ADJUPANRIX Emulsion for injection Ref.[50412] Active ingredients: Influenza, inactivated, split virus

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity

Caution is needed when administering this vaccine to persons with a known hypersensitivity (other than anaphylactic reaction) to the active substance, to any of the excipients listed in section 6.1, to thiomersal and to residues (egg and chicken protein, ovalbumin, formaldehyde, gentamicin sulphate and sodium deoxycholate).

Concurrent illness

If the pandemic situation allows, immunisation shall be postponed in patients with severe febrile illness or acute infection.

Thrombocytopenia and coagulation disorders

Adjupanrix should under no circumstances be administered intravascularly. There are no data with Adjupanrix using the subcutaneous route. Therefore, healthcare providers need to assess the benefits and potential risks of administering the vaccine in individuals with thrombocytopenia or any bleeding disorder that would contraindicate intramuscular injection unless the potential benefit outweighs the risk of bleedings.

Protection

There are no data on administration of AS03-adjuvanted vaccines before or following other types of influenza vaccines intended for pre-pandemic or pandemic use.

Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.

A protective immune response may not be elicited in all vaccinees (see section 5.1).

Syncope

Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints.

Narcolepsy

Epidemiological studies relating to another AS03-adjuvanted vaccine (Pandemrix H1N1, also manufactured in the same facility as Adjupanrix), in several European countries have indicated an increased risk of narcolepsy with or without cataplexy in vaccinated as compared with unvaccinated individuals. In children/adolescents (aged up to 20 years), these studies have indicated an additional 1.4 to 8 cases in 100 000 vaccinated subjects. Available epidemiological data in adults aged over 20 years have indicated approximately 1 additional case per 100 000 vaccinated subjects. These data suggest that the excess risk tends to decline with increasing age at vaccination. Narcolepsy has not been observed in clinical trials with Adjupanrix, however clinical trials are not powered to detect very rare adverse events with incidence rates as low as narcolepsy (≈ 1.1/100,000 Person-Years).

Paediatric population

Clinical data in children less than 6 years of age who received two doses of pandemic preparedness influenza vaccine (H5N1) indicate an increase in frequency of fever (axillary≥38°C) after the administration of the second dose. Therefore, monitoring of temperature and measures to lower the fever (such as antipyretic medication as seems clinically necessary) are recommended in young children (e.g. up to approximately 6 years of age) post-vaccination.

Sodium and potassium content

This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodiumfree’.

This vaccine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially ‘potassium-free’.

There are no data on co-administration of Adjupanrix with other vaccines. If co-administration with another vaccine is considered, immunisation should be carried out on separate limbs. It should be noted that the adverse reactions may be intensified.

The immunological response may be diminished if the patient is undergoing immunosuppressant treatment.

Following influenza vaccination, false-positive serology test results may be obtained by the ELISA method for antibody to human immunodeficiency virus-1 (HIV-1), hepatitis C virus and, especially, HTLV-1. In such cases, the Western blot method is negative. These transitory false-positive results may be due to IgM production in response to the vaccine.

Pregnancy

There are currently no data available on the use of Adjupanrix in pregnancy.

An AS03-containing vaccine containing HA from H1N1v has been administered to women in each trimester of pregnancy. Information on outcomes from estimated more than 200 000 women who have been vaccinated during pregnancy is currently limited. There was no evidence of an increased risk of adverse outcomes in over 100 pregnancies that were followed in a prospective clinical study.

Animal studies with Adjupanrix do not indicate reproductive toxicity (see section 5.3).

Data from pregnant women vaccinated with different inactivated non-adjuvanted seasonal vaccines do not suggest malformations or foetal or neonatal toxicity. The use of Adjupanrix may be considered during pregnancy if this is thought to be necessary, taking into account official recommendations.

Breast-feeding

Adjupanrix may be used in lactating women.

Fertility

No fertility data are available.

Some of the effects mentioned under section 4.8 “Undesirable Effects” may affect the ability to drive or operate machinery.

Summary of the safety profile

Clinical studies have evaluated the incidence of adverse reactions listed below in approximately 5 000 subjects 18 years old and above who received formulations of H5N1 vaccine containing A/Vietnam/1194/2004 (H5N1) strain with at least 3.75 microgram HA/AS03.

Two clinical studies evaluated the incidence of adverse reactions in approximately 824 children aged 3 to <18 years who received half the adult dose, 0.25 mL, containing A/Indonesia/2005 (H5N1) strain with at least 1.9 microgram HA/AS03.

Three clinical studies evaluated the incidence of adverse reactions in approximately 437 children aged 6 months to <36 months who received either half the adult dose (n=400), 0.25 mL, or a quarter adult dose, 0.125 mL (n=37).

List of adverse reactions

Adverse reactions reported are listed according to the following frequency:

Frequencies are reported as: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1 000 to <1/100), Rare (≥1/10 000 to <1/1 000), Very rare (<1/10 000).

Adverse reactions from clinical trials with the pandemic preparedness vaccine are listed here below (see section 5.1 for more information on pandemic preparedness vaccines).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Adults

The following adverse reactions per dose have been reported:

Paediatric population

The following adverse reactions per dose have been reported:

Children 6 to <36 months

Data for this age group is derived from a pooling of safety data from 3 studies (D-PAN-H5N1-013, Q-PAN-H5N1-021 and Q-PAN-H5N1-023).

¹ A higher frequency of fever occurred following dose 2 compared to dose 1 in each age group.

Children 36 months to <18 years

Data for this age group is derived from a pooling of safety data from 2 studies (D-PAN-H5N1-032 and Q-PAN-H5N1-021).

¹ A higher frequency of fever occurred following dose 2 compared to dose 1 in each age group.
NR=Not reported

Similar reactogenicity results were obtained in a clinical study (D-PAN-H5N1-009) that was conducted in children 3 to 5 and 6 to 9 years of age; of whom 102 subjects received 2 doses of 0.25 ml of Adjupanrix; in this study fever was common with no increase in incidence seen after the second primary dose. In addition, the following adverse reactions were also observed: ecchymosis at the injection site, shivering and sweating increased. All three reactions were common.

Post-marketing surveillance

No post-marketing surveillance data are available following Adjupanrix administration.

AS03-containing vaccines containing 3.75 µg HA derived from A/California/7/2009 (H1N1)

From post-marketing experience with AS03-containing vaccines containing 3.75 µg HA derived from A/California/7/2009 (H1N1), the following adverse reactions have been reported:

Immune system disorders: Anaphylaxis, allergic reactions

Nervous system disorders: Febrile convulsions

Skin and subcutaneous tissue disorders: Angioedema, generalised skin reactions, urticaria

Interpandemic trivalent vaccines

In addition, from post-marketing surveillance with interpandemic trivalent vaccines, the following adverse reactions have been reported:

Rare: Neuralgia, transient thrombocytopenia.

Very rare: Vasculitis with transient renal involvement.

Neurological disorders, such as encephalomyelitis, neuritis and Guillain Barré syndrome.

This medicinal product contains thiomersal (an organomercuric compound) as a preservative and therefore, it is possible that sensitisation reactions may occur (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.