Side effects from Pandemrix® from 21 to 27 November 2009

In the period from 21 to 27 November, the Danish Medicines Agency received 150 new side effect reports covering a total of 475 suspected side effects (adverse reactions). Most of the adverse reaction reports are not serious and describe already known adverse reactions. 14 of the reports are classified as serious. The Danish Medicines Agency concludes that the adverse reactions seen so far after vaccination with Pandemrix® correspond to expectations.

The number of adverse reaction reports submitted since 4 November totals 323, covering altogether 1099 adverse reactions.

We also refer to the first weekly list of adverse reactions reported for H1N1 influenza vaccines from the European Medicines Agency (EMEA). See link in the factbox to the right.

The Danish State Serum Institute has dispensed approx. 500,000 vaccine doses. The exact number of persons vaccinated is unknown, but is estimated to involve at least 248,000 individuals.

Who have reported the side effects?
Since 4 November, 79 % of the adverse reaction reports have been submitted by doctors and other healthcare professionals, while 21 % have been submitted by persons that have been vaccinated.

Age distribution
The age distribution is as follows (based only on reports where age was disclosed):

Gender distribution

From 21 to 27 November, 14 reports are classified as serious, the reports involve:

• Three cases where the persons vaccinated immediately after vaccination developed symptoms interpreted as an allergic reaction with discomfort, rash, nausea and possibly blood pressure fall,
• One case of high fever followed by vomiting and rash,
• One case of respiratory arrest 45 minutes after vaccination,
• One case of seizures on the second and third days after vaccination in a patient with known epilepsy,
• One case of fever, diarrhoea and black vomit seven days after vaccination,
• One case of glomerulonephritis (inflammatory condition of the kidney) in a patient with diabetes,
• One case of Guillain-Barré syndrome (paralyses)
• One case of seizures in a newborn, born four days after the mother had been vaccinated,
• One case of vaginal bleeding in a woman in her 22nd week of pregnancy and premature birth of a stillborn baby (reported in two separate reports),
• Two deaths involving patients with known chronic disorders.

In the first four cases, the Danish Medicines Agency evaluates that there is a connection to the vaccination, and the symptoms are known.

The fifth case, respiratory arrest, which occurred in a weakened patient, appears to have been provoked by swallowing down the wrong pipe, according to the information submitted to the Danish Medicines Agency. The reporting doctor assesses that the respiratory arrest was not caused by the vaccine.

The sixth case involved two seizures experienced by a patient with known epilepsy, who nevertheless had not had any seizures for many years. The Danish Medicines Agency assesses that there may be a causal relationship between the concerned seizures and the vaccination of a person who is susceptible to seizures.

In the seventh case, the patient developed fever, diarrhoea and had black vomit, seven days after vaccination. An endoscopic examination of the oesophagus and the stomach showed nothing abnormal. At the same time, the patient received treatment with another medicine known to cause adverse reactions in the form of bleeding in the oesophagus and the gastrointestinal tract. The Danish Medicines Agency assesses that it is most likely that these adverse reactions were caused by this medicine and not the vaccine.

The eighth case involved a patient with known diabetes, who immediately developed symptoms of inflammation of the kidney, which showed in the form of fluid retention by the body and traces of blood and protein in the urine. A tissue sample from the kidney was taken, which confirmed the diagnosis glomerulonephritis. The Danish Medicines Agency awaits further information before a full evaluation can be made.

In the ninth case, the person vaccinated developed paralyses, which, among other things, involved the respiratory muscles. The Danish Medicines Agency awaits further information before a full evaluation can be made.

The tenth case involved the seizures in a newborn baby, four days after the mother had been vaccinated. A CT scan of the brain showed consequences of insufficient blood supply to an area of the brain (medial infarction). The Danish Medicines Agency awaits further information before a full evaluation can be made.

In the 11th and 12th cases, involving respectively, vaginal bleeding in a woman in her 22nd week of pregnancy, and the premature birth of a stillborn baby, the Danish Medicines Agency finds cause to suspect that the outcomes were caused by a pelvic inflammatory disease and a weakened cervix. Vaccination is not suspected to have caused the outcome.

One death occurred in a patient with a known cancer disease that was spreading. Vaccination is NOT suspected to have caused the fatal outcome.

One death occurred in a patient with known HIV infectious disease and a known serious psychiatric disorder. Vaccination is NOT suspected to have caused the fatal outcome.

Categorisation of side effects (adverse reactions)
The total number of adverse reactions breaks down on four categories:

• reactions at the injection site (111),
• allergic reactions (94),
• other known adverse reactions (704 - the adverse reactions appear from the summary of product characteristics of Pandemrix®),
• unknown adverse reactions (191 - the adverse reactions do not appear from the summary of product characteristics of Pandemrix®).

For further details about the individual adverse reactions, please see the factbox to the right.

General information about adverse reaction data
An adverse reaction report contained in the pharmacovigilance database does not necessarily imply that the adverse reaction is associated with the medicine (causality).

• The Danish Medicines Agency registers information about an adverse reaction in the database even if it is only suspected that there might be an association between the medicine and the adverse reaction. Therefore, the information in the database may include real adverse reactions from a medicine as well as random incidences due to e.g. a disease in the patient or another medicine which the patient is receiving at the same time.
• The Danish Medicines Agency is only notified of a small proportion of all adverse reactions. Therefore, the information in the pharmacovigilance database cannot indicate the frequency of the adverse reactions.
• A single adverse reaction report may contain more than one adverse reaction. Therefore, the number of registered adverse reactions is usually higher than the number of adverse reaction reports.
• An adverse reaction is considered to be serious if it results in the patient’s death, is life-threatening, requires hospitalisation, results in significant disability, or if the patient is unable to work or go to school.
• The Danish Medicines Agency sends information about all serious adverse reactions to the marketing authorisation holder, to the European pharmacovigilance database and to the WHO.
• All reports must form part of the periodic safety update reports which the marketing authorisation holder must regularly send to the Danish Medicines Agency. A periodic safety update report describes all reported adverse reactions from all countries in which the medicine is marketed. The periodic safety update reports thus provide a good overview, and they form an important basis for continuous updates of the summary of product characteristics and the package leaflet.
• An unknown adverse reaction is an adverse reaction that today, is not listed in the summary of product characteristics. If it appears that it is a new, as yet unacknowledged adverse reaction, the adverse reaction will be added to the summary of product characteristics.

In connection with the current pandemic, the Danish Medicines Agency discusses the adverse reaction reports at weekly meetings with the Danish National Board of Health and the State Serum Institute.

Both doctors and patients are encouraged to continue reporting adverse reactions to the Danish Medicines Agency.

The next adverse reactions update will be published in the middle of week 50.

For further information, please contact Chief Medical Officer Doris I. Stenver, Consumer Safety Division, tel.: +45 4488 9247 or mobile +45 2246 0979.

Danish Medicines Agency, 3 December 2009