This is the statement of the Danish Medicines Agency following close scrutiny of all 174 reported adverse reactions from the new HPV vaccine against cervical cancer – Gardasil®. The adverse reactions were reported during the period from 20 September 2006 to 31 December 2008. In 2008 alone, almost 230,000 batches of vaccine were dispensed, corresponding to the vaccination of more than 75,000 young women.
The majority of the adverse reactions are well-known and specified in the summary of product characteristics which, among other things, describes the properties of the medicine. In addition to these, most of the adverse reactions are attributable to the vaccination itself, not the vaccine.
No indications of correlation between Gardasil® and infantile eczema
The experts of the Danish Medicines Agency reviewed all Danish and foreign adverse reaction reports in February 2009. On the basis of this material, there are no indications of a correlation between infantile eczema (atopic dermatitis) and Gardasil®.
The suspicion arose after a Danish doctor reportedly observed several cases of recrudescence of infantile eczema in girls vaccinated with Gardasil®. Infantile eczema is a relatively widespread disease. It is also a disease susceptible to recrudescence. Therefore, it is not surprising to see a number of instances of coincidence between vaccination and debut or recrudescence of infantile eczema.
In January 2009, the Danish Medicines Agency received one report on infantile eczema. This report will form part of the overview of adverse reactions from the first quarter of 2009. The Danish Medicines Agency will closely monitor any new reports on infantile eczema as well as any reports from other medicines agencies in the EU.
The Danish Medicines Agency and the National Board of Health are monitoring Gardasil® closely
In future, all 12-year old girls will be offered the vaccine, and in collaboration with the National Board of Health, the Danish Medicines Agency will be monitoring any adverse reactions from Gardasil® closely. In this connection, the Danish Medicines Agency encourages all general practitioners to report any observed adverse reactions via meldenbivirkning.dk (or their practice system). At meldenbivirkning.dk, patients and relatives can also report side effects.
If the Danish Medicines Agency receives information about new suspected adverse reactions, this information will be examined closely in collaboration with the marketing authorisation holder and the medicines agencies of the other EU countries. Similarly, the Danish Medicines Agency is monitoring reports on adverse reactions from the other EU countries. In Spain, there were two cases of unexpected adverse reactions, where the women, following vaccination, went into violent seizures are were admitted to hospital. The Spanish authorities are will initially look at the vaccine batch used. This has been withdrawn, and no vaccines from this batch have been used in Denmark.
The Danish Medicines Agency reports four times a year
In future, the Danish Medicines Agency will publish an overview of adverse reactions from Gardasil from general practitioners, other healthcare professionals and consumers approx. four times a year. The overview below is the first of these.
Adverse reaction reports from 20 September 2006 to 30 September 2008
Adverse reaction reports from 1 October 2008 to 31 December 2008
Background information about cervical cancer and Gardasil®
General information about adverse reaction data
Top
Adverse reaction reports from 20 September 2006 to 30 September 2008
Since Gardasil® was introduced on the Danish market in September 2006 and up to 30 September 2008, the Danish Medicines Agency has received 42 adverse reaction reports containing a total of 74 adverse reactions. During this period, more than 25,000 young women were vaccinated. The most frequent adverse reactions are all well-known and specified in the summary of product characteristics:
- temperature increase (10%)
- nausea (6%)
- dizziness (6%)
- headache (5%)
- urticaria (5%)
Six of the reports describe unexpected and potentially serious adverse reactions. Read more about the different adverse reactions later in this overview, where the six cases are also described.
Adverse reaction reports from 1 October 2008 to 31 December 2008
On 1 October 2008, general practitioners started vaccinating girls born in 1993, 1994 and 1995 as part of a pilot programme running until the end of the year. After this, Gardasil was made part of the childhood immunisation programme for girls aged 12. From 1 October 2008 to 31 December 2008, the Danish Medicines Agency received 48 adverse reaction reports containing a total of 100 adverse reactions. During this period, vaccines were dispensed corresponding to the vaccination of approx. 50,000 women.
Most of the adverse reactions are known and are already specified in the summary of product characteristics. In addition to these, almost all the adverse reactions were attributable to the vaccination itself, not the vaccine. Six reports describe serious adverse reactions (e.g. hospitalisation), but there are no indications of new, serious adverse reactions from Gardasil®. As expected, the most common adverse reactions are:
- headache (8%)
- nausea (7%)
- temperature increase (5%)
- dizziness (5%)
- urticaria (5%)
The most frequent adverse reactions from 1 October to 31 December 2008 have been categorised into five tables with the following headings:
- Reactions at the injection site
- Allergic reactions
- Psychogenic reactions
- Other known adverse reactions
- Unknown adverse reactions according to the summary of product characteristics
Top
Reactions at the injection site
| Adverse reaction |
Quantity |
|
Swelling |
5 |
|
Redness |
2 |
|
Nodule |
2 |
|
Pain |
1 |
|
Itching |
1 |
|
Accumulation of blood |
1 |
Allergic reactions
| Adverse reaction |
Quantity |
|
Urticaria |
6 |
|
Redness |
3 |
|
Itching |
3 |
|
Rash |
2 |
|
Swelling around the eyes |
1 |
|
Hard infiltration |
1 |
|
Facial swelling |
1 |
|
Erythema nodosum |
1 |
|
Anaphylactic chock |
1 |
Psychogenic factors
Adverse reaction |
Quantity |
|
Fainting |
2 |
|
Near fainting |
1 |
Other known adverse reactions
Adverse reaction |
Quantity |
|
Headache |
10 |
|
Nausea |
8 |
|
Dizziness |
6 |
|
Fever |
5 |
|
Discomfort |
5 |
|
Pain |
3 |
|
Muscle pain |
2 |
|
Paleness |
2 |
|
Influenza-like symptoms |
2 |
|
Vomiting |
2 |
|
Fainting |
2 |
|
Stomach ache |
2 |
|
Feeling of weakness |
1 |
|
Tingling sensation |
1 |
|
Swollen lymph nodes |
1 |
|
Musculoskeletal pain |
1 |
Unknown adverse reactions
– see comments to highlighted adverse reactions
| Adverse reaction |
Quantity |
|
Peripheral oedema |
1 |
|
Motor speech difficulties |
1 |
|
Chest pain |
1 |
|
Shaking |
1 |
|
Connective tissue disease (SLE)
SLE is a chronic disease characterised by e.g. facial rash, joint pain and affected renal function. One report describes a girl who was diagnosed with SLE approx. one month after her vaccination with Gardasil®. SLE is not a known adverse reaction from Gardasil®, and the Danish Medicines Agency is of the opinion that the connection is coincidental. |
1 |
|
Herpes zoster
Herpes zoster is an infectious disease which occurs when chickenpox virus is reactivated (often seen in case of a weakened immune system). One adverse reactions report describes a case of herpes zoster, following the first vaccination, in a girl who had had chickenpox as a child. The symptoms occurred four days after the vaccination. However, the girl was assessed to have a normal immune system. She was treated with Zovir®, and the herpes outbreak disappeared after 1-2 weeks of treatment. The general practitioner is planning to resume vaccinations with Gardasil®. Herpes zoster is not a known adverse reaction from Gardasil®. |
1 |
|
Diabetes
One adverse reaction report describes a girl who was diagnosed with diabetes approx. two weeks after the first vaccination with Gardasil®. Diabetes is not a known adverse reaction from Gardasil®, and the Danish Medicines Agency is of the opinion that the connection is coincidental. |
1 |
|
Cramps
One report describes a case of cramps in a girl who fainted shortly after the vaccination. She was fine again the next day. The girl had previously fainted when subjected to pain. The Danish Medicines Agency expects cramps to occur very rarely. |
1 |
|
Facial paralysis
One report describes a girls who suffered from left-sided facial paralysis. The paralysis occurred 18 days after the third and last vaccination. Paralysis is not a known adverse reaction from Gardasil®. The Danish Medicines Agency will ask the general practitioner for additional information. |
1 |
|
Breast swelling |
1 |
|
Breast soreness |
1 |
|
Cough |
1 |
|
Phlebitis
One report describes a girl who developed a rash on her legs, from the knees down, eight days after the vaccination. The general practitioner assessed the inflammation to be vasculitis and referred the girl to a dermatologist. The Danish Medicines Agency will ask the general practitioner for additional information. |
1 |
Top
Background information about cervical cancer and Gardasil®
Since 1 January 2009, the preventative vaccination against cervical cancer – HPV vaccination – has been a part of the Danish childhood immunisation programme. Denmark has selected the Gardasil® vaccine.
Cervical cancer is widespread in Denmark
The background for including the vaccine in the Danish childhood immunisation programme is that Denmark has one of the highest incidence rates of cervical cancer in the EU. In Denmark, more than 400 women are diagnosed with cervical cancer every year, and approx. 130 women die from the disease every year.
Causes of the disease
Cervical cancer is caused by an infection with certain types of HPV. The majority of the adult population has had an HPV infection at some time, and the carcinogenic types are predominant. Among more than 100 different types of HPV, types 16 and 18 cause the highest risk of cervical cancer. These types were observed in 70% of the women diagnosed with cervical cancer. Gardasil® prevents infection with HPV types 16 and 18.
Gardasil® prevents cervical cancer and condyloma
In addition to preventing infection with HPV types 16 and 18, Gardasil® also prevents infection with HPV types 6 and 11, which cause condyloma. Condyloma is a very common, annoying, but benign disease which, in 90% of cases, is caused by an infection with HPV types 6 and 11.
219,990 vaccines as of February 2009
From September 2008 to 6 February 2009, at total of 219,990 vaccine doses had been dispensed to the childhood immunisation programme (source: Statens Serum Institut). This would suffice to vaccinate more than 70,000 girls.
General information about adverse reaction data
An adverse reaction report contained in the pharmacovigilance database does not necessarily mean that there is a correlation (causality) between the medicinal product and the adverse reaction.
- The Danish Medicines Agency registers information about an adverse reaction in the database even if it is only suspected that there might be a correlation between the medicinal product and the adverse reaction. Therefore, the information in the database may include real adverse reactions from a medicinal product as well as random incidences due to e.g. a disease in the patient or another medicinal product 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 will usually be higher than the number of adverse reaction reports.
- An adverse reaction is considered to be serious if it leads to the patient’s death, disability, hospitalisation, 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 send to the Danish Medicines Agency regularly. A periodic safety update report describes all reported adverse reactions from all countries in which the medicinal product is marketed. The periodic safety update reports thus provide a good overview, and they form an important basis for continuous updates of summary of product characteristics and package leaflet.
For further information, please contact Chief Medical Officer Steffen Thirstrup, tel. +45 2246 7811.
Danish Medicines Agency, 11 March 2009
Top
