
Thiomersal
Thiomersal
Thiomersal , and commonly known in the US as thimerosal, is an organomercury compound. This compound is a well established antiseptic and antifungal agent....
(thimerosal) is added as a preservative. Being manufactured in chicken eggs, it contains trace amounts of egg proteins. Additional important non-medicinal ingredients are formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...
, sodium deoxycholate, and sucrose
Sucrose
Sucrose is the organic compound commonly known as table sugar and sometimes called saccharose. A white, odorless, crystalline powder with a sweet taste, it is best known for its role in human nutrition. The molecule is a disaccharide composed of glucose and fructose with the molecular formula...
.
Use of adjuvant
Whilst other 2009 H1N1 vaccines have been developed, the use of a proprietary immunologic adjuvantImmunologic adjuvant
In immunology, an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect in itself. The word “adjuvant” comes from the Latin word adiuvare, meaning to help or aid...
is claimed to boost the potency of the body’s immune response, meaning that only a quarter of the inactivated virus is needed.
Professor David Salisbury, Head of Immunisation at the UK Department of Health
Department of Health (United Kingdom)
The Department of Health is a department of the United Kingdom government with responsibility for government policy for health and social care matters and for the National Health Service in England along with a few elements of the same matters which are not otherwise devolved to the Scottish,...
said the vaccines with adjuvants offer good protection even if the virus changes over time; "One of the advantages with adjuvanted vaccines is their ability to protect against drifted (mutated) strains. It opens the door for a whole new strategy in dealing with flu."
Dosage
The vaccine is supplied in separate vials, one containing the adjuvantAdjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
, and the other the inactivated virus, which require mixing before intramuscular injection
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...
. Originally it was thought that two doses given 21 days apart would be required for full efficacy.. Subsequent testing has allowed the UK programme to consist of just a single dose for most people, with a two-dose schedule for children under the age of 10 years and immunocompromised adults.
Availability
As of 3 December 2009, 11.2 million doses of Pandemrix have been delivered to health services in the UK, where the vaccine forms the bulk of the governments mass vaccination programme.Clinical trials
The EMEA reported results from some clinical trials in the CHMP Assessment Report. These relate to vaccination against H5N1H5N1
Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
(Bird Flu) and not H1N1
H1N1
'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...
(Swine Flu)
- H5N1-007 was initiated at a single site in Belgium (Ghent) in March 2006.
- H5N1-008 was initiated at 41 sites in seven countries (6 EU MS plus Russia) in May 2006.
- H5N1-002 was initiated on 24 March 2007 in four SE Asian countries.
GlaxoSmithKline reported results from the second clinical trial, from the pediatric clinical trial, and the response from the elderly population.
Side effects
GlaxoSmithKlineGlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
state in their Patient Information Leaflet that the following may occur.
- Very common (affects more than 1 in 10 people):
- Headache
- Tiredness
- Pain, redness, swelling or a hard lump at the injection site
- Fever
- Aching musclesMyalgiaMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, joint painArthralgiaArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
- Common (affects at least 1 in 100):
- Warmth, itching or bruising at the injection site
- Increased sweating, shivering, flu-like symptoms
- Swollen glands in the neck, armpit or groin
- Uncommon (affects at least 1 in 1,000):
- Tingling or numbness of the hands or feet
- General constitutional upset of sleepiness or sleeplessness, generally feeling unwell, dizziness.
- Diarrhea, vomiting, stomach pain, feeling sick
- Skin reactions of itching, rash or urticariaUrticariaUrticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
(hives)
- Rare (affects at least 1 in 10,000):
- Serious generalised allergic reactions of anaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
- Fits
- Severe stabbing or throbbing pain along one or more nerves
- Low blood platelet countThrombocytopeniaThrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
which can result in bleeding or bruising
- Serious generalised allergic reactions of anaphylaxis
- Very Rare (affects less than 1 in 10,000 people):
- VasculitisVasculitisVasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
- Neurological disorders such as encephalomyelitisEncephalomyelitisEncephalomyelitis is a general term for inflammation of the brain and spinal cord, describing a number of disorders:* Acute disseminated encephalomyelitis or postinfectious encephalomyelitis, a demyelinating disease of the brain and spinal cord, possibly triggered by vaccination or viral...
, neuritis or Guillain–Barré syndrome temporary paralysis
- Vasculitis
Media coverage
The vaccine has received coverage in the business sections of the mainstream UK and International press, including by The Press Association, The British Medical Journal, The Wall Street Journal, and also the Daily Telegraph.Narcolepsy investigations in the European Union
The Swedish Medical Products Agency (MPA) and The Finnish National Institute for Health and Welfare (THL)National Institute for Health and Welfare (THL), Finland
The National Institute for Health and Welfare is a Finnish research and development institute operating under the Ministry of Social Affairs and Health. THL was formed on 1 January 2009, with the merger of the National Public Health Institute of Finland and the National Research and Development...
have received in summer 2010 reports from Swedish and Finnish health care professionals regarding narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
as suspected adverse drug reaction following Pandemrix flu vaccination. The reports concern children aged 12–16 years where symptoms compatible with narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
, diagnosed after thorough medical investigation, have occurred one to two months after vaccination. Consumer reports describing similar symptoms have also been received. Both organizations have, in consultation with external experts, began to assess the possible relationship between the vaccination and the reported reactions. MPA and THL have been in contact with other EU member states to get information if there are any reports in other countries.
Currently, THL is recommending that further Pandemrix vaccinations are discontinued pending further investigation into 15 cases of recently vaccinated children developing narcolepsy in late 2009 and early 2010. Most recently, THL raised the figure to 17, while the expected average occurrence would be six cases annually. In Sweden, MPA has discovered 12 confirmed and another 12 suspected cases. Additionally, MPA says it is aware of individual case reports from France, Norway and Germany.
On August 27, 2010, the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
announced that the agency's Committee for Medicinal Products for Human Use
Committee for Medicinal Products for Human Use
The Committee for Medicinal Products for Human Use , formerly known as Committee for Proprietary Medicinal Products , is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding medicinal products for human use.E.g.: In June 2007 the CHMP...
would be launching a review of Pandemrix in light of the "limited number of cases" reported in Finland and Sweden, so as to "determine whether there is evidence for a causal association"
In August 2010 the Swedish MPA issued a statement which included the following: "An investigation is ongoing, but any relationship between the vaccination and the reported symptoms can not be concluded."
THL concluded in February 2011 that there is a clear connection between Pandemrix vaccination campaign of 2009 and 2010 and narcolepsy epidemic in Finland. There was a nine times higher probability to get narcolepsy with vaccination than without it. Total of 52 cases of narcolepsy have been found in Finland during 2009-2010 and 90 % of these children had taken Pandemrix vaccination. Authorities believe that the number of cases may still increase .
At the end of March 2011, an MPA press release stated: "Results from a Swedish registry based cohort study indicate a 4-fold increased risk of narcolepsy in children and adolescents below the age of 20 vaccinated with Pandemrix, compared to children of the same age that were not vaccinated."
The same study found no increased risk in adults who were vaccinated with Pandemrix. While cautioning that the increase in risk for children is still uncertain in magnitude, it recommends they not be vaccinated.
A new study by the Stanford University School of Medicine
Stanford University School of Medicine
Stanford University School of Medicine is a leading medical school located at Stanford University Medical Center in Stanford, California. Originally based in San Francisco, California as Cooper Medical College, it is the oldest continuously running medical school in the western United States...
examined narcolepsy incidence in relation to upper airway infections and a H1N1 vaccine (not Pandemrix) in Chinese patients. Their principal conclusion was that an increased incidence of narcolepsy was seen following a wave of upper airway infections (such as H1N1 influenza). They found no correlation between vaccination and narcolepsy. According to the authors "The new finding of an association with infection, and not vaccination, is important as it suggests that limiting vaccination because of a fear of narcolepsy could actually increase overall risk."
Since narcolepsy is now believed to be an autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
the authors suspect that these upper airway infections trigger an immune response which leads ultimately to narcolepsy in susceptible individuals. Pandemrix contains two adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
s designed to provoke a stronger immune response. These were not in the vaccine used in China.
See also
- OseltamivirOseltamivirOseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...
and Zanamivir – antiviral drugs used in the treatment and prophylaxis of influenza - Influenza vaccine
- 2009 flu pandemic vaccine2009 flu pandemic vaccineThe 2009 flu pandemic vaccines are the set of influenza vaccines that have been developed to protect against the pandemic H1N1/09 virus. These vaccines either contain inactivated influenza virus, or weakened live virus that cannot cause influenza. The killed vaccine is injected, while the live...