Solutions for provocation tests allergopharma

PACKAGE LEAFLET: INFORMATION FOR THE USER

Allergopharma Provocation Test Solutions
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.
Keep this leaflet as you may need to read it again.
If you have any questions, please consult your doctor or pharmacist.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor. See section 4.
Leaflet contents:

1. What Allergopharma Provocation Test Solutions are and what they are used for
2. Important information before using Allergopharma Provocation Test Solutions
3. How to use Allergopharma Provocation Test Solutions
4. Possible side effects
5. How to store Allergopharma Provocation Test Solutions
6. Contents of the pack and other information

1. What Allergopharma Provocation Test Solutions are and what they are used for

Provocation tests are used as an auxiliary tool in the diagnosis of allergic diseases. The allergen contained in the test solution reacts with allergen-specific IgE antibodies present in the patient's mucous membranes. This reaction leads to the release of mediators, particularly histamine, from mast cells, resulting in inflammatory response, increased mucus secretion, and smooth muscle contraction.
During a provocation test, increasing doses of the allergen are administered intranasally or bronchially.
The occurrence of an allergic reaction confirms the clinical relevance of the specific allergen and may be significant, for example, in selecting patients for and monitoring the effects of specific immunotherapy.
Allergopharma Provocation Test Solutions are used in the diagnosis of IgE-dependent allergic diseases (type I according to Gell and Coombs classification) by provocation of the target organ with a positively identified allergen from skin prick testing.

2. Information before using Allergopharma Provocation Test Solutions

Allergopharma
When not to use Allergopharma Provocation Test Solutions
Do not use Allergopharma Provocation Test Solutions if the following conditions are present:

• significant diseases substantially impairing general health,
• high degree of sensitization (based on medical history and skin test reactions), because this increases the risk of severe allergic reaction,
• concomitant treatment with beta-adrenergic receptor blockers and angiotensin-converting enzyme inhibitors, because they reduce the effectiveness of adrenaline,
• pregnancy – due to the risk of anaphylactic reactions, which may lead to fetal hypoxia,
• hypersensitivity (allergy) to any of the excipients.

Do not use Allergopharma Provocation Test Solutions for bronchial provocation tests if the following conditions are present:

• significant impairment of lung function, because triggering an allergic reaction may lead to respiratory failure,
• additional risk associated with unavoidable concomitant medication (e.g. cholinergic drugs),
• pronounced bronchial hyperreactivity, because an allergic reaction may provoke severe bronchospasm.

Do not use Allergopharma Provocation Test Solutions for nasal provocation tests if the following conditions are present:

• acute inflammatory diseases of the nose and sinuses, because this increases the risk of severe allergic reaction,
• acute immediate-type allergic reactions affecting other effector organs.

Warnings and precautions
Before starting the use of Allergopharma Provocation Test Solutions, the following should be considered:

• Discuss with the physician the degree of sensitization. In highly sensitized patients, children, and in cases of particularly potent allergens, a higher dilution of the allergen solution with physiological saline is recommended for nasal provocation tests (e.g. 1:10), or a greater number of dilutions (e.g. 1:1000000, 1:10000000) should be used in bronchial provocation tests. Prior to such testing, a fast-acting bronchodilator should be prepared for inhalation administration.
• Pay attention to inhalation technique. During nasal provocation, deep inhalation of the allergen should be avoided. Breath should be held during allergen administration, followed by exhalation through the nose.
• Inform the physician about concomitant medical conditions such as hypertension, ischemic heart disease, cardiac arrhythmias, and hyperthyroidism, as adrenaline – recommended in case of adverse reactions to Allergopharma Provocation Test Solutions – may be contraindicated in these conditions.

All provocation tests, both nasal and bronchial, should be performed during periods of absence or minimal severity of allergic symptoms.

Children and adolescents
Depending on the patient's condition, bronchial provocation testing may be performed from the age of 6 years, and nasal provocation testing from the age of 3 years.

Allergopharma Provocation Test Solutions and other medicines
Inform the physician about all medicines recently taken, including those available without a prescription.
Avoid administering drugs affecting the effector organ undergoing provocation. Antihistamines, steroids, mast cell stabilizers, and drugs with weak antihistaminic effects may lead to false-negative results.
Whenever possible, these medications should be discontinued before testing for a period corresponding to their duration of action as specified by the manufacturer.

Pregnancy, breastfeeding, and fertility
There is insufficient experience regarding use during pregnancy and breastfeeding.
Provocation tests should not be performed during pregnancy (due to the risk of anaphylactic reactions).
Performing a provocation test probably poses no risk to a breastfed infant; however, in each case, the risks and benefits of performing the test should be individually assessed.

Driving and operating machinery
The effect of provocation testing on driving and operating machinery is unknown.

3. How to use Allergopharma Provocation Test Solutions

Recommended dose
Bronchial provocation test
Depending on the type of equipment used, 1–2 mL of solution is introduced into the nebulizer, from which only small particle doses are inhaled each time. The recommended concentration of allergen depends on: the type of allergen, the degree of patient sensitization, and bronchial hyperreactivity. Provocation starts with the lowest concentration and is repeated with progressively higher concentrations until a positive reaction occurs or until the undiluted solution is administered. Recommended dilutions of the test solution with physiological saline:

1. Provocation: 1:10,000 (or even lower concentration in highly sensitized patients)
2. Provocation: 1:1,000
3. Provocation: 1:100
4. Provocation: 1:10
5. Provocation: undiluted test solution

Nasal provocation test

• "Spray" method: Administer 0.04–0.05 mL of test solution using a spray device.
• "Tuberculin syringe" method: Administer 0.05 mL (2 drops of test solution) using a tuberculin syringe onto the surface of the lower nasal turbinate.

Administration method
To dissolve the powder, draw 5 mL of solvent using a sterile needle and syringe and inject it into the vial containing the powder. Mix thoroughly until the powder is completely dissolved. The resulting solution is ready for testing. The date of reconstitution must be recorded on the label. Dilutions of the test solution are prepared by adding physiological saline.
For the nasal provocation test using the "spray" method, remove the stopper and cap, then attach the spray nozzle (with plastic protector). Only single allergens are tested (mixtures such as grass or grass/cereals are considered single allergens).

Bronchial provocation test
One allergen should be administered per day. Increasing allergen concentrations should be applied at intervals of 2–3 hours until a positive test result is achieved or until no reaction occurs with the undiluted solution. Due to the physiological circadian rhythm, provocation should be performed in the morning hours.
Prior to the actual provocation, the patient should inhale phenol-preserved 0.4% physiological saline (negative control) to establish baseline values for the test and to detect non-specific reactions. Subsequently, the test solution is nebulized. Inhalation must be immediately discontinued upon the appearance of the first mild clinical symptoms. Pulmonary function parameters are usually measured immediately after inhalation ends, and again at 10 and 20 minutes post-inhalation. A late-phase reaction may occur up to 24 hours after inhalation of the test solution, with maximum intensity around 4–12 hours. During this period, medical supervision and access to medical evaluation must be ensured for the patient.

Nasal provocation test
No more than two allergens may be administered in one day, although each allergen may be tested at several concentrations. A second allergen may only be tested if the reaction to the first allergen was not stronger than the negative control reaction. Each test must be preceded by a control test with phenol-preserved 0.4% physiological saline (negative control) to detect non-specific reactions and to establish baseline values for further measurements. After identifying the nostril with better patency and performing the initial rhinomanometric measurement, the negative control solution is administered to that side. After 15 minutes, a control measurement is performed on the same side. If no significant change in nasal patency is observed in the control measurement, provocation with the allergen is performed on the same side. After 15 minutes, the effect is recorded by measurement or assessment of symptom severity. In case of a negative reaction, the measurement is repeated after 30 minutes. For house dust mite and mold allergens, an additional measurement is taken after 45 minutes in case of a negative reaction. The nasal provocation test can be evaluated both based on symptom severity (e.g. nasal blockage, amount of discharge, irritation, symptoms in other organs) and rhinomanometrically (demonstration of nasal blockage by measuring nasal resistance). The provocation test is considered positive if, after allergen provocation, there is a decrease in airflow of at least 40% compared to the control test. If the test result is negative or inconclusive, the nasal provocation with the same allergen may be repeated the following day.

"Spray" method – After dissolving the powder, screw on the spray nozzle and attach the nasal applicator. A new nasal applicator must be used for each patient and for each allergen. Pump several times to ensure the liquid reaches the dosing mechanism. Ask the patient to blow their nose, tilt their head backward, take a deep breath, and then hold their breath. By pressing the nasal applicator, the control or test solution is sprayed onto the surface of the lower nasal turbinate. The patient should then perform a rapid exhalation through the nose. After completion of the test, remove the dosing nozzle and replace the protective cap.

"Tuberculin syringe" method – Using a tuberculin syringe, apply the test or control solution onto the surface of the lower nasal turbinate.

In case of administration of a higher dose of Allergopharma Provocation Test Solutions than recommended, exacerbation of allergic symptoms may occur (see section 4. Possible adverse effects). Symptomatic treatment (e.g. antihistamines, bronchodilators) should be administered and medical advice should be sought immediately.

4. Possible adverse reactions

Bronchial provocation test
The bronchial provocation test may provoke an asthma attack; in such case, a bronchodilator inhalation should be administered. Treatment for severe asthma attack must be available at the test site.
Nasal provocation test
Excessive mucosal reaction in the nose can be managed by administering local antihistamines or vasoconstrictive nasal drops. In rare cases, distant symptoms may occur (conjunctival reactions, palate itching, cough).
In extreme cases, provocation tests may induce a severe allergic reaction (anaphylactic shock). Anaphylactic shock may develop within seconds or minutes after allergen administration. Typical early symptoms include itching and a sensation of warmth in the tongue, under the tongue, and in the throat, as well as itching of the palms and soles.
An emergency anaphylaxis kit and an adrenaline-filled syringe must always be prepared and readily available during testing.
In managing anaphylactic reactions, follow the enclosed protocol "Management of emergencies during provocation tests".
After administration of the test solution, the patient must be monitored for at least 30 minutes, and then examined by a physician.
It should be noted that adverse reactions may occur several hours after allergen administration (very rarely). In cases causing concern, especially in the event of systemic reactions, the patient should contact a physician immediately.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse effects not listed in this leaflet, inform a physician. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax +48 22 49 21 309, e-mail: [email protected]. Reporting adverse reactions helps to gather further information on the safety of using the medicinal product.

5. How to store Allergopharma Provocation Test Solutions

Store in a refrigerator (2°C - 8°C).
Do not freeze.
Keep out of reach and sight of children.
Do not use Allergopharma Provocation Test Solutions after the expiry date stated on the packaging.

6. Contents of the Packaging and Other Information

What do Allergopharma Provocation Test Solutions Contain?
Allergopharma Provocation Test Solutions contain allergenic extracts of plant, animal, mould fungi and yeast origin, house dust mites, pollens, and food allergens.
The allergens are in powder form and must be completely dissolved before use.
The names of the allergens and their concentrations after dissolving the powder in 5 ml of solvent are indicated on the labels of the provocation test vials.
Allergen activity and concentration are expressed as: SBU – standardized biological units; BU – biological units; PNU – protein nitrogen units; or %w/v – weight/volume units.
List of allergens and concentrations – see Annex 1. Provocation test solutions are characterized by physicochemical and immunological analyses, including quantitative assessment of selected major allergens.

Other components of the medicinal product:
Powder
mannitol
Solvent
sodium chloride
sodium hydrogen carbonate
phenol
water for injections
Negative control solution:
sodium chloride
phenol
purified water

What Allergopharma Provocation Test Solutions Look Like and What the Packaging Contains
Due to the natural colouring of the raw materials used for extraction, test solutions may vary in colour.
The packaging contains:
Vials with powder and vials with 5 ml solvent, and/or a vial with 5 ml negative control solution with attached spray nozzle, and/or spray devices and nasal applicators included in the package, according to the order based on Annex 1.

Marketing Authorisation Holder and Manufacturer
Allergopharma GmbH & Co. KG
Hermann-Koerner-Str. 52
D-21465 Reinbek
Germany
Tel. +49 40 / 727 65-0
Fax +49 40 / 722 77 13
e-mail: [email protected]
For further information, please contact the representative of the marketing authorisation holder:
SUN-FARM Sp. z o.o.
ul. Dolna 21
05-092 Łomianki
Poland
Tel. 22 350 66 69
Fax 22 350 77 03

Annex 1 to the Patient Leaflet:
Allergenic Extracts for Provocation Tests

Plant-derived allergenic extracts (pollens)
101 Cypress - 5000 BU/ml
106 Common Nettle - 5000 SBU/ml
108 Silver Birch - 5000 SBU/ml
109 Nettle - 5000 BU/ml
110 Beech - 5000 BU/ml
114 Pedunculate Oak - 5000 BU/ml
115 Alder - 5000 BU/ml
116 Ash - 5000 BU/ml
121 Barley - 5000 BU/ml
126 Oat - 5000 BU/ml
129 Hazel - 5000 BU/ml
132 Elder - 5000 BU/ml
142 Lime - 5000 BU/ml
143 Dandelion - 5000 BU/ml
151 Olive - 5000 BU/ml
152 Poplar - 5000 BU/ml
153 Eastern Plane Tree - 5000 BU/ml
156 Ragweed - 5000 BU/ml
158 Rye - 5000 SBU/ml
161 Sorrel - 5000 BU/ml
168 Elm - 5000 BU/ml
169 Lanceolate Plantain - 5000 SBU/ml
170 Willow - 5000 BU/ml
173 Wheat - 5000 BU/ml
177 Timothy Grass - 5000 BU/ml

Animal-derived allergenic extracts (animal hair and dander, feathers)
304 Hamster hair - 5000 BU/ml
306 Dog hair - 5000 BU/ml
308 Rabbit hair - 5000 BU/ml
309 Cat hair - 5000 SBU/ml
311 Guinea pig hair - 5000 BU/ml
314 Horse hair - 5000 BU/ml
317 Cow hair - 5000 BU/ml
318 Wool - 5000 BU/ml
321 Parrot feathers - 5000 BU/ml

Allergenic extracts of mites
708 Dermatophagoides farinae - 5000 BU/ml
725 Dermatophagoides pteronyssinus - 5000 SBU/ml
728 Acarus siro - 5000 BU/ml
729 Lepidoglyphus destructor - 5000 BU/ml
730 Tyrophagus putrescentiae - 5000 BU/ml

Food allergenic extracts
588 Barley gluten - 1000 PNU/ml
589 Barley flour - 1000 PNU/ml
590 Oat flour - 1000 PNU/ml
592 Corn gluten - 400 PNU/ml
593 Corn flour - 800 PNU/ml
595 Rye gluten - 1600 PNU/ml
596 Rye flour - 1600 PNU/ml
599 Wheat flour - 1600 PNU/ml
600 Wheat gluten - 1600 PNU/ml

Allergenic extracts of mould fungi and yeasts
400 Alternaria tenuis - 5000 SBU/ml
401 Aspergillus fumigatus - 5000 BU/ml
402 Botrytis cinerea - 5000 BU/ml
405 Cladosporium herbarum - 5000 BU/ml
406 Curvularia lunata - 5000 BU/ml
407 Fusarium moniliforme - 5000 BU/ml
408 Helminthosporium halodes - 5000 BU/ml
410 Mucor mucedo - 5000 BU/ml
412 Penicillium notatum - 5000 BU/ml
413 Pullularia pullulans - 5000 BU/ml
414 Rhizopus nigricans - 5000 BU/ml
416 Serpula lacrymans - 5000 BU/ml

Mixtures of plant-derived allergenic extracts

006 Grasses 100% - 5000 SBU/ml
133 Cocksfoot
140 Meadow Fescue
157 English Ryegrass
177 Timothy Grass
178 Meadow Foxtail
179 Meadow Fescue
in equal parts

015 Grasses/Cereals 100% - 5000 BU/ml
006 Grasses 55%
121 Barley 10%
126 Oat 10%
158 Rye 15%
173 Wheat 10%

014 Weeds - 5000 BU/ml
106 Common Nettle
109 Nettle
143 Dandelion
169 Lanceolate Plantain
in equal parts

012 Trees I - 5000 BU/ml
115 Alder
129 Hazel
152 Poplar
168 Elm
170 Willow
in equal parts

013 Trees II - 5000 BU/ml
108 Silver Birch
110 Beech
114 Pedunculate Oak
153 Eastern Plane Tree
in equal parts
901 Negative control solution

Emergency Procedures During Provocation Tests

This scheme serves only as a general guideline; treatment should be adjusted according to the patient's clinical condition.