The Public Health Agency of Canada recommends two half-doses of adjuvanted H1N1 flu vaccine, given at least 21 days apart, for children six months to three years old. (Pawel Dwulit/Canadian Press)

Children up to three years of age who received a second dose of H1N1 vaccine may be more likely to develop a fever, the European Medicines Agency said Friday.

The European drug regulator said data from the vaccine's manufacturer, GlaxoSmithKline, showed a higher incidence of fever following the second dose of Pandemrix than after the first dose, based on early results on a sample of 51 infants.

The pediatric study is ongoing, and more data from this trial and others will be available shortly, the agency said in a statement.

Young children were also more likely to show side-effects such as muscle pain, drowsiness, irritability and loss of appetite.

Prescribers and parents should monitor the temperature of the vaccinated child. If needed, the European regulator advised caregivers to take measures to lower the fever, such as giving a fever reducing medicine.

The agency recommended that the latest information be included in prescribing information for the vaccine, and be taken into consideration when deciding whether to give a second dose to children.

Nearly 18 million doses given

"As stated by the [European Medicines Agency] the benefit/risk profile of Pandemrix in infants remains unchanged," GlaxoSmithKline said in a statement. "To date, no unexpected serious safety issues have been identified."

Worldwide, the company estimated almost 18 million doses of its H1N1 vaccine have been given in 26 countries.

Canada also uses an H1N1 vaccine from GSK, known as Arepranix H1N1.

Officials at the Public Health Agency of Canada did not immediately respond to questions from CBC News about whether higher rates of fever after a second dose of the vaccine have also been observed in Canada.

Federal health officials recommend that children ages six months to three years receive two half-doses of H1N1 vaccine containing an adjuvant or booster, given at least 21 days apart.

An adjuvant is added to a vaccine to stimulate a stronger immune response.

For healthy older children, one dose of the vaccine is needed, Dr. David Butler-Jones, Canada's chief public health officer, said last month.

Canada's recommendations were based on the results of clinical trials from Europe, where recommendations on a second dose vary from country to country.

The latest European study showed a single dose of vaccine triggered a good immune response in young children, but that the second dose further increased the immune response.

Severe reactions not higher than normal

Last month, GSK advised provicial health authorities not to use one batch of its Canadian-manufactured swine flu vaccine in case it triggered life-threatening side-effects like anaphylactic shock.

The Public Health Agency of Canada said Friday there have been 48 cases of a severe allergic reaction reported in people who have had H1N1 shots, as of the week of Nov. 20 when nearly 12.3 million doses of vaccine had been distributed across the country.

The rate of anaphylactic reactions is 0.39 per 100,000 doses, which the agency said doesn't exceed the normal rate seen for the administration of vaccines.

Anaphylaxis is the type of severe allergic reaction seen in people with severe food or insect sting allergies, and must be treated quickly with adrenaline.

Canada's public health agency said one of the cases of anaphylaxis was fatal and is being investigated. The investigation into the lot is also ongoing.

With files from The Canadian Press and The Associated Press