Pumarix - summary of medicine characteristics

2. QUALITATIVE AND QUANTITATIVE COMPOSITIONmicrograms

After mixing, 1 dose (0.5 ml) contains:

Split influenza virus, inactivated, containing antigen* equivalent to:

A/Indonesia/05/2005 (H5N1) like strain used (PR8-IBCDC-RG2) 3.75

*

propagated in eggs

**

haemagglutinin

This vaccine complies with the WHO recommendation and EU decision for the pandemic.

AS03 adjuvant composed of squalene (10.69 milligrams), DL-a-tocopheiol (11.86 milligrams) and polysorbate 80 (4.86 milligrams)

The suspension and emulsion, once mixed, form a multidose vaccine in a vial. See section 6.5 for the number of doses per vial.

Excipient with known effect: the vaccine contains 5 micrograms thiomersal

For the full list of excipients see section 6.1.

3. PHARMACEUTICAL FORM

Suspension and emulsion for emulsion for injection.

The suspension is a translucent to off white opalescent suspension, which may sediment slightly.

The emulsion is a whitish homogeneous liquid.

4. CLINICAL PARTICULARS4.1 Therapeutic indications

Prophylaxis of influenza in an officially declared pandemic situation (see sections 4.2 and 5.1).

Pandemic influenza vaccine should be used in accordance with official guidance.

4.2 Posology and method of administration

Posology

Adults from the age of 18 years onwards:

One dose of 0.5 ml at an elected date.

A second dose of 0.5 ml should be given after an interval of at least three weeks.

Persons previously vaccinated with one or two doses of AS03-containing vaccine containing HA derived from a different clade of the same subtype

Adults from the age of 18 years onwards: one dose of 0.5 ml at an elected date.

Paediatric population

There are very limited safety and immunogenicity data available on the administration of an AS03-adjuvanted vaccine containing 3.75 ^g HA derived from A/Vietnam/1194/2004 (H5N1) manufactured using a different process and on administration of half a dose of the same vaccine (i.e. 1.875 ^g HA and half the amount of AS03 adjuvant) at 0 and 21 days in children aged 3 to 9 years. See sections 4.8 and 5.1.

The safety and efficacy of Pumarix in children aged less than 3 years and in children and adolescents aged 10 to 17 years have not been established. No data are available.

For further information, see section 5.1.

It is recommended that subjects who receive a first dose of Pumarix, complete the vaccination course with Pumarix.

Method of administration

Immunisation should be carried out by intramuscular injection preferably into the deltoid muscle or anterolateral thigh (depending on the muscle mass).

For instructions on mixing of the medicinal product before administration, see section 6.6.

4.3 Contraindications

History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues (egg and chicken protein, ovalbumin, formaldehyde and sodium deoxycholate) of this vaccine. However, in a pandemic situation, it may be appropriate to give the vaccine provided that facilities for resuscitation should be immediately available in case of need.

4.4 Special warnings and precautions for use

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 and sodium deoxycholate).

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.

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

Pumarix should under no circumstances be administered intravascularly. There are no data with Pumarix 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.

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 (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.

Paediatric population

Clinical data in children less than 6 years of age who received two doses of another Pandemic influenza vaccine (H5N1 manufactured in Dresden, Germany) 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) postvaccination.

4.5 Interaction with other medicinal products and other forms of interaction

There are no data on co-administration of Pumarix 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.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are currently no data available on the use of Pumarix 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 Pumarix 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 fetal or neonatal toxicity.

The use of Pumarix may be considered during pregnancy if this is thought to be necessary, taking into account official recommendations.

Breast-feeding

Pumarix may be used in lactating women.

Fertility

No fertility data are available.

4.7 Effects on ability to drive and use machines

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

or use machines.

4.8 Undesirable effects

Summary of the safety profile

Clinical studies have evaluated the incidence of adverse reactions in approximately 4,500 subjects 18 years old and above who received Pumarix or placebo.

In adults 18 to 64 years of age, the most frequently reported adverse reactions after vaccination were injection site pain (80.5%), muscle aches (37.2%), fatigue (25.2%), headache (25.1%), joint pain (17.7%) and shivering (11.1%).

In subjects > 64 years of age, the most frequently reported adverse reactions after vaccination were injection site pain (58.0%), muscle aches (19.7%), fatigue (13.5%), headache (12.4%) and joint pain (10.3%).

List of adverse reactions

Adverse reactions reported are listed according to the following frequency:

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 mock-up vaccine are listed here below (see section 5.1 for more information on mock-up vaccines).

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

Blood, and lymphatic system disorders

Uncommon: lymphadenopathy

Psychiatric disorders

Uncommon: insomnia

Nervous system disorders

Very common: headache

Uncommon: dizziness, paraesthesia

Ear and labyrinth disorders Uncommon: vertigo

Respiratory, thoracic and mediastinal disorders

Uncommon: dyspnoea

Gastrointestinal disorders

Common: nausea, diarrhoea

Uncommon: abdominal pain, vomiting, dyspepsia, stomach discomfort

Skin and subcutaneous tissue disorders

Common: sweating

Uncommon: pruritus, rash

Musculoskeletal and connective tissue disorders

Very common: joint pain, muscle aches

Uncommon: back pain, musculoskeletal stiffness, neck pain, muscle spasms, pain in extremity

General disorders and administration site conditions

Very common: pain at the injection site, fatigue

Common: redness at the injection site, swelling at the injection site, fever, shivering

Uncommon: injection site reactions (such as bruising, induration, pruritus, warmth), asthenia, chest pain, malaise

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

From post-marketing experience with AS03-containing vaccines containing 3.75 ^g 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 disoi deis

Angioedema, generalised skin reactions, urticaria

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

Rare :

Neuralgia, transient thrombocytopenia.

Very r are:

Vasculitis with transient renal involvement.

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

Paediatric population

A clinical study (D-H5N1–009), evaluated the reactogenicity in children 3 to 5 and 6 to 9 years of age who received either two adult (i.e. 0.5 ml) doses or two half adult (i.e. 0.25 ml) doses (21 days apart) of another Pandemic influenza vaccine (H5N1 A/Vietnam/1194/2004 manufactured in Dresden, Germany).

The per-dose frequency of local and general solicited adverse reactions observed in the groups of children who received two adult (0.5 ml) doses was higher than that observed in the groups of children who received two half adult (i.e. 0.25 ml) doses, except for redness in the 6–9 years of age group. The administration of a second half adult or an adult dose did not enhance the reactogenicity, except for rates of general symptoms which were higher after the second dose, particularly for rates of fever in <6 year olds. The per-dose frequency of adverse reactions was as follows:

NA=not available

In other clinical studies where children 6 months to 17 years received another pandemic influenza vaccine (H5N1 A/Indonesia/05/2005 manufactured in Dresden, Germany), increases in the frequency of some side effects (including injection site pain, redness and fever) were seen after the second dose in children aged less than 6 years.

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).

4.9 Overdose

No case of overdose has been reported.

5. PHARMACOLOGICAL PROPERTIES5.1 Pharmacodynamic properties

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data obtained with Pumarix reveal no special hazard for humans based on conventional studies of safety pharmacology, acute and repeated dose toxicity, local tolerance, female fertility, embryo-fetal and postnatal toxicity (up to the end of the lactation period).

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Suspension vial:

Thiomersal

Sodium chloride (NaCl)

Disodium hydrogen phosphate (Na2HPO4)

Potassium dihydrogen phosphate (KH2PO4)

Potassium chloride (KCl)

Water for injections

Emulsion vial:

Sodium chloride (NaCl)

Disodium hydrogen phosphate (Na2HPO4)

Potassium dihydrogen phosphate (KH2PO4)

Potassium chloride (KCl)

Water for injections

For adjuvants, see section 2.

6.2 Incompatibilities

6.3   Shelf-life

6.4 Special precautions for storage

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Store in the original package in order to protect from light.

For storage conditions after mixing of the medicinal product, see section 6.3.

6.5 Nature and contents of container

One pack containing:

• – one pack of 50 vials (type I glass) of 2.5 ml suspension with a stopper (butyl rubber).

• – two packs of 25 vials (type I glass) of 2.5 ml emulsion with a stopper (butyl rubber).

The volume after mixing 1 vial of suspension (2.5 ml) with 1 vial of emulsion (2.5 ml) corresponds to 10 doses of vaccine (5 ml).

6.6 Special precautions for disposal and other handling

Pumarix consists of two containers:

Suspension: multidose vial containing the antigen, Emulsion: multidose vial containing the adjuvant.

Prior to administration, the two components should be mixed.

Instructions for mixing and administration of the vaccine :

• 1. Before mixing the two components, the emulsion (adjuvant) and suspension (antigen) should be brought to room temperature (allow a minimum of 15 minutes). Whitish sediments may be observed in the suspension vial; these sediments are part of the normal physical appearance of the suspension. The emulsion presents as a whitish appearance.

• 2. Each vial should be shaken and inspected visually for any foreign particulate matter (other than the white sediments described above) and/or abnormal physical appearance. In the event of either being observed (including rubber particles from the stopper), discard the vaccine.

• 3. The vaccine is mixed by withdrawing the entire contents of the vial containing the adjuvant by means of a 5 ml syringe and by adding it to the vial containing the antigen. It is recommended to equip the syringe with a 23-G needle. However, in the case this needle size would not be available, a 21-G needle might be used. The vial containing the adjuvant should be maintained in upside down position to facilitate the withdrawal of the full content.

• 4. After the addition of the adjuvant to the antigen, the mixture should be well shaken. The mixed vaccine is a whitish emulsion. In the event of other variation being observed, discard the

vaccine.

• 5. The volume of the Pumarix vial after mixing is at least 5 ml. The vaccine should be administered in accordance with the recommended posology (see section 4.2).

• 6. The vial should be shaken prior to each administration and inspected visually for any foreign particulate matter and/or abnormal physical appearance. In the event of either being observed (including rubber particles from the stopper), discard the vaccine.

• 7. Each vaccine dose of 0.5 ml is withdrawn into a 1 ml syringe for injection and administered intramuscularly. It is recommended to equip the syringe with a needle gauge not larger than 23G.

• 8. After mixing, use the vaccine within 24 hours. The mixed vaccine can either be stored in a refrigerator (2°C – 8°C) or at room temperature (25°C – 30°C). If the mixed vaccine is stored in a refrigerator, it should be brought to room temperature (allow a minimum of 15 minutes) before each withdrawal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

GlaxoSmithKline Biologicals s.a.

rue de l'Institut 89

B-1330 Rixensart, Belgium

8. MARKETING AUTHORISATION NUMBER(S)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 04 March 2011