Package Leaflet: Information for the User

Wyeth Pharmaceuticals

Huntercombe Lane South Taplow Maidenhead Berks SL6 0PH Telephone: +44 (0)1628 604 377 Facsimile: +44 (0)1628 666 368 Medical Information direct line: +44 (0)845 367 0098 Medical Information e-mail: [email protected] Medical Information facsimile: +44 (0)845 367 0777

Document last updated on the eMC: Fri 12 September 2008

Enzira Suspension for injection, pre-filled syringe/Influenza vaccine (split virion, inactivated) PH. Eur.

Table of Contents 1. NAME OF THE MEDICINAL PRODUCT 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 3. PHARMACEUTICAL FORM 4. CLINICAL PARTICULARS 4.1 Therapeutic indications 4.2 Posology and method of administration 4.3 Contraindications 4.4 Special warnings and precautions for use 4.5 Interaction with other medicinal products and other forms of interaction 4.6 Pregnancy and lactation 4.7 Effects on ability to drive and use machines 4.8 Undesirable effects 4.9 Overdose 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties 5.2 Pharmacokinetic properties 5.3 Preclinical safety data 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients 6.2 Incompatibilities 6.3 Shelf life 6.4 Special precautions for storage 6.5 Nature and contents of container 6.6 Special precautions for disposal and other handling 7. MARKETING AUTHORISATION HOLDER 8. MARKETING AUTHORISATION NUMBER(S) 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 10. DATE OF REVISION OF THE TEXT

1. NAME OF THE MEDICINAL PRODUCT

Enzira® Suspension for injection, pre-filled syringe Influenza vaccine (split virion, inactivated) Ph. Eur.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Split influenza virus*, inactivated with β-Propiolactone, containing antigens equivalent to: A/Brisbane/59/2007 (H1N1) - like strain 15 micrograms (A/Brisbane/59/2007 IVR-148) HA** A/Brisbane/10/2007 (H3N2) - like strain 15 micrograms (A/Uruguay/716/2007 NYMC X-175C) HA** B/Florida/4/2006 - like strain (B/Florida/4/2006) 15 micrograms HA** per 0.5 ml dose. * propagated in fertilised hens' eggs from healthy chicken flocks ** haemagglutinin This vaccine complies with the WHO recommendation (Northern Hemisphere) and EU decision for the 2008/2009 season. For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Suspension for injection in a pre-filled syringe. Clear to slightly opaque liquid with some sediment that resuspends upon shaking.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Prophylaxis of influenza, especially in those who run an increased risk of associated complications. The use of Enzira should be based on official recommendations.

4.2 Posology and method of administration

Posology Adults and children from 36 0.5 ml months: Children from 6 months to 35 Clinical data are limited. Dosages months: of 0.25 ml or 0.5 ml have been used. For children who have not previously been vaccinated, a second dose should be given after an interval of at least 4 weeks.

Method of administration

Immunisation should be carried out by intramuscular or deep subcutaneous injection. For instructions for preparation, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substances, to any of the excipients (see section 6.1), to eggs and/or chicken proteins. Enzira does not contain more than 1 µg ovalbumin per dose. The vaccine may contain residues of the following substances: neomycin, polymyxin. Immunisation shall be postponed in patients with febrile illness or acute infection.

4.4 Special warnings and precautions for use

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following administration of the vaccine. Enzira should under no circumstances be administered intravascularly. Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient. 4.5 Interaction with other medicinal products and other forms of interaction Enzira may be given at the same time as other vaccines. 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 serological tests using the ELISA method to detect antibodies against HIV1, Hepatitis C and especially HTLV1 have been observed. The Western Blot technique disproves the false-positive ELISA test results. The transient false positive reactions could be due to the IgM response to the vaccine.

4.6 Pregnancy and lactation

Pregnancy

The limited data from vaccination in pregnant women do not indicate that adverse fetal and maternal outcomes were attributable to the vaccine. The use of this vaccine may be considered from the second trimester of pregnancy. For pregnant women with medical conditions that increase their risk of complications from influenza, administration of the vaccine is recommended, irrespective of their stage of pregnancy.

Lactation

Enzira 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 Adverse reactions observed from clinical trials

The safety of trivalent inactivated influenza vaccines is assessed in open label, uncontrolled clinical trials performed as annual update requirements, including at least 50 adults aged 18 – 60 years of age and at least 50 elderly aged 61 years or older. Safety evaluation is performed during the first three days following vaccination. The following undesirable effects have been observed during clinical trials with the following frequencies: Very common (>1/10), common ( 1/100, <1/10), uncommon ( 1/1,000, <1/100), rare ( 1/10,000, <1/1,000), very rare (<1/10,000), including isolated reports. Organ class Very Common Uncommon Rare Very rare common >1/10 1/100, 1/1,000, 1/10,00 <1/10,000 <1/10 <1/100 0, <1/1,000 Nervous Headache* system disorders Skin and Sweating* subcutaneous tissue disorders Musculoskeletal Myalgia, and connective arthralgia* tissue disorders General Fever, disorders and malaise, administration shivering, site conditions fatigue.

Local reactions: redness, swelling, pain, ecchymosis, induration* * These reactions usually disappear within 1-2 days without treatment

Adverse reactions reported from post-marketing surveillance for trivalent influenza vaccines

Adverse reactions reported from post marketing surveillance for trivalent influenza vaccines are, next to the reactions which have also been observed during the clinical trials, the following:

Blood and lymphatic system disorders

Transient thrombocytopenia, transient lymphadenopathy

Immune system disorders

Allergic reactions, in rare cases leading to anaphylactic shock, angioedema

Nervous system disorders

Neuralgia, paraesthesia, convulsions Neurological disorders, such as encephalomyelitis, neuritis and Guillain- Barré syndrome

Vascular disorders

Vasculitis associated in very rare cases with transient renal involvement

Skin and subcutaneous tissue disorders

Generalised skin reactions including pruritus, urticaria or non-specific rash 4.9 Overdose Overdosage is unlikely to have any untoward effects.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07B B02 Seroprotection is generally obtained within 2 to 3 weeks. The duration of postvaccinal immunity to homologous strains or to strains closely related to the vaccine strains varies but is usually 6 to 12 months.

5.2 Pharmacokinetic properties Not applicable. 5.3 Preclinical safety data Not applicable.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride Anhydrous disodium phosphate Sodium dihydrogen phosphate dihydrate Potassium chloride Potassium dihydrogen phosphate Calcium chloride Water for injection

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 to 8°C). Do not freeze. Keep the syringe in the outer carton in order to protect from light.

6.5 Nature and contents of container

0.5 ml suspension in pre-filled syringe (Type I glass) with plunger stopper (chlorobutyl rubber) with attached needle in pack sizes of 1 or 10. Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling The vaccine should be allowed to reach room temperature before use. Shake before use. After shaking, the vaccine should appear as a homogenous suspension. The vaccine must be inspected visually prior to administration and should not be used if there is any variation of physical appearance (see section 3). Enzira is presented as a single use syringe and any remaining contents should be disposed of in compliance with local rules for the disposal of products of this nature. When a 0.25 ml dose is indicated, the pre-filled syringe should be held in an upright position and half the volume should be eliminated. To do so, depress the plunger to the half dose marking on the glass syringe barrel, the remaining volume should be injected.

7. MARKETING AUTHORISATION HOLDER

CSL Biotherapies GmbH Emil-von-Behring-Strasse 76 35041 Marburg Germany

8. MARKETING AUTHORISATION NUMBER(S)

PL 22236/0001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 19 April 2005

10. DATE OF REVISION OF THE TEXT

June 2008

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SUPPORTING INFORMATION

Patient Information Leaflet: Enzira suspension for injection, pre-filled syringe

Alternative format PIL: Enzira suspension for injection, pre-filled syringe (new window)

Medicine Guide: Enzira (new window) Enzira suspension for injection, pre-filled syringe In this leaflet:

PACKAGE LEAFLET: INFORMATION FOR THE USER

ENZIRA® Suspension for injection, pre-filled syringe Influenza vaccine (split virion, inactivated) Ph. Eur.

Read all of this leaflet carefully before you are given this vaccination.

 Keep this leaflet. You may need to read it again.  If you have any further questions, ask your doctor or pharmacist.  This vaccination has been prescribed for yourself, do not pass it on to others.  If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

 1. What Enzira is and what it is used for  2. Before you are given Enzira  3. How to use Enzira  4. Possible side effects  5. How to store Enzira  6. Further information

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1. WHAT ENZIRA IS AND WHAT IT IS USED FOR

Enzira is a suspension for injection in a pre-filled syringe. It contains a vaccine which stimulates the immune system to produce antibodies against influenza. The vaccine is used for prevention of influenza especially in those who run an increased risk of developing complications. The use of Enzira should be based on official recommendations. Full effect of the vaccine is generally achieved 2-3 weeks after the vaccination and the protection is usually maintained for 6 to 12 months.

2. BEFORE YOU ARE GIVEN ENZIRA Do not use Enzira

 If you are hypersensitive (allergic) to any of the ingredients of Enzira or to eggs and/or chicken proteins which includes ovalbumin, or the antibiotics neomycin or polymyxin.  If you have previously had an allergic reaction to this vaccine.  If you have a high fever or an acute infection.

Take special care with Enzira

Enzira will not work well if you suffer from a disease that lowers your immunity.

Inform your doctor if you have any known allergy or have previously had problems with vaccinations.

The vaccine should not be injected directly into a blood vessel.

Taking other medicines

Please inform your doctor or pharmacist if you are taking or have recently taken any medicines, including medicines obtained without a prescription. Enzira will not work well if you are taking medications that lower your immunity.

Pregnancy and breast-feeding

The experience from vaccinations in pregnant women is limited. If you are pregnant, ask your doctor for advice before being vaccinated. The vaccine may be given when you are breast- feeding.

Driving and using machines

Enzira is unlikely to produce an effect on your ability to drive and use machinery.

Important information about some of the ingredients of Enzira

Enzira does not contain more than 1 µg ovalbumin per dose (0.5 ml).

This medicine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially “potassium free”.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium free”.

3. HOW TO USE ENZIRA

The vaccine is administered by deep injection (subcutaneously) under your skin or into a muscle (intramuscularly) by a doctor or a nurse:

 Adults and children from 36 months: 0.5 ml  Children from 6 months to 35 months: 0.25 ml or 0.5 ml  Children who have not previously been vaccinated: a second dose is given after an interval of at least 4 weeks.

Other vaccinations can be given at the same time, provided that different injection sites are used. It should be noted that the adverse reactions may be intensified.

4. POSSIBLE SIDE EFFECTS

Like all vaccines, Enzira can have side effects, although not everybody gets them.

The following undesirable effects have been reported in clinical studies:

Common side effects (in more than 1 out of 100 but fewer than 1 out of 10 vaccinees):

 Reaction around the injection site (such as redness, pain, swelling), unusual purplish patches on the skin, hardening of skin at injection site,  Fever, feeling generally unwell, chills, tiredness,  Headache, dizziness,  Sweating,  Muscle pain or joint pain.

Most of these reactions usually disappear within 1 to 2 days without treatment.

In addition to the reactions which have been observed during clinical trials, the following adverse reactions have been reported after the introduction of trivalent influenza vaccines to the market:

 Severe stabbing or throbbing nerve pain,  Numbness or a pricking sensation in the arms or legs,  Fits,  Inflammation of the brain or spinal cord, inflammation of nerves, or Guillain-Barré syndrome, which causes extreme weakness and paralysis,  Transient blood coagulation disorder increasing the risk of bleeding or bruising (reduction in blood platelets),  Temporary swelling of glands in the neck, armpit and groin (lymph nodes),  Allergic reactions (in rare cases leading to anaphylactic shock) such as skin rash or hives, itchiness, swelling of the face, lips, tongue, throat or other parts of the body, tightness of the chest, wheezing, collapse,  Blood vessel inflammation with transient kidney involvement and little or no urine passed.

If any of the following happen, contact your doctor immediately or go to the Emergency Department at your nearest hospital:  A sudden allergic reaction (such as skin rash or hives, itchiness, swelling of the face, lips, tongue, throat or other parts of the body),  Shortness of breath, wheezing or trouble breathing,  Fits,  Little or no urine passed.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. Go to top of the page

5. HOW TO STORE ENZIRA

Keep out of the reach and sight of children. Do not use Enzira after the expiry date which is stated on the label and carton.

Store in a refrigerator (2°C to 8°C). Do not freeze.

Keep the syringe in the outer carton in order to protect from light.

6. FURTHER INFORMATION

What Enzira contains

The active substance is:

Split influenza virus*, inactivated with β-Propiolactone, containing antigens equivalent to:

A/Brisbane/59/2007 (H1N1) – like strain 15 micrograms HA** (A/Brisbane/59/2007 IVR-148)

A/Brisbane/10/2007 (H3N2) – like strain 15 micrograms HA** (A/Uruguay/716/2007 NYMC X-175C)

B/Florida/4/2006 – like strain 15 micrograms HA** (B/Florida/4/2006) per 0.5 ml dose.

* propagated in fertilised hens' eggs from healthy chicken flocks

** haemagglutinin

This vaccine complies with the WHO recommendation (Northern Hemisphere) and EU decision for the 2008/2009 season.

Other ingredients are: sodium chloride, anhydrous disodium phosphate, sodium dihydrogen phosphate dihydrate, potassium chloride, potassium dihydrogen phosphate, calcium chloride and water for injections. What Enzira looks like and contents of the pack

Enzira contains 0.5 ml of suspension for injection in a pre-filled syringe with plunger stopper (chlorobutyl rubber) with attached needle in pack sizes of 1 or 10.

The suspension is a clear to slightly opaque liquid with some sediment that resuspends upon shaking.

Marketing Authorisation Holder and Manufacturer

CSL Biotherapies GmbH Emil-von-Behring-Strasse 76 35041 Marburg Germany

Distributors:

Wyeth Pharmaceuticals Ltd. Huntercombe Lane South Taplow Maidenhead Berkshire SL6 0PH UK Wyeth Pharmaceuticals Ltd. Plaza 254 Blanchardstown Corporate Park 2 Ballycoolin Blanchardstown Dublin 15 Ireland