Pandemrix

Pandemrix
Vaccine description
Target disease Pandemic H1N1/09 virus
Type Killed/Inactivated
Clinical data
Routes of
administration		 Intramuscular injection
ATC code
Legal status
Legal status
Identifiers
ChemSpider
  • none
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Pandemrix is an influenza vaccine for influenza pandemics, such as the H1N1 2009 flu pandemic colloquially called the swine flu. The vaccine was developed by GlaxoSmithKline[1] and patented in September 2006.[2]

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).[3] 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).[3] This vaccine was initially developed as a pandemic mock-up vaccine using an H5N1 strain.[4]

In August 2010, The Swedish Medical Products Agency (MPA) and The Finnish National Institute for Health and Welfare (THL) launched investigations regarding the development of narcolepsy as a possible side effect to Pandemrix flu vaccination in children,[5] and found a minimum 6.6 fold increased risk among children and youths, resulting in a minimum of 3.6 additional cases of narcolepsy per 100,000 vaccinated subjects.[6]

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.[7]

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. [7]

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."[8]

Dosage

The vaccine is supplied in separate vials, one containing the adjuvant, and the other the inactivated virus,[9] 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.[10]

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.[8]

The Marketing Authorisation from the European Medicines Agency expired in August 2015 when GSK Biologicals did not apply for renewal of it citing lack of demand for the vaccine.[11]

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)[12]

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,[13] from the pediatric clinical trial,[14] and the response from the elderly population.[15]

Side effects

GlaxoSmithKline state in their Patient Information Leaflet[16] that the following may occur.

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

Media coverage

The vaccine has received coverage in the business sections of the mainstream UK and International press, including by The Press Association,[17] The British Medical Journal,[18] The Wall Street Journal,[19] and also the Daily Telegraph.[20]

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.[21] 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.[22]

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"[23] reported in Finland and Sweden, so as to "determine whether there is evidence for a causal association".[24]

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." [25]

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.[26][27][28]

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." [29] 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."[30] Since narcolepsy is now believed to be an autoimmune disease [31] 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".[32] 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.[33] However, further investigations indicated that "antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2".[34]

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.[35]

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.[36]

See also

References

  1. ↑ "Pandemic (H1N1) 2009 Influenza Update: GSK's H1N1 'Pandemrix' vaccine receives positive opinion from European Regulators" (Press release). GlaxoSmithKline. 25 September 2009. Archived from the original on 29 September 2009. Retrieved 2009-11-07.
  2. ↑ WO 2006100109
  3. 1 2 "EMEA Pandemrix page". Emea.europa.eu. Retrieved 8 September 2018.
  4. ↑ "Assessment report for the mock-up H5N1 vaccine" (PDF). EMEA. Archived from the original (PDF) on September 2, 2009. Retrieved 2009-11-07.
  5. ↑ "The MPA investigates reports of narcolepsy in patients vaccinated with Pandemrix". The Swedish Medical Products Agency. 2010-08-18. Retrieved 2010-08-19.
  6. ↑ Report from an epidemiological study in Sweden on vaccination with Pandemrix and narcolepsy, Swedish medical product agency, June 30, 2011.
  7. 1 2 Leroux-Roels, Isabel; Bernhard, Roger; Gérard, Pascal; Dramé, Mamadou; Hanon, Emmanuel; Leroux-Roels, Geert (2008). "Broad Clade 2 Cross-Reactive Immunity Induced by an Adjuvanted Clade 1 rH5N1 Pandemic Influenza Vaccine". PLOS ONE. 3 (2): e1665. doi:10.1371/journal.pone.0001665. PMC 2253495. PMID 18301743.
  8. 1 2 Smith, Rebecca (2009-12-03). "Change in swine flu virus is my biggest fear: Liam Donaldson". The Daily Telegraph. London. Retrieved 2010-05-21.
  9. ↑ "Pandemrix packaging information" (PDF). EMEA. Retrieved 2009-11-07.
  10. ↑ Department of Health (UK) (19 October 2009). "Information sheet on the swine flu vaccination" (PDF). p. 8. Retrieved 2009-11-10.
  11. ↑ European Medicines Agency, Public Statement, EMA/656472/2015 "Pandemrix Expiry of the marketing authorisation in the European Union" 19 October 2015
  12. ↑ "CHMP Assessment Report for Pandemrix" (PDF). European Medicines Agency. 24 September 2009. Retrieved 2009-11-07.
  13. ↑ "Pandemic (H1N1) 2009 Influenza Update: Results from second clinical trial of GSK's H1N1 adjuvanted vaccine confirm immune response and tolerability [PAGE NOT EXISTS]" (Press release). GlaxoSmithKline. 16 October 2009. Archived from the original on October 31, 2009. Retrieved 2009-11-07.
  14. ↑ "Pandemic (H1N1) 2009 Influenza Update: Experience of GSK's H1N1 adjuvanted vaccine, Pandemrix, and preliminary paediatric results [PAGE NOT EXISTS]" (Press release). GlaxoSmithKline. 23 October 2009. Archived from the original on October 29, 2009. Retrieved 2009-11-07.
  15. ↑ "Pandemic 2009 Influenza Update: Pandemrix data in an elderly population [PAGE NOT EXISTS]" (Press release). 27 October 2009. Archived from the original on October 29, 2009. Retrieved 2009-11-07.
  16. ↑ "Pandemrix Package Leaflet" (PDF). Who.int. Retrieved 2009-11-07.
  17. ↑
  18. ↑ Stafford, N (2009). "Only 12% of Germans say they will have H1N1 vaccine after row blows up over safety of adjuvants". BMJ. 339: b4335. doi:10.1136/bmj.b4335. PMID 19846501.
  19. ↑ "Today's Stock Market News and Analysis from Nasdaq.com". NASDAQ.com. Retrieved 8 September 2018.
  20. ↑ Smith, Rebecca (2009-09-25). "Swine flu vaccine approved for use". The Daily Telegraph. London. Retrieved 2010-05-21.
  21. ↑ "National Institute for Health and Welfare recommends discontinuation of Pandemrix vaccinations". National Institute of Health and Welfare. 2010-08-25. Retrieved 2010-08-26.
  22. ↑ "Aktuell information om utredningen av fall av narkolepsi efter vaccination med Pandemrix". Medical Products Agency. 2010-08-26. Retrieved 2010-08-26.
  23. ↑ "EU regulator probes swine flu vaccine over narcolepsy fears". PhysOrg. 2010-08-27. Retrieved 2010-08-28.
  24. ↑ Kirby, Jane (2010-08-27). "Swine flu vaccine link to narcolepsy probed". The Independent. London. Retrieved 2010-08-28.
  25. ↑ "Current information on the investigation of cases of narcolepsy after vaccination with Pandemrix - Swedish Medical Products Agency". Lakemedelsverket.se. Retrieved 8 September 2018.
  26. ↑ "THL: Pandemrixilla ja narkolepsialla on selvä yhteys". Mtv3.fi. Retrieved 8 September 2018.
  27. ↑ "Terveyden ja hyvinvoinnin laitos - THL". Terveyden ja hyvinvoinnin laitos. Retrieved 8 September 2018.
  28. ↑ "Narkolepsia ja sikainfluenssarokote - THL". Terveyden ja hyvinvoinnin laitos. Retrieved 8 September 2018.
  29. ↑ "A Swedish registry based cohort study provides strengthened evidence of an association between vaccination with Pandemrix and narcolepsy in children and adolescents - Swedish Medical Products Agency". Lakemedelsverket.se. Retrieved 8 September 2018.
  30. ↑
  31. ↑
  32. ↑ "Flu vaccine helps unravel complex causes of narcolepsy". New Scientist. 2013-12-19. Retrieved 2014-01-03.
  33. ↑ "Journal retracts paper linking vaccine and narcolepsy". Nature News Blog. 2014-07-31. Retrieved 2014-10-07.
  34. ↑ Ahmed, Syed Sohail; Volkmuth, Wayne; Duca, José; Corti, Lorenzo; Pallaoro, Michele; Pezzicoli, Alfredo; Karle, Anette; Rigat, Fabio; Rappuoli, Rino; Narasimhan, Vas; Julkunen, Ilkka; Vuorela, Arja; Vaarala, Outi; Nohynek, Hanna; Pasini, Franco Laghi; Montomoli, Emanuele; Trombetta, Claudia; Adams, Christopher M; Rothbard, Jonathan; Steinman, Lawrence (2015). "Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2". Science Translational Medicine. 7 (294): 294ra105. doi:10.1126/scitranslmed.aab2354. PMID 26136476.
  35. ↑ Vaarala, Outi; Vuorela, Arja; Partinen, Markku; Baumann, Marc; Freitag, Tobias L; Meri, Seppo; Saavalainen, Päivi; Jauhiainen, Matti; Soliymani, Rabah; Kirjavainen, Turkka; Olsen, Päivi; Saarenpää-Heikkilä, Outi; Rouvinen, Juha; Roivainen, Merja; Nohynek, Hanna; Jokinen, Jukka; Julkunen, Ilkka; Kilpi, Terhi (2014). "Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk". PLOS ONE. 9 (12): e114361. doi:10.1371/journal.pone.0114361. PMC 4266499. PMID 25501681.
  36. ↑ "DH funds private prescriptions for drug denied to NHS patients". Health Service Journal. 20 July 2015. Retrieved 20 July 2015.
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