This information is intended for use by health professionals

1. Name of the medicinal product

Soluprick SQ Grass Pollen Phleum pratense (Timothy Grass), 10 HEP, Solution for skin prick test, 2 ml per vial

2. Qualitative and quantitative composition

Soluprick SQ Grass Pollen is a glycerinated preparation containing standardised allergen extracts dissolved in equal parts of buffered saline and sterile glycerol.

Active ingredients:

The active ingredient is a partly purified pollen allergen extract which contains the relevant allergen. The active ingredient is standardised with respect to the content of major allergen and the biological activity is controlled by a total potency assay. The potency is expressed in HEP (Histamine Equivalent in Prick testing). The biological activity of Soluprick SQ Grass Pollen is related to the reaction in the skin of an allergic patient measured relative to a histamine dihydrochloride solution.

For a full list of excipients, see section 6.1

3. Pharmaceutical form

Solution for a skin prick test (SPT)

4. Clinical particulars
4.1 Therapeutic indications

Soluprick SQ Grass Pollen is used in the diagnosis of specific IgE mediated allergic diseases.

4.2 Posology and method of administration

Dosage:

Soluprick SQ Grass Pollen 10 HEP is recommended as the optimal biological potency of the allergen when taking into account the meaning of high sensitivity related to high specificity. The potency is expressed in HEP (Histamine Equivalent in Prick testing) which is related to the allergenic activity of the allergen product in the skin of the allergic patient.

ALK Positive control (histamine dihydrochloride 10 mg/ml) is used as reference and ALK Negative control (Saline solution) is used to evaluate unspecific reactions.

When performing a SPT the amount of solution introduced into the superficial layer of the skin is extremely low, approximately 3 x 10-3   µl. (S. Dreborg, Allergy no. 10, Vol 44, 1989)

Paediatric population

Prick testing in children is already possible after the first year of life depending on the child's constitution, but in general should not be performed before the age of 4.

Skin prick test technique

- The SPT is preferably performed on the volar side of the forearm. Alternatively the test can be performed on the back of the patient.

- The skin must be dry and clean and may be disinfected with 70% alcohol.

- Each test preparation and the controls are applied in droplets on the skin in an appropriate distance from each other (a numbered tape can be used).

- The superficial layer of the skin is pierced with an ALK Lancet perpendicular to the skin through the droplet. Hold it for 1 second and draw back the lancet. For each test preparation and control a new sterile, disposable ALK Lancet is used.

The positive control is applied last.

- The droplets are wiped off with a tissue. Do not mix the preparations by sweeping!

- Start to read the reaction of the preparations after 15 minutes beginning with the positive control. A positive reaction is a pale wheal (oedema) with a red flare (erythema). To record the wheal in the patient's report: mark the contour of the wheal with a pen, stick transparent tape over the wheal. Press and transfer the tape to the report. The flare can be recorded likewise.

Size of the wheal

The mean wheal diameter of the allergen product (Da) and of the histamine control (Dh) is calculated as D = (Dl + dp )/2, where Dl is the longest diameter and dp is the diameter mid-ortogonal to Dl.

Interpretation of results

- Reactions of the allergen product can be graded in relation to the histamine control reaction. This relation is called the skin index (SI).

SI = Da/Dh

0

: negative reaction

+

: SI < 0.5

++

: 0.5 < SI < 1.0

+++

: 1.0 < SI < 2.0

++++

: 2.0 < SI

- By use of a biological standardised allergen product a mean wheal diameter ≥3 mm indicates that the patient is sensitized to the respective allergen source.

4.3 Contraindications

In extremely rare cases allergic reactions may occur and therefore, a SPT should be avoided when patients are treated with beta-blockers. Recovery from an anaphylactic reaction through the action of adrenaline may be hindered by beta-blockers since these drugs might influence an effective anti-anaphylactic treatment. Therapy with beta-blockers has to be considered an absolute contra-indication.

4.4 Special warnings and precautions for use

Any diseases seriously affecting the patient's general condition; skin lesions in the area used for the testing; dermatographism; dermatitis. Atopic eczema may hamper the reliability of the test.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant treatment with antiallergic symptomatics may affect the result of the test.

It is recommended that patients who are going to have a skin prick test performed discontinue treatment with:

Therapeutic agent

Interval between last given dose and the SPT

Short-acting antihistamines

Long-acting antihistamines

Hydroxyzine

Ketotifen

Tricyclic antidepressants

Local application of potent steroid ointment

2-3 days

8 weeks

2 weeks

2 weeks

2 weeks

2-3 weeks

Corticosteroids in doses lower than 30 mg of prednisone/prednisolone per day for up to one week do not reduce the response to skin tests.

Oral low dose glucocorticoids (doses less than 10 mg of prednisolone per day) need not to be discontinued prior to skin testing.

4.6 Pregnancy and lactation

Pregnancy is not an absolute contraindication for skin testing. Skin prick testing with Soluprick may be performed during lactation.

4.7 Effects on ability to drive and use machines

None

4.8 Undesirable effects

Undesirable effects associated with the skin-prick test can be attributed to an immunological response (local and/or systemic) provoked by the allergen (see section 5.1).

Adverse reactions are divided into groups according to the MedDRA- Convention frequencies: 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).

System Organ Class

Frequency

Adverse Drug Reaction

General disorders and administration site conditions

Very common

Application site reactions, Continuously increasing diameter of the wheal, cell shape changes (pseudopodia), diffuse swelling (delayed reaction).

Immune system disorders

Rare

Systemic allergic reactions such as rhinitis, conjunctivitis, urticaria, angioedema and asthma.

Very rare

Anaphylactic reaction/shock

Very commonly reported adverse reactions in patients tested with Soluprick are local allergic reactions at the site of application. The diameter of the wheal can continue to increase and cell shape changes (pseudopodia) may appear after the test. In some cases a delayed reaction in the form of a diffuse swelling may occur 6-24 hours after application of the skin-prick test.

In rare cases systemic allergic reaction, such as rhinitis, conjunctivitis, urticaria, angioedema or asthma may develop after the skin-prick test.

In very rare cases anaphylactic reaction/shock may develop within minutes after the skin-prick test and requires immediate treatment with adrenaline and other intensive anaphylactic treatment.

4.9 Overdose

Not relevant

5. Pharmacological properties
5.1 Pharmacodynamic properties

Soluprick SQ Grass Pollen is used for specific diagnosis by skin prick testing. The preparation is mixtures of molecules with high molecular weight compounds.

The allergenic substance of the preparation can react with the immune system of an allergic patient provided IgE antibodies to the corresponding allergen are released. An immediate allergic reaction will occur within 10-20 minutes, characterised by a wheal and flare.

This reaction is mainly caused by binding the allergen to specific IgE attached to mast cells, resulting in release of vaso-active agents like histamine. Some patients also develop a late phase reaction, i.e. a diffuse swelling and redness, starting 2 to 3 hours after the allergen piercing, peaking at 6-12 hours and disappearing within 12-24 hours.

Lymphocytes are involved in the late phase response; the exact mechanism has not yet been elucidated.

5.2 Pharmacokinetic properties

Neither the doses applied in a SPT - in terms of weight less than 0.1 µg - nor the route of administration indicate that Soluprick SQ Grass Pollen is used to acquire a clinical effect after systemic absorption.

No attempt has been made to account for the fate of the individual components.

5.3 Preclinical safety data

No toxicological studies have been performed. However, long term clinical experience confirms that non- allergic reactions are hardly of any significance.

6. Pharmaceutical particulars
6.1 List of excipients

Disodium phosphate, dihydrate

Sodium dihydrogen phosphate, dihydrate

Phenol

Sodium chloride

Glycerol

Water for Injections

The sodium content of Soluprick SQ Grass Pollen is less than 1 mmol sodium (23 mg) per dose; therefore it is essentially “sodium free”

6.2 Incompatibilities

None known. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

Shelf life of medicinal product as packaged for sale: 3 years

Shelf life after opening the container: 6 months

6.4 Special precautions for storage

Store in a refrigerator at 2-8 °C

Do not freeze. Store in original packaging in order to protect from light.

6.5 Nature and contents of container

Vial (type I glass) with a halobutyl rubber stopper and a screw cap (polypropylene).

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

ALK-Abelló A/S

Bøge Allé 6-8

DK-2970 Hørsholm

Denmark

8. Marketing authorisation number(s)

PL 10085/31

9. Date of first authorisation/renewal of the authorisation

09/07/2007

10. Date of revision of the text

13th August 2010