Pandemrix

Constituents

As well as the active antigen derived from A/California/7/2009 (H1N1), the vaccine contains an immunologic adjuvant 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.

Use of adjuvant

While other 2009 H1N1 vaccines have been developed, the use of a proprietary immunologic adjuvant 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."

Dosage

The vaccine is supplied in separate vials, one containing the adjuvant, 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.

Availability

As of 3 December 2009, 11.2 million doses of Pandemrix had been delivered to health services in the UK, where the vaccine forms the bulk of the government's mass vaccination programme.

Clinical trials

The EMEA reported results from some clinical trials in the CHMP Assessment Report. These relate to vaccination against H5N1 (Bird Flu) and not H1N1 (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

GlaxoSmithKline 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 muscles, joint pain

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 urticaria (hives)

Rare (affects at least 1 in 10,000):

Serious generalised allergic reactions of anaphylaxis

Fits

Severe stabbing or throbbing pain along one or more nerves

Low blood platelet count which can result in bleeding or bruising

Very Rare (affects less than 1 in 10,000 people):

Vasculitis

Neurological disorders such as encephalomyelitis, neuritis or Guillain–Barré syndrome temporary paralysis

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

In the summer of 2010 the Swedish Medical Products Agency (MPA) and the Finnish National Institute for Health and Welfare (THL) received reports from Swedish and Finnish healthcare professionals that narcolepsy was a suspected adverse drug reaction to the Pandemrix flu vaccination. These reports concern children, aged 12–16 years, whose symptoms occurred one to two months after vaccination. Following thorough medical investigation these symptoms have been confirmed as being compatible with narcolepsy. Consumer reports, describing similar symptoms, have also been received. Both organizations, in consultation with external experts, have begun 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 enquire whether there have been any similar reports in other countries.

Currently, THL is recommending that further Pandemrix vaccinations be discontinued pending further investigation into 15 cases of recently vaccinated children who developed narcolepsy in late 2009 and early 2010. Recently, THL raised this figure to 17; the expected average annual occurrence is six cases. In Sweden, MPA has discovered 12 confirmed cases and another 12 suspected ones. 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."

In February 2011 THL concluded that there is a clear connection between the Pandemrix vaccination campaign of 2009 and 2010 and the narcolepsy epidemic in Finland. The probability of developing narcolepsy was determined to be nine times higher in those who received the Pandemrix vaccination than those who didn't. A total of 152 cases of narcolepsy have been found in Finland during 2009–2010, and 90% of these children had received the 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 the incidence of narcolepsy in relation to upper airway infection 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 adjuvants designed to provoke a stronger immune response. These were not in the vaccine used in China.

In 2013, the New Scientist reported that "part of a surface protein on the pandemic virus looks very similar to part of a brain protein that helps keep people awake". However, the original scientific article claiming that HA protein in both the virus and the vaccine could, in some people, trigger an immune reaction against hypocretin, was recently retracted because the data could not be reproduced. However, further investigations indicated that "antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2".

In 2014, a Finnish group published results that showed Pandemrix contained a higher amounts of structurally altered viral nucleoproteins than Arepanrix, a similar vaccine not associated with narcolepsy.

In 2015 it was reported that the British Department of Health was paying for Sodium oxybate medication for 80 patients who are taking legal action over problems linked to the use of the swine flu vaccine, at a cost to the government of £12,000 per patient per year. Sodium oxybate is not available to patients with narcolepsy through the National Health Service.