- Medicines and Healthcare products Regulatory Agency
- Therapeutic area:
- Immunology and vaccination and Infectious disease
Outline of the safety experience of these medicines in the UK from our proactive safety monitoring strategy.
Article date: October 2010
On June 11, 2009, WHO declared an official influenza pandemic (phase 6), reflecting global spread of a new strain of human flu H1N1 virus. A UK-wide strategy of offering a flu antiviral (oseltamivir or zanamivir) to everyone with flu-like illness was implemented. In October 2009, a mass immunisation campaign with the novel pandemic H1N1 influenza vaccines Pandemrix and Celvapan commenced across the UK. Vaccine was offered to all front-line health and social-care workers, those at increased risk of flu complications, and healthy children. Although there was already substantial clinical experience with the antivirals, there was no post-licensing experience with the vaccines.
Real-time safety monitoring
We developed a proactive, real-time safety monitoring strategy to meet the challenges of the pandemic. This involved:
- development of a dedicated online portal for reporting suspected adverse reactions to pandemic vaccines and antivirals
- statistical analysis of the number of observed adverse events versus those that would be expected to occur in the absence of receiving a pandemic vaccine or antiviral, to detect new safety signals
- weekly publication of the emerging safety profile
Pandemic vaccine safety profiles
To date, at least 6 million doses of Pandemrix and at least 30 000 doses of Celvapan have been given in the UK. As at June 18, 2010, 3400 and 43 suspected adverse reactions were reported to MHRA in association with Pandemrix and Celvapan, respectively. It is estimated that at least 30 million and 566 000 people have been vaccinated with Pandemrix and Celvapan, respectively, across the EU during the pandemic.
In the UK, use of Celvapan was limited to those for whom Pandemrix was not suitable. On the basis of the few reports received in association with Celvapan, no new safety concerns have emerged in the UK; similarly, no significant safety issues have arisen in the EU (see the influenza update section of the European Medicines Agency website).
During the pandemic, MHRA received 15 suspected reports of Guillain Barré Syndrome (GBS) in temporal association with Pandemrix vaccine; not all cases had the diagnosis confirmed. It was evident from our analyses early in the vaccination programme, including similar analyses across the EU, that there was no clear indication of a large increased risk of GBS similar to that seen with swine flu vaccines in the US in 1976.
To date, there remains no confirmed evidence to indicate that Pandemrix or Celvapan is associated with an increased risk of GBS. However, given the uncertainties in the available information and as with seasonal flu vaccines, a slightly elevated risk of GBS following H1N1 vaccines cannot be completely ruled out. The benefits of vaccination would still outweigh any small vaccine-attributable risk of GBS. Epidemiological studies are ongoing to further assess this possible association.
Febrile seizures in children
Clinical trial data for Pandemrix showed that in children aged from 3 months to 6 years, the second dose (half the adult dose) was associated with greater reactogenicity compared with the first, particularly shown as higher fever rates—likely to increase the risk of febrile convulsion. MHRA received 12 reports of febrile seizures in children, all in the age-group within which febrile convulsions usually occur.
Product information for Pandemrix was amended in December 2009 to warn of the risk of fever, and the possibility of febrile seizures, and to allow for 1 or 2 doses to be given to children. Other than the risk of higher rates of fever after a second dose, there is no indication of any new or specific safety concerns in children.
See this month’s Yellow Card Scheme update for information on the risk of febrile seizures with seasonal vaccination.
Overall, the safety profile of both vaccines was very much as expected, and broadly similar to the established profile for seasonal influenza vaccines. Most suspected adverse reactions were injection site reactions or signs and symptoms of mild ‘flu-like illness’.
Antivirals safety overview
During the pandemic, more than 1 million courses of oseltamivir and more than 14 000 courses of zanamivir were supplied to patients in the UK. During this time, the MHRA received 1100 suspected adverse reactions in association with oseltamivir and 38 in association with zanamivir. The safety profile of oseltamivir and zanamivir in the UK has been broadly in line with the expected profile: no new safety issues have been confirmed for either antiviral during the pandemic.
Article citation: Drug Safety Update October 2010, vol 4 issue 3: H1.