Daronrix - summary of medicine characteristics

1. NAME OF THE MEDICINAL PRODUCT

Daronrix, suspension for injection in pre-filled syringe

Pandemic influenza vaccine (whole virion, inactivated, adjuvanted)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Whole virion influenza vaccine of pandemic strain, inactivated, containing antigen* equivalent to:

per 0.5 ml dose

propagated in eggs

haemagglutinin

adjuvanted by aluminium phosphate and aluminium hydroxide, hydrated

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

Excipients:

50 micrograms

For a full list of excipients see section 6.1.

3. PHARMACEUTICAL FORM

Suspension for injection.

Turbid white suspension.

4. CLINICAL PARTICULARS4.1 Therapeutic indications

Prophylaxis of influenza in an officially declared pandemic situation. Pandemic influenza vaccine should be used in accordance with official guidance. (see sections 4.2 and 5.1)

4.2 Posology and method of administration

Daronrix has been evaluated with a haemagglutinin content of 15 ^g HA per dose in adults aged 18–60 years following a 0, 21 day schedule.

Adults from the age of 18 to 60 years will receive two doses of Daronrix, the first administered at an elected date, the second at least three weeks after the first dose for maximum efficacy.

No data have been generated with Daronrix below 18 years of age. Therefore health care providers need to assess the benefits and potential risks of administering the vaccine in that population.

For pregnant women, see section 4.6.

For further information, see section 5.1.

Immunisation should be carried out by intramuscular injection.

4.3 Contraindications

History of an anaphylactic reaction (i.e. life-threatening) to any of the constituents or trace residues (e.g. eggs, chicken protein, gentamicin sulphate) of this vaccine. However, in a pandemic situation, it may be appropriate to give the vaccine, provided that facilities for resuscitation are immediately available in case of need.

See section 4.4.

4.4 Special warnings and precautions for use

Caution is needed when administrating this vaccine to persons with a known hypersensitivity (other than anaphylactic reaction) to the active substance, to any of the excipients, to thiomersal and to residues e.g. eggs, chicken protein, gentamicin sulphate.

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.

Daronrix should under no circumstances be administered intravascularly.

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).

4.5 Interaction with other medicinal products and other forms of interaction

Daronrix should not be given at the same time as other vaccines. However, if co-administration with another vaccine is indicated, 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 results in serology tests using the ELISA method to detect antibodies against HIV-1, Hepatitis C and especially HTLV-1 have been observed. The Western Blot technique disproves the results. The transient false positive reactions could be due to the IgM response by the vaccine.

• 4.6 Pregnancy and lactation

No data have been generated with Daronrix in pregnant women. Therefore health care providers need to assess the benefits and potential risks of administering the vaccine to pregnant women taking into consideration official recommendations. Data from vaccinations with interpandemic trivalent vaccines in pregnant women do not indicate that adverse foetal and maternal outcomes were attributable to the vaccine.

Daronrix may be used during lactation.

4.7 Effects on ability to drive and use machines

The vaccine is unlikely to produce an effect on the ability to drive and use machines.

4.8 Undesirable effects

• • Clinical trials

Adverse reactions from clinical trials with different formulations (H5N1, H2N2 and H9N2) (N=941) of the mock-up vaccine are listed here below (see section 5.1 for more information on mock-up vaccines). Two hundred and one subjects received the monovalent aluminium-adjuvanted whole virus vaccine (A/H5N1).

The incidence of symptoms observed in subjects >60 years of age was lower as compared to the 18–60 years old population.

Undesirable effects 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)

Not known (cannot be estimated from the available data)

Infections and infestations

Uncommon: nasopharyngitis, rhinitis

Nervous system disorders

Very common: headache

Skin and subcutaneous tissue disorders

Common: sweating increase, ecchymosis

Musculoskeletal and connective tissue disorders

Common: myalgia, arthralgia

General disorders and administration site conditions

Very common: pain and redness at the site of injection, fatigue

Common: swelling and induration at the site of injection, shivering, fever

Uncommon: injection site pruritis

These reactions usually disappear within 1–2 days without treatment.

• • Post-marketing surveillance

From Post-marketing surveillance with interpandemic trivalent vaccines, the following adverse events have been reported:

Uncommon (>1/1,000 to <1/100):

Generalised skin reactions including pruritus, urticaria or non-specific rash.

Rare (>1/10,000 to <1/1,000):

Neuralgia, paraesthesia, convulsions, transient thrombocytopenia.

Allergic reactions, in rare cases leading to shock, have been reported.

Very rare (<1/10,000):

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).

4.9 Overdose

No case of overdose has been reported.

5. PHARMACOLOGICAL PROPERTIES5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Influenza vaccines, ATC Code J07BB01.

This section describes the clinical experience with the mock-up vaccines following a two-dose administration.

Mock-up vaccines contain influenza antigens that are different from those in the currently circulating influenza viruses. These antigens can be considered as “novel” antigens and simulate a situation where the target population for vaccination is immunologically naïve. Data obtained with the mock-up vaccine will support a vaccination strategy that is likely to be used for the pandemic vaccine: clinical immunogenicity, safety and reactogenicity data obtained with mock-up vaccines are relevant for the pandemic vaccines.

A clinical study has evaluated the immunogenicity of the monovalent aluminium-adjuvanted whole virus vaccine (A/H5N1) with a haemagglutinin content of 15 ^g HA per dose in adults aged 18–60 years (N=48) following a 0, 21 day schedule.

The seroprotection rate, the seroconversion rate and seroconversion factor for anti-HA antibody were as follows:

anti-HA antibody	21 days after 1st dose	21 days after 2nd dose
Seroprotection rate*	50.0% (95% CI: 35.2;64.8)	70.8% (95% CI: 55.9;83.0)
Seroconversion rate	47.9% (95% CI: 33.3;62.8)	70.8% (95% CI: 55.9;83.0)
Seroconversion factor	6 (95% CI: 3.5;10.1)	12.4 (95% CI: 7.1;21.8)

* anti-HA >1:40

In this clinical study, the immunogenicity of the monovalent aluminium-adjuvanted whole virus vaccine (A/H5N1) with a haemagglutinin content of 27^g HA per dose in adults aged 18–60 years (N=49) was also evaluated following a 0, 21 day schedule.

The seroprotection rate, the seroconversion rate and seroconversion factor for anti-HA antibody were as follows 21 days after the first dose:

anti-HA antibody	21 days after 1st dose
Seroprotection rate*	73.5% (95% CI: 58.9;85.0)
Seroconversion rate	69.4% (95% CI: 54.6;81.7)
Seroconversion factor	14.5 (95% CI: 8.3;25.4)

* anti-HA >1:40

No clinical data have been generated in subjects below 18 years of age.

Although no clinical data have been generated with Daronrix in subjects >60 years of age, the immunogenicity of a mock up formulation with different antigen doses of an aluminium-adjuvanted whole virus vaccine (A/H9N2) administered at 0, 21 days was evaluated in a clinical trial in this population. These results indicated that higher antigen content may be needed in subjects above 60 years of age as compared to an adult population (18–60 years) in order to ensure optimal protection.

The persistence of antibodies for the mock-up vaccines varies. With interpandemic trivalent vaccines, it is usually 6 – 12 months, but for Daronrix no data are available yet with the H5N1 strain.

In a clinical study where a mock-up formulation of aluminium-adjuvanted whole virus vaccine (AH9/N2) containing 3.8 ^g HA was evaluated following a 0, 10 day schedule, it has been shown that a faster onset of protection could be reached as compared to the recommended 0, 21 day schedule.

However data suggested that the duration of protection might be shorter. In circumstances when a fast onset of protection is needed, a third dose might therefore be necessary to ensure duration of protection.

Daronrix has been authorised under “Exceptional Circumstances”.

This means that for scientific reasons, it has not been possible to obtain complete information on this medicinal product.

The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Not applicable.

6. PHARMACEUTICAL PARTICULARS6.1 List of excipients

Sodium chloride

Disodium phosphate dodecahydrate

Potassium dihydrogen phosphate

Potassium chloride

Magnesium chloride hexahydrate

Thiomersal

Water for injections

For adjuvants, see section 2.

6.2 Incompatibilities

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

• 6.3 Shelf-life 1 year.

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.

6.5 Nature and contents of container

0.5 ml in pre-filled syringe (type I glass) with a plunger stopper (butyl) for 1 dose – pack sizes of 1 and 10 with or without needles.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

The vaccine should be allowed to reach room temperature before use. Shake before use.

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