http://www.tga.gov.au/alerts/medicines/atagi-tga-report.htm
Analysis of febrile convulsions following immunisation in
children following monovalent pandemic H1N1 vaccine (Panvax®/Panvax Junior®, CSL)
Print version of this report (pdf,99kb)
Australian Technical Advisory Group on Immunisation (ATAGI) and Therapeutic
Goods Administration (TGA) Joint Working Group
28 September 2010
In April 2010, an ATAGI - TGA joint working group was established to provide
advice to the Chief Medical Officer on adverse events following the 2010
trivalent seasonal influenza vaccine (TIV). In September 2010, this group was
reconvened to re-examine the rate of febrile convulsions following
administration of the monovalent pandemic H1N1 influenza vaccine, Panvax/Panvax
Junior (CSL) in young children, and in particular, to address the following
questions:
1.Is the rate of early onset systemic adverse reactions (ie fever, febrile
convulsions) in Panvax/Panvax Jnr recipients aged less than 5 years, and
particularly in those less than 3 years, higher than expected?
2.If the rate of adverse events following immunisation (AEFI) post-Panvax/Panvax
Jnr is higher than expected, is this sufficient to alter the overall
risk/benefit profile of the use of Panvax/Panvax Jnr?
3.If the risk/benefit profile of Panvax/Panvax Jnr is unfavourable, do the
findings alter the recommendations for use of Panvax in this age group and if so
how?
Febrile convulsions in young children are well recognised in the setting of
various viral infections, with rates estimated to be as high as at between 10 to
20% in children hospitalised with influenza.1,2 Febrile convulsions are also a
rare but recognised adverse event following immunisation (AEFI), and have been
reported in influenza vaccine post-marketing data at a rate between 1/10,000 and
1/1000 doses, as well as in association with DTPa, Hib and poliomyelitis
vaccines.
Detailed investigations in Australia from April to July 2010 determined that the
2010 trivalent influenza vaccine Fluvax/Fluvax Junior (CSL) was associated with
febrile convulsions in children < 5 years of age at a rate of 500-700 per
100,000 doses. A report of these investigations is on the TGA website
(http://www.tga.gov.au/alerts/medicines/fluvaccine-report100702.htm).
While data available at that time did not suggest a similarly high rate of
febrile convulsions in Panvax/Panvax Jnr recipients, subsequently the question
of whether Panvax/Panvax Jnr is also associated with a lesser, but still
significant, increased risk of febrile reactions and febrile convulsions arose.
As at 17 September 2010 the TGA had received a total of 48 unique reports of
febrile convulsions in children aged less than 5 years who had received Panvax
or Panvax Jnr. Each of these cases (the numerator) were carefully reviewed to
ensure that a consistent case definition was applied and that the timeframe and
age range of the cases (numerator) used in the analysis were consistent with
those used in determining the number of doses administered (the denominator).
Of the 48 reports, 19 were excluded from the analysis because:
•5 occurred in children aged #8805; 4 years; these were excluded from the rate
calculation because the available denominator data were in children < 4 years of
age;
•6 reports were of febrile convulsions occurring more than 24 hours
post-vaccination; cases occurring more than 24 hours post-vaccination are
considered unlikely to be the result of a reaction to the influenza vaccine;
•6 were considered not to be febrile convulsions on detailed clinical review;
and
•2 cases occurred after 1 June 2010; these were excluded from the rate
calculation because the available denominator data used were based on doses
administered up to and including 31 May 2010.
However among these 29 cases it was also noted that 9 children had received one
or more other vaccines at the same time, and a further 5 had a concurrent
illness or infection that could have given rise to a fever or febrile
convulsion.
While it is not possible to ascertain the precise number of doses of Panvax that
have been administered in children, using data from a number of sources
(Australian Institute for Health and Welfare, Australian Childhood Immunisation
Register, NSW Health, QLD Health, and CSL) this has been estimated at between
168,000 and 270,000.
Using these figures, the overall rate of febrile convulsions post Panvax/Panvax
Jnr is estimated to lie between 7 and 18 per 100,000 doses nationally. However
if the raw figure of 48 cases were utilised (the worst case scenario) the rate
would be 29 per 100,000.
The estimate of between 7 and 18 febrile convulsions per 100,000 vaccine doses
(or even the less plausible 29 per 100,000 doses) remains within the specified
range stated within the Panvax Product Information, which identifies febrile
convulsions as a rare adverse event following immunisation (AEFI) based on
post-marketing surveillance data. Rare side effects are generally regarded as
those that occur at a rate between 1/1,000 and 1/10,000 doses (between
10-100/100,000 doses).
This rate is substantially less (at least 25-fold lower) than the estimated rate
of 700 per 100,000 febrile convulsions seen with Fluvax/Fluvax Junior. It is
considered that this rate is acceptable, in light of the overall benefits
anticipated by vaccination against pandemic H1N1 influenza.
1.Chiu SS, Tse CYC, Lau YL, Peiris M. Influenza A infection is an important
cause of febrile seizures. Pediatrics. 2001;108(4).
2.Newland JG et al. (2007) Neurologic complications in children hospitalized
with influenza: characteristics, incidence, and risk factors. J Pediatr
150:306-310.
11th Oct 2010
TGA gives H1N1 vaccine safety tick
Almost 2000 suspected side-effects have been reported in Australia following
vaccination with the H1N1 influenza vaccine Panvax, although most were minor and
regulators say the vaccine is safe and effective.
At 17 September 2010, the TGA reported there had been 1960 reports since the
national immunisation program with Panvax began on 30 September 2009.
The great majority of reports were for mild and common problems such as
headache, soreness and swelling at the injection site, and gastrointestinal
upset (all listed in the Panvax product information).
Of the suspected side-effects, only 190 related to Panvax Junior, with the
majority of these reports for fever and/or vomiting.
The TGA assessment concluded that Panvax was “a safe, effective vaccine for
prevention of the H1N1 influenza”.
To see the full report, with a table of common side-effects, click here.
Febrile convulsion rate for flu vaccine acceptable
An investigation into the link between febrile convulsions and immunisation with
Panvax/Panvax Junior (CSL) has concluded that the current rate was acceptable in
light of the overall benefits of H1N1 vaccination.
The TGA analysis estimated that between seven and 18 febrile convulsions
occurred per 100,000 doses of these vaccines. This was within the range
specified in their PIs and was much less than the estimated rate of 700 per
100,000 convulsions seen with Fluvax/Fluvax junior.
For the full report, click here.