About 5.3 million individuals in Sweden, corresponding to 60% of the Swedish population, have been vaccinated with Pandemrix as of January 8. In total, the Medical Products Agency has received about 3700 adverse event reports from Health Care Professionals and from consumers. In view of the great number of vaccinated individuals in Sweden and the limited number of adverse drug reaction reports and their pattern, the conclusion is that the safety of the vaccine in use is satisfactory.
About 8.7 million adult doses of Pandemrix have been delivered to the public medical service until January 8, according to the manufacturer. To the same point of time approximately 5.3 million individuals have been vaccinated, of which 600 000 were children 0-12 years of age, according to data from the Swedish Institute for Infectious Disease Control (SMI). The data from SMI also indicates that about 165 000 children have received a second dose of the vaccine.
The Medical Products Agency continuously publishes summaries of adverse events reported with Pandemrix. The summaries focus on reports relating to previously unknown or suspected serious side effects while the known adverse and mild events are reported only briefly.
In the present summary information is gathered both covering the cumulative period until January 7, 2010 and in some cases the latest period between December 4 and January 7. This summary specifically addresses reports from Health Care Professionals on allergic reactions, neurological reactions, reactions in children and in pregnant women and deaths. Included is also a short summary regarding the reporting of adverse events on a European level. As a result of that the number of vaccinated people will most likely decrease, this will also affect the reporting of adverse events.
Reports from Health Care Professionals
More than 1700 reports have been received from Health Care Professionals. Only 20% of the reports describe adverse events that have been classified as being serious. The majority of the adverse events reported are expected and mild reactions such as injection site reactions and influenza like symptoms.
Of importance for the interpretation of adverse events reports
A report of an adverse event is often valid for a single individual but may comprise the description of more than one reaction. An assessment is made in order to evaluate the possible relationship of the reaction to the vaccination. Consideration is taken to the patient´s medical history, concomitant drug therapy and the temporal relationship to the adverse event.
The degree of seriousness of the event is also evaluated. Serious adverse events are normally defined as being life threatening, leading to hospitalisation or prolongation of hospitalisation, to disability or miscarriage or a fatal outcome.
When the follow up measures for Pandemrix, from a safety point of view, were intensified during the autumn the health care professionals were encouraged to report all suspected adverse events with the exception of those described as common/very common in the summary of product characteristics. Since the reporting is made already at the stage of suspicion the reporter does only have to acknowledge a time course, but not to consider whether there is a causal association.
A functioning system for reporting on adverse events is a valuable complement to the knowledge of adverse events that were known at the time of approval of the vaccine and is of great importance for elucidation of the risk profile.
The reporting pattern as a whole is still consistent with what has been seen from the clinical trials, with the exception of certain allergic and neurological reactions, which were observed only after the vaccination had started.
Comments on certain types of reactions
Allergic reactions
Allergic/anaphylactic reactions after vaccination with Pandemrix have been reported in the same frequency as previously described. No new or significant adverse events have occurred.
Allergic reactions have also been observed in the reports from other countries in Europe. This has resulted in an update of the product information (SPC/PL) for Pandemrix with this information.
Neurological reactions
A total of 618 neurologic adverse events have been reported, of which 129 were assessed as serious. The majority of the serious reactions reported continue to be dizziness (19), fainting/syncope (18) and paresthesia (14) which has most commonly occurred in the setting of allergic or vaso-vagal reactions.
Hitherto 41 reactions of sensory disturbances have been reported. Only 5 of them were assessed as serious. One individual had a previous medical history with polyneuropathy. Follow up of three of the reports is still ongoing. Of a total of 24 reports of convulsions, 14 have been assessed as serious and in 21 cases the patients were younger than 18 years of age.
There have been a total of 13 reports of facial palsy, of which four have been reported since the last summary. In six of the cases assessed as serious an association with the vaccination cannot be excluded.
Until now a total of 5 reports of Guillain-Barré syndrome (GBS) have been received. Three cases concerned elderly individuals with underlying medical conditions and two of the cases involved healthy individuals. In all cases the onset of symptoms occurred within 3 weeks of vaccination. According to the reports all patients recovered after treatment. The total number of reports on GBS is lower than would be expected considering the size of the vaccinated population.
During the current reporting period a case involving a 6 year old boy who was diagnosed with acute disseminated encephalomyelitis approximately 26 days after vaccination was received. The condition of the patient improved after treatment.
Adverse reactions reported in children
As of January 8, 2010 at least 121 000 children younger than 3 years, and about 480 000 children aged 3 years up to 13 years, in Sweden have been vaccinated with the first dose of Pandemrix. This estimate is based on data from the Swedish Institute for Infectious Disease Control (SMI). Additionally there is information that about 165 000 children had received the second dose of the vaccine.
About one fourth of all reports received from Health Care Professionals involved children (0-17 years of age). In about one fifth of the reports the reactions have been classified as serious.
Since the last summary an additional 27 cases with serious reactions in children (0-17 years of age) have been received: 16 cases concerned children younger than 10 years of age and 11 cases children over 11 years of age. The most frequently reported reaction was febrile convulsions (6 cases, of which 5 cases involved children below 2 years of age). The febrile convulsions have occurred in close association with the vaccination (the same day or the day after) and all subjects have recovered within short time. Other frequently reported reactions for children are neurological events and convulsions and petit mal epilepsy. One case of myelitis and one case of encephalomyelitis were also reported (see the section of neurological reactions). Additional reports on previously described allergic reactions were also received. Individual reports have described pain at the injection site, skin reactions (erythematous rash) and influenza like illness, pneumonia and renal dysfunctions (haematuria in one case and nephrotic syndrome in one case).
The most commonly reported serious adverse events in children, reported from Health Care Professionals, are still neurological reactions (e.g. febrile convulsions/seizures and syncope), immunological reactions (e.g. anaphylactic/allergic reactions) or general symptoms (e.g. fever and influenza like illness). The pattern is similar to that described in previous summaries of adverse events.
Adverse reactions in pregnant women
The exact numbers of vaccinated pregnant women in different parts of Sweden are not definitely accounted for. However, as of December 4, based on data from the Swedish Institute for Infectious Disease Control (SMI), more than 31 000 pregnant women had been vaccinated with Pandemrix. A total of 42 reports of suspected adverse reactions in pregnant women in connection to vaccination have been received from Health Care Professionals. The comprehensive overview demonstrated that the pattern of adverse events in pregnant women is the same as previously and no new or unexpected events were observed.
A total of 22 women experienced miscarriages according to the reports (12 reports from Health Care Professionals and 10 reports from consumers) in temporal association with the vaccination with Pandemrix, 15 cases in the first trimester of the pregnancy and 6 in the second. In addition, 5 women reported intrauterine foetal deaths (from gestational age week 24). In one woman the intrauterine foetal death occurred in the gestational week 24, for another woman in week 33 and for three women at full time pregnancy. In two cases the follow up is still pending.
The evaluation of the specific reports does not give reason to conclude that the vaccine has caused neither the miscarriages nor (awaiting the final results of the investigation) the foetal deaths. Although these reports do not include all actual cases after vaccination, due to known underreporting of adverse events, the number probably is considerably lower than what would be expected from statistics regarding miscarriages or intrauterine foetal deaths. Miscarriages may occur in 10-15% of all early verified pregnancies and intrauterine foetal deaths occurred at a size of 3 cases per 1000 born babies in 2007.
In Europe as a whole at least 220 000 pregnant women have been vaccinated with pandemic vaccines, of which a great number with the same vaccine (Pandemrix) as used in Sweden. A summary and an assessment of all known reports of miscarriage or intrauterine foetal death within the EU have so far not given any cause to suspect that pandemic vaccination would increase such a risk.
In conclusion, a large number of pregnant women have been vaccinated at different stages of the pregnancy. The proportionally low number of reports and with no defined risk profile this would indicate that the vaccination with Pandemrix does not increase the risk for a negative outcome of pregnancy.
Deaths reported
As of January 8, 2010 a total of 20 deaths have been reported, of which two are new reports since the previous summary published on December 11. Some of the previously reported cases are still under investigation. In this summary only the new cases are commented.
One of the new cases involves a man (40 years of age) which died in his sleep 4 days after vaccination. From what has emerged so far, there is no information that confirms a causal association between the vaccination and the death, but an autopsy is requested for further assessment of the possible cause of death.
The other case concerns a 22 year old female with Retts syndrome, colitis ulcerosa, epilepsy and a recently diagnosed collum fracture who seeked healthcare due to cough, fever and convulsions. The patient was treated with antibiotics, improved temporarily but subsequently deteriorated, and became anoxic and tachypnoic due to interstitial pneumonitis. The patient died and the rapporteur could not exclude an association with Pandemrix which was given 2 days before hospitalisation.
Experience from consumer reporting
Since the vaccination campaign with Pandemrix began in Sweden on October 12, more than 2000 consumer reports of suspected adverse reactions have been received by the Medical Products Agency. About 260 reports have been received since the last published summary in December. About 25 of these 260 reports include adverse events that have been classified as serious.
Among the 33 serious events recently reported by consumers there are 6 cases of miscarriages at an early stage of the pregnancy and one case of intrauterine foetal death. Two cases of thrombocytopenia in children which have been diagnosed and treated in a pediatric clinic and moreover two cases of facial palsy and three cases of visual disturbances have also been reported. One case with Guillain-Barré syndrome has been reported both via the consumer reporting system and from health care professionals.
The reported non-serious reactions are as previously, mainly flu-like symptoms, significant and/or long lasting pains at the injection site (the arm). Despite that the majority of the reports do not include serious reactions it is clear from the descriptions that in many cases it has caused considerable inconveniences.