Pollinex Trees Extension Course 2000 SU/0.5 ml suspension for injection – patient leaflet, side effects, dosage

1. What Pollinex Trees is and what it is used for

Pollinex Trees is an allergy vaccine containing a mixture of modified extracts from Birch, Alder and Hazel pollen.

Pollinex Trees is used to treat seasonal allergic hayfever (due to tree pollen) in adults, adolescents and children from the age of 6 years who have not responded well to anti-allergy drugs. In hayfever, contact with high levels of pollen causes sneezing, blocked and runny nose and burning/watery eyes. The modified tree pollen extracts in Pollinex Trees are released slowly to reduce potential side effects.

Your treatment will begin before the start of the tree pollen season.

2. What you need to know before you use Pollinex Trees

Do not use Pollinex Trees if

• you know you have a hypersensitivity to any of the other (non active) ingredients of this medicine (listed in section 6)

• you are pregnant or think you might be pregnant

• you have lung problems such as asthma, emphysema, bronchiectasis
• you have a severe mental disorder such as depression or schizophrenia
• you have active tuberculosis of the lungs or eyes

• you have any autoimmune disease such as:

  • Rheumatoid arthritis (which affects your joints)
  • Addison’s disease (which affects the production of hormones in the body)
  • a type of hepatitis (liver disease)
  • a type of diabetes (type I)
  • Multiple sclerosis (a degenerative disease)
• you have any disorder of tyrosine metabolism including tyrosinaemia (increased blood levels of tyrosine) and alkaptonuria (causing brown colouring of the skin and eyes, damage to joints and passing black urine)
• you have any type of infection (also HIV/AIDS)
• you have had a high temperature in the last 24 hours
• you are taking beta-blockers e.g. Atenolol used in the treatment of conditions such as high blood pressure and heart problems.

Warnings and precautions

Talk to your doctor or nurse before using Pollinex Trees if:

• you suffer from any heart related medical condition. You may be able to use Pollinex Trees, but need to discuss with your doctor first. Do not eat a heavy meal immediately before you are due to have an injection.

Other medicines and Pollinex Trees

• Do not take Pollinex Trees if you are taking beta-blockers.

• Talk to your doctor, nurse or pharmacist before having Pollinex Trees if you are taking any of the following medicines:

  • Antihistamines e.g. Cetirizine used in the treatment of conditions such as hayfever, rash and swelling of the face and throat
  • Corticosteroids e.g. Beclometasone used in the treatment of conditions such as asthma, running nose and nasal congestion
  • Mast Cell Stabilisers e.g. Sodium Cromoglicate used in the treatment of conditions such as running nose, nasal congestion, asthma and itchy or sore eyes.

Tell your doctor if you are taking, have recently taken or might take any other medicines. Pollinex Trees with food, drink and alcohol

Do not eat a heavy meal immediately before an injection is due to be given. Pregnancy and breast feeding

You should not use Pollinex Trees if you are pregnant, think you might be pregnant or are breast feeding.

Driving and using machines

Occasionally the injection may cause mild drowsiness; you should not drive or use tools or machinery if you experience this symptom.

Pollinex Trees contains sodium

Pollinex Trees is essentially ‘sodium free’ since it contains less than 1 mmol sodium (23 mg) per dose.

3. How to use Pollinex Trees

Your medicine has been prescribed by and will be given to you under the supervision of a qualified doctor. They will be equipped with full facilities for cardio respiratory resuscitation to deal with any severe reaction to the vaccine.

Pollinex Trees vaccine is injected at a constant pressure under the skin. Use in children

Children under the age of 6 should not be given Pollinex Trees.

You should not be given this vaccine during the tree pollen season. The recommended doses are as follows:

Pollinex Trees Initial Course

Pollinex Trees Extension Course

(may be given after the initial course)

Main Heading :

Sub Heading :

main text :

Okomito print name

product :

course :

market :

Leaflet - Trees

PIL

General Export

material :

litho.............

digital..........

Essentra

date started :

date revised :

High Speed Opaque 50gsm

Allergy Therapeutics (UK) Limited 1.3.2-mockup-pil-uk

Vial/Syringe No./Colour

1 vial/syringe of 1 Green

1 vial/syringe of 2 Yellow

2 vials/4 Syringes of 3 Red

Concentration (Standardised Units (SU)/0.5 ml)

Vial/Syringe No. and Colour

Vial/Syringe No. 1 (Green)

Vial/Syringe No. 2 (Yellow)

Vial/Syringe No. 3 (Red)

Recommended dosage

300 SU – 0.5 ml

800 SU – 0.5 ml

2000 SU – 0.5 ml

1Green

2Yellow

3Red

DOSAGE PLAN:

POLLINEX Trees and POLLINEX Trees Extension Course

Apply Patient Label Here

(or enter patient details)

Patient Name:

Address:

Date of Birth:

Doctor:

Hospital No.:

Treatment Course

Interval between each injection should be 7-14 days

Vial/Syringe

Number

Recommended

Dosage in ml

Administered

Dosage in ml Date Signature Comments

3Red

Vial/Syringe

Number

Recommended

Dosage in ml

Administered

Dosage in ml Date Signature Comments Interval

2 weeks* since

last injection

from treatment

course

0.5 ml

Extension Course

*If the pollen season is imminent, the interval between each injection may be reduced to 1 week

Technical User Leaflet

POLLINEX

Trees

1. 1. NAME OF THE MEDICINAL PRODUCT

POLLINEX Trees, 300, 800 and 2000 Standardised Units (SU)/0.5 ml, suspension for injection

POLLINEX Trees Extension Course, 2000 Standardised Units (SU)/0.5 ml, suspension for injection

1. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

POLLINEX Trees treatment comprises a series of 4 pre-filled vials/6 pre-filled syringes in the following concentrations:

POLLINEX Trees contains equal proportions of 3 selectively purified allergen extracts of pollen from the following trees:

Birch (Betula Spp)

Alder (Alnus Spp)

Hazel (Corylus Spp)

The allergens have been converted into allergoids by treatment with glutaraldehyde and are adsorbed onto L-tyrosine. The allergen extracts are characterised and standardised through immunological and biochemical methods to ensure batch-to-batch consistent allergen content and allergenic potency. Major allergens are measured in selected extracts. Standardisation is reflected by the assignment of Standardised Units (SU).

For the full list of excipients, see section 6.1.

1. 3. PHARMACEUTICAL FORM

Suspension for injection

A white opaque suspension

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of seasonal allergic hayfever due to tree pollen in adults, adolescents and children from the age of 6 years who have failed to respond adequately to anti-allergy drugs.

The diagnosis should be based on the careful consideration of the patient's history and allergy tests, preferably skin tests.

4.2 Posology and method of administration

Posology

POLLINEX Trees is presented in three multi-dose 3 ml vials or three unit dose 1 ml syringes. Each vial/syringe is prefilled with 1.0 ml/0.5 ml vaccine respectively in graded concentrations as follows:

The injections should be given at intervals of 7-14 days. Treatment is to be initiated with 0.5 ml of vial/syringe No. 1, followed 7-14 days later by 0.5 ml of vial/syringe No. 2 and finally 7-14 days later by 0.5 ml of vial/syringe No. 3, in accordance with the dosage regimen above.

The above dosage regimen is suitable for most patients in whom it is indicated. However, if the patient is particularly sensitive, then the dosage and the progression from dose to dose, should be modified according to the clinician’s discretion.

The maximum dose of 0.5 ml must not be exceeded.

The course should be completed before the onset of the tree pollen season. Do not use during the tree pollen season.

POLLINEX Trees can be followed by the pre-seasonal Extension Course included in this pack for continued clinical improvement.

The Extension Course consists of three injections of the maximum dose of 2000 SU/0.5 ml. If the maximum dose is not tolerated, treatment can take place at a lower dose. The first injection of 0.5 ml should be given about 14 days after the last injection of POLLINEX Trees. Subsequent injections should then be given at intervals of 2-4 weeks. If the season is imminent, the interval can be reduced to 1 week.

It is recommended that the allergy vaccine should be given in each of three successive years.

Paediatric population

For children from the age of 6 years and adolescents, the same posology regime as adults is recommended.

POLLINEX Trees should not be used in children under 6 years of age.

Method of administration

For subcutaneous injection (see section 6.6 for instructions on handling).

It should be administered at a constant pressure by subcutaneous injection to the middle third of the lateral posterior aspect of the upper arm. The injection sites should be alternated between arms, e.g. 1st and 3rd injection in the right arm and 2nd injection in the left arm. Repeated injections at one injection site should be avoided. Do not inject into a blood vessel or intramuscularly. The patient should be instructed not to rub the injection site.

4.3 Contraindications

Contraindicated in patients with asthma because they are more likely to develop life threatening reactions.

Patients should not be given an allergy vaccine if they have febrile infections or inflammation of the respiratory tract; irreversible secondary changes of the reactive organs (emphysema, bronchiectasis etc); severe chronic and inflammatory diseases, immunopathological conditions, active tuberculosis of the lung and eyes, severe mental disorders or are receiving beta-blocker therapy.

Hyposensitisation injections should not be given to patients with systemic or local infection or who have suffered from a febrile condition in the 24 hours preceding the intended dose or if they have immunodeficiency or an autoimmune disease.

If tyrosine metabolism is disturbed, especially in the case of tyrosinaemia and alkaptonuria, or if there is a known hypersensitivity to any of the excipients listed in section 6.1, POLLINEX Trees should not be used.

If the patient is pregnant/discover they become pregnant whilst receiving treatment POLLINEX Trees should not be started or continued during pregnancy as pregnancy may change the patient's sensitisation level to a degree that cannot be foreseen. Please refer to section 4.6 Pregnancy and lactation.

4.4 Special warnings and precautions for use

The individual tolerated dose should not be exceeded.

Treatment of patients should only be carried out where full facilities for cardio-respiratory resuscitation are immediately available.

Adrenaline (Epinephrine) Injection should always be kept at hand when giving any allergen specific immunotherapy.

Patients should be kept under observation for the first 60 minutes after each injection. This period should be extended if even mild symptoms or signs of hypersensitivity develop and patients should be maintained under observation until these have completely resolved. A severe and prolonged adverse reaction may necessitate hospital admission.

Anaphylactic shock

As with any specific immunotherapy there is a risk of anaphylactic shock.

Warning symptoms:

Tingling, itching and burning sensations on the tongue, in the mouth, throat or particularly on the palms and soles. This may be immediately followed by shock with cyanosis, hypotension, tachycardia, bronchospasm and unconsciousness.

Further clinical signs are: anxiety, restlessness, urticaria, dizziness, laryngeal oedema with dyspnoea, nausea and vomiting, respiratory and cardiac arrest.

Severe and potentially life-threatening reactions require fast and effective emergency treatment.

The treatment of allergic reactions is based on current medical guidelines.

In the event of simultaneous vaccination against viral or bacterial pathogens, there should be an interval of at least one week between the last injection of POLLINEX Trees and the day of vaccination provided all side effects (local or systemic) have completely disappeared. The next dose of POLLINEX Trees may be administered two weeks after the vaccination, provided that all side effects to the vaccination have completely disappeared, using half of the last dose administered.

Afterwards, this amount can be increased according to the dosage chart at intervals of 7-14 days.

Use with caution in patients with cardiovascular deficiency.

Patients should be warned not to eat a heavy meal immediately before an injection is due to be given.

Injections should be given at a constant pressure by the subcutaneous route. Do not inject into a blood vessel or intramuscularly. Do not rub the site of injection.

The patient should not take any strenuous physical exercise for 12 hours following the injection.

All patients should be advised to contact the doctor immediately in the event of an adverse reaction.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant therapy with symptomatic anti-allergic agents (e.g. antihistamines, corticosteroids, mast cell stabilisers) may affect the tolerance level of the patient. A reduction of the dose after discontinuing treatment with these symptomatic preparations may be required.

During hyposensitisation, exposure to the causal allergens and allergens cross-reacting with them is to be avoided as far as possible.

POLLINEX Trees is contraindicated in those receiving Beta-blockers, please refer to section 4.3.

4.6 Fertility, pregnancy and lactation

The use of POLLINEX Trees is contraindicated in pregnancy (see section 4.3).

4.7 Effects on ability to drive and use machines

Occasionally the injection may cause mild drowsiness; the patient should be instructed not to drive or operate machinery if this is the case.

4.8 Undesirable effects

If the injection intervals and dosage regimens are followed exactly and the dose is individually increased in an appropriate manner, allergic side reactions to treatment with the allergy vaccine are rare. They are usually mild but local and/or systemic reactions must be anticipated, in which case the treatment must be immediately discontinued. For these reasons an emergency kit should be immediately available. As a precautionary measure, each patient must be kept under observation for at least 60 minutes after injections, after which time a medical assessment is made.

Reactions:

Local - Such as swelling or irritation. These may require symptomatic treatment if they are severe or persist. In extremely rare cases, granuloma may be observed, especially if the injection was too superficial.

Systemic:

Mild - Such as rhinitis or urticaria.

Fatigue occasionally occurs after injection of the vaccine.

Atopic eczema may be exacerbated by hyposensitisation.

Moderate-Severe - Such as severe wheezing or bronchospasm.

Description of selected adverse reactions

Anaphylactic reactions/anaphylactic shock

Severe anaphylactic reactions or anaphylactic shock have been reported in individual cases. Anaphylactic shock can develop minutes after administration of any allergy immunotherapy, often before a local reaction has appeared (see section 4.4).

Typical warning symptoms of anaphylactic shock are described in section 4.4.

In rare cases, adverse reactions may occur even a few hours after the hyposensitisation injection, in which case the patient should inform their attending doctor before the next injection. When in doubt especially after the appearance of systemic reactions the patients should seek medical advice/treatment immediately.

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 Yellow Card Scheme website: www.mhra.gov.uk/yellowcard

4.9 Overdose

Symptoms:

If a patient receives an overdose of an allergy vaccine, the likelihood of an adverse reaction is increased.

Reactions are characterised by symptoms ranging from slight swelling or irritation at the site of injection to anaphylaxis.

Management:

1. 1) See 4.8 Undesirable effects.
2. 2) The usual precautions should be followed i.e.

Patients should be kept under medical observation for at least 60 minutes after each injection.

The patient should not take any strenuous physical exercise for 12 hours following the injection.

All patients should be advised to contact the doctor immediately in the event of a reaction.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: allergens, ATC Classification: V01A A05.

Immunotherapy with POLLINEX Trees is recommended for patients who are sensitive to specific pollens. The effectiveness of immunotherapy in reducing symptoms has been established by controlled, blinded studies.

The specific pollen allergens incorporated in POLLINEX Trees have been modified by glutaraldehyde treatment and adsorbed onto tyrosine with the result that allergenicity is reduced (thus increasing tolerance) while maintaining immunogenicity (related to efficacy).

Although the immunological events are not clearly understood, the production of antigen specific IgG antibody, suppression of specific IgE and decreased mediator (histamine) release from basophils are important factors.

The therapeutic effects of specific pollens immunotherapy are allergen-specific and dose dependent.

5.2 Pharmacokinetic properties

POLLINEX Trees contains glutaraldehyde-modified extracts of specific pollens adsorbed onto L-tyrosine. The adsorbate L-tyrosine is a natural amino acid, which is metabolised in the body and ensures that the active material (the allergoid) is released more slowly. This results in a prolonged and efficient desensitising effect and improves tolerance.

5.3 Preclinical safety data

No further information of relevance.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

L-Tyrosine

Liquefied Phenol

Sodium Chloride

Disodium Phosphate Dodecahydrate

Sodium Dihydrogen Phosphate Dihydrate

Glycerol

Water for Injections

6.2 Incompatibilities

Not Applicable.

6.3 Shelf-life

3 years.

6.4 Special precautions for storage

Store in a refrigerator (2°C - 8°C). Do not freeze. Remove from refrigerator 2-3 hours before use.

6.5 Nature and contents of container

The vials are 3.0 ml vials made from clear neutral glass (Type I, Ph. Eur.) fitted with a butyl bung, aluminium seals and coloured flip tops.

The pre-filled syringes are 1.0 ml syringes made from clear neutral glass (Type 1, Ph. Eur.) with a polypropylene plunger rod and a butyl plunger.

A pack of POLLINEX Trees contains 3 multi-dose vials each containing 1.0 ml suspension or 3 unit dose syringes containing 0.5 ml suspension in graded concentrations as follows:

Vial/Syringe No. 1. (Green) with 300 SU/0.5 ml

Vial/Syringe No. 2. (Yellow) with 800 SU/0.5 ml

Vial/Syringe No. 3. (Red) with 2000 SU/0.5 ml

The included Extension Course consists of one multi-dose vial containing 1.5 ml of suspension or 3 additional unit dose pre-filled syringes containing 0.5 ml of suspension as follows:

Vial/Syringe No. 3. (Red) with 2000 SU/0.5 ml

Packs containing the product in vials also contain empty syringes and needles suitable for dispensing the product.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The pack should be removed from the refrigerator at least 2-3 hours before use and warmed to room temperature.

POLLINEX Trees is a white opaque suspension. During storage a white deposit with colourless supernatant may form. Therefore, before use it is important to ensure that the vial/syringe is thoroughly shaken to ensure that all of the sediment is evenly re-suspended.

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

1. 7. MARKETING AUTHORISATION HOLDER

Allergy Therapeutics (UK) Ltd., Dominion Way, Worthing, West Sussex, BN14 8SA, United Kingdom.

1. 8. MARKETING AUTHORISATION NUMBER

PL 17087/0007

PL 17087/0008

1. 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 27 August 1998

Date of latest renewal: 26 April 2005

1. 10. DATE OF (PARTIAL) REVISION OF TEXT

0.5 ml

0.5 ml

0.5 ml

0.5 ml

0.5 ml

2-4 weeks*

2-4 weeks*

1 Colour

(does not print)

Allergy Therapeutics

Leaflet

Pollinex Trees

v2

Okomito family

Vial/Syringe No./Colour

1 vial/syringe of 1 Green

1 vial/syringe of 2 Yellow

2 vials/4 Syringes of 3 Red

Concentration (Standardised Units (SU)/0.5 ml)

Vial/Syringe No. and Colour

Vial/Syringe No. 1 (Green)

Vial/Syringe No. 2 (Yellow)

Vial/Syringe No. 3 (Red)

Recommended dosage

300 SU – 0.5 ml

800 SU – 0.5 ml

2000 SU – 0.5 ml

1Green

2Yellow

3Red

DOSAGE PLAN:

POLLINEX Trees and POLLINEX Trees Extension Course

Apply Patient Label Here

(or enter patient details)

Patient Name:

Address:

Date of Birth:

Doctor:

Hospital No.:

Treatment Course

Interval between each injection should be 7-14 days

Vial/Syringe

Number

Recommended

Dosage in ml

Administered

Dosage in ml Date Signature Comments

3Red

Vial/Syringe

Number

Recommended

Dosage in ml

Administered

Dosage in ml Date Signature Comments Interval

2 weeks* since

last injection

from treatment

course

0.5 ml

Extension Course

*If the pollen season is imminent, the interval between each injection may be reduced to 1 week

Technical User Leaflet

POLLINEX

Trees

1. 1. NAME OF THE MEDICINAL PRODUCT

POLLINEX Trees, 300, 800 and 2000 Standardised Units (SU)/0.5 ml, suspension for injection

POLLINEX Trees Extension Course, 2000 Standardised Units (SU)/0.5 ml, suspension for injection

1. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

POLLINEX Trees treatment comprises a series of 4 pre-filled vials/6 pre-filled syringes in the following concentrations:

POLLINEX Trees contains equal proportions of 3 selectively purified allergen extracts of pollen from the following trees:

Birch (Betula Spp)

Alder (Alnus Spp)

Hazel (Corylus Spp)

The allergens have been converted into allergoids by treatment with glutaraldehyde and are adsorbed onto L-tyrosine. The allergen extracts are characterised and standardised through immunological and biochemical methods to ensure batch-to-batch consistent allergen content and allergenic potency. Major allergens are measured in selected extracts. Standardisation is reflected by the assignment of Standardised Units (SU).

For the full list of excipients, see section 6.1.

1. 3. PHARMACEUTICAL FORM

Suspension for injection

A white opaque suspension

1. 4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of seasonal allergic hayfever due to tree pollen in adults, adolescents and children from the age of 6 years who have failed to respond adequately to anti-allergy drugs.

The diagnosis should be based on the careful consideration of the patient's history and allergy tests, preferably skin tests.

4.2 Posology and method of administration

Posology

POLLINEX Trees is presented in three multi-dose 3 ml vials or three unit dose 1 ml syringes. Each vial/syringe is prefilled with 1.0 ml/0.5 ml vaccine respectively in graded concentrations as follows:

The injections should be given at intervals of 7-14 days. Treatment is to be initiated with 0.5 ml of vial/syringe No. 1, followed 7-14 days later by 0.5 ml of vial/syringe No. 2 and finally 7-14 days later by 0.5 ml of vial/syringe No. 3, in accordance with the dosage regimen above.

The above dosage regimen is suitable for most patients in whom it is indicated. However, if the patient is particularly sensitive, then the dosage and the progression from dose to dose, should be modified according to the clinician’s discretion.

The maximum dose of 0.5 ml must not be exceeded.

The course should be completed before the onset of the tree pollen season. Do not use during the tree pollen season.

POLLINEX Trees can be followed by the pre-seasonal Extension Course included in this pack for continued clinical improvement.

The Extension Course consists of three injections of the maximum dose of 2000 SU/0.5 ml. If the maximum dose is not tolerated, treatment can take place at a lower dose. The first injection of 0.5 ml should be given about 14 days after the last injection of POLLINEX Trees. Subsequent injections should then be given at intervals of 2-4 weeks. If the season is imminent, the interval can be reduced to 1 week.

It is recommended that the allergy vaccine should be given in each of three successive years.

Paediatric population

For children from the age of 6 years and adolescents, the same posology regime as adults is recommended.

POLLINEX Trees should not be used in children under 6 years of age.

Method of administration

For subcutaneous injection (see section 6.6 for instructions on handling).

It should be administered at a constant pressure by subcutaneous injection to the middle third of the lateral posterior aspect of the upper arm. The injection sites should be alternated between arms, e.g. 1st and 3rd injection in the right arm and 2nd injection in the left arm. Repeated injections at one injection site should be avoided. Do not inject into a blood vessel or intramuscularly. The patient should be instructed not to rub the injection site.

4.3 Contraindications

Contraindicated in patients with asthma because they are more likely to develop life threatening reactions.

Patients should not be given an allergy vaccine if they have febrile infections or inflammation of the respiratory tract; irreversible secondary changes of the reactive organs (emphysema, bronchiectasis etc); severe chronic and inflammatory diseases, immunopathological conditions, active tuberculosis of the lung and eyes, severe mental disorders or are receiving beta-blocker therapy.

Hyposensitisation injections should not be given to patients with systemic or local infection or who have suffered from a febrile condition in the 24 hours preceding the intended dose or if they have immunodeficiency or an autoimmune disease.

If tyrosine metabolism is disturbed, especially in the case of tyrosinaemia and alkaptonuria, or if there is a known hypersensitivity to any of the excipients listed in section 6.1, POLLINEX Trees should not be used.

If the patient is pregnant/discover they become pregnant whilst receiving treatment POLLINEX Trees should not be started or continued during pregnancy as pregnancy may change the patient's sensitisation level to a degree that cannot be foreseen. Please refer to section 4.6 Pregnancy and lactation.

4.4 Special warnings and precautions for use

The individual tolerated dose should not be exceeded.

Treatment of patients should only be carried out where full facilities for cardio-respiratory resuscitation are immediately available.

Adrenaline (Epinephrine) Injection should always be kept at hand when giving any allergen specific immunotherapy.

Patients should be kept under observation for the first 60 minutes after each injection. This period should be extended if even mild symptoms or signs of hypersensitivity develop and patients should be maintained under observation until these have completely resolved. A severe and prolonged adverse reaction may necessitate hospital admission.

Anaphylactic shock

As with any specific immunotherapy there is a risk of anaphylactic shock.

Warning symptoms:

Tingling, itching and burning sensations on the tongue, in the mouth, throat or particularly on the palms and soles. This may be immediately followed by shock with cyanosis, hypotension, tachycardia, bronchospasm and unconsciousness.

Further clinical signs are: anxiety, restlessness, urticaria, dizziness, laryngeal oedema with dyspnoea, nausea and vomiting, respiratory and cardiac arrest.

Severe and potentially life-threatening reactions require fast and effective emergency treatment.

The treatment of allergic reactions is based on current medical guidelines.

In the event of simultaneous vaccination against viral or bacterial pathogens, there should be an interval of at least one week between the last injection of POLLINEX Trees and the day of vaccination provided all side effects (local or systemic) have completely disappeared. The next dose of POLLINEX Trees may be administered two weeks after the vaccination, provided that all side effects to the vaccination have completely disappeared, using half of the last dose administered.

Afterwards, this amount can be increased according to the dosage chart at intervals of 7-14 days.

Use with caution in patients with cardiovascular deficiency.

Patients should be warned not to eat a heavy meal immediately before an injection is due to be given.

Injections should be given at a constant pressure by the subcutaneous route. Do not inject into a blood vessel or intramuscularly. Do not rub the site of injection.

The patient should not take any strenuous physical exercise for 12 hours following the injection.

All patients should be advised to contact the doctor immediately in the event of an adverse reaction.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant therapy with symptomatic anti-allergic agents (e.g. antihistamines, corticosteroids, mast cell stabilisers) may affect the tolerance level of the patient. A reduction of the dose after discontinuing treatment with these symptomatic preparations may be required.

During hyposensitisation, exposure to the causal allergens and allergens cross-reacting with them is to be avoided as far as possible.

POLLINEX Trees is contraindicated in those receiving Beta-blockers, please refer to section 4.3.

4.6 Fertility, pregnancy and lactation

The use of POLLINEX Trees is contraindicated in pregnancy (see section 4.3).

4.7 Effects on ability to drive and use machines

Occasionally the injection may cause mild drowsiness; the patient should be instructed not to drive or operate machinery if this is the case.

4.8 Undesirable effects

If the injection intervals and dosage regimens are followed exactly and the dose is individually increased in an appropriate manner, allergic side reactions to treatment with the allergy vaccine are rare. They are usually mild but local and/or systemic reactions must be anticipated, in which case the treatment must be immediately discontinued. For these reasons an emergency kit should be immediately available. As a precautionary measure, each patient must be kept under observation for at least 60 minutes after injections, after which time a medical assessment is made.

Reactions:

Local - Such as swelling or irritation. These may require symptomatic treatment if they are severe or persist. In extremely rare cases, granuloma may be observed, especially if the injection was too superficial.

Systemic:

Mild - Such as rhinitis or urticaria.

Fatigue occasionally occurs after injection of the vaccine.

Atopic eczema may be exacerbated by hyposensitisation.

Moderate-Severe - Such as severe wheezing or bronchospasm.

Description of selected adverse reactions

Anaphylactic reactions/anaphylactic shock

Severe anaphylactic reactions or anaphylactic shock have been reported in individual cases. Anaphylactic shock can develop minutes after administration of any allergy immunotherapy, often before a local reaction has appeared (see section 4.4).

Typical warning symptoms of anaphylactic shock are described in section 4.4.

In rare cases, adverse reactions may occur even a few hours after the hyposensitisation injection, in which case the patient should inform their attending doctor before the next injection. When in doubt especially after the appearance of systemic reactions the patients should seek medical advice/treatment immediately.

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 Yellow Card Scheme website: www.mhra.gov.uk/yellowcard

4.9 Overdose

Symptoms:

If a patient receives an overdose of an allergy vaccine, the likelihood of an adverse reaction is increased.

Reactions are characterised by symptoms ranging from slight swelling or irritation at the site of injection to anaphylaxis.

Management:

1. 1) See 4.8 Undesirable effects.
2. 2) The usual precautions should be followed i.e.

Patients should be kept under medical observation for at least 60 minutes after each injection.

The patient should not take any strenuous physical exercise for 12 hours following the injection.

All patients should be advised to contact the doctor immediately in the event of a reaction.

1. 5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: allergens, ATC Classification: V01A A05.

Immunotherapy with POLLINEX Trees is recommended for patients who are sensitive to specific pollens. The effectiveness of immunotherapy in reducing symptoms has been established by controlled, blinded studies.

The specific pollen allergens incorporated in POLLINEX Trees have been modified by glutaraldehyde treatment and adsorbed onto tyrosine with the result that allergenicity is reduced (thus increasing tolerance) while maintaining immunogenicity (related to efficacy).

Although the immunological events are not clearly understood, the production of antigen specific IgG antibody, suppression of specific IgE and decreased mediator (histamine) release from basophils are important factors.

The therapeutic effects of specific pollens immunotherapy are allergen-specific and dose dependent.

5.2 Pharmacokinetic properties

POLLINEX Trees contains glutaraldehyde-modified extracts of specific pollens adsorbed onto L-tyrosine. The adsorbate L-tyrosine is a natural amino acid, which is metabolised in the body and ensures that the active material (the allergoid) is released more slowly. This results in a prolonged and efficient desensitising effect and improves tolerance.

5.3 Preclinical safety data

No further information of relevance.

1. 6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

L-Tyrosine

Liquefied Phenol

Sodium Chloride

Disodium Phosphate Dodecahydrate

Sodium Dihydrogen Phosphate Dihydrate

Glycerol

Water for Injections

6.2 Incompatibilities

Not Applicable.

6.3 Shelf-life

3 years.

6.4 Special precautions for storage

Store in a refrigerator (2°C - 8°C). Do not freeze. Remove from refrigerator 2-3 hours before use.

6.5 Nature and contents of container

The vials are 3.0 ml vials made from clear neutral glass (Type I, Ph. Eur.) fitted with a butyl bung, aluminium seals and coloured flip tops.

The pre-filled syringes are 1.0 ml syringes made from clear neutral glass (Type 1, Ph. Eur.) with a polypropylene plunger rod and a butyl plunger.

A pack of POLLINEX Trees contains 3 multi-dose vials each containing 1.0 ml suspension or 3 unit dose syringes containing 0.5 ml suspension in graded concentrations as follows:

Vial/Syringe No. 1. (Green) with 300 SU/0.5 ml

Vial/Syringe No. 2. (Yellow) with 800 SU/0.5 ml

Vial/Syringe No. 3. (Red) with 2000 SU/0.5 ml

The included Extension Course consists of one multi-dose vial containing 1.5 ml of suspension or 3 additional unit dose pre-filled syringes containing 0.5 ml of suspension as follows:

Vial/Syringe No. 3. (Red) with 2000 SU/0.5 ml

Packs containing the product in vials also contain empty syringes and needles suitable for dispensing the product.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The pack should be removed from the refrigerator at least 2-3 hours before use and warmed to room temperature.

POLLINEX Trees is a white opaque suspension. During storage a white deposit with colourless supernatant may form. Therefore, before use it is important to ensure that the vial/syringe is thoroughly shaken to ensure that all of the sediment is evenly re-suspended.

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

1. 7. MARKETING AUTHORISATION HOLDER

Allergy Therapeutics (UK) Ltd., Dominion Way, Worthing, West Sussex, BN14 8SA, United Kingdom.

1. 8. MARKETING AUTHORISATION NUMBER

PL 17087/0007

PL 17087/0008

1. 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 27 August 1998

Date of latest renewal: 26 April 2005

1. 10. DATE OF (PARTIAL) REVISION OF TEXT

0.5 ml

0.5 ml

0.5 ml

0.5 ml

0.5 ml

2-4 weeks*

2-4 weeks*

1 Colour

(does not print)

Allergy Therapeutics

Leaflet

Pollinex Trees

v2

Okomito family