Non-infectious allergens household group

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Non-infectious Household Allergens

Composition:

Active substances: household allergens (Allergena domestica):

1 ml of solution contains 10,000 PNU of dust allergen,

1 ml of solution contains 10,000 PNU of dust allergen enriched with Dermatophagoides pteronyssinus,

1 ml of solution contains 10,000 PNU of dust allergen enriched with Dermatophagoides farinae,

1 ml of solution contains 10,000 PNU of dust allergen enriched with Acarus siro,

1 ml of solution contains 10,000 PNU of library dust allergen,

1 ml of solution contains 10,000 PNU of pillow feather allergen,

1 ml of solution contains 10,000 PNU of daphnia allergen;

mixed household allergens (mixtures of the listed allergens taken in equal proportions) of the following composition:

1 ml of solution contains 10,000 PNU of mixed household allergen No. 5 (from dust enriched with Dermatophagoides pteronyssinus; dust enriched with Dermatophagoides farinae; dust enriched with Acarus siro; pillow feathers);

Excipients: sodium chloride, disodium phosphate dodecahydrate (sodium phosphate dibasic), potassium dihydrogen phosphate (potassium phosphate monobasic), phenol, water for injections.

1 vial contains 5 ml of allergen (10,000 PNU/ml).

Note: 1 PNU (Protein Nitrogen Unit) – an international unit accepted for determining the concentration of protein nitrogen in allergens, equal to 0.00001 mg of protein nitrogen.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: transparent liquids ranging in color from colorless to dark brown.

Pharmacotherapeutic group. Allergen extracts. Bird feather allergens. ATC code V01A A01.

Allergen extracts. House dust allergens. ATC code V01A A03.

Immunological and biological properties.

Pharmacodynamics.

Mechanism of action. The active component of household allergens is a protein-polysaccharide complex which, when used in skin and provocation tests, enables diagnosis of patient sensitization to the respective allergen. If necessary, the preparation may be used for allergen-specific immunotherapy (AIT) in patients hypersensitive to the corresponding household allergens. The ability of allergen components to interact with specific IgE-class antibodies (reagins) in the patient and to elicit a reaction in a sensitized organism determines the diagnostic potential of the preparation, while multifactorial effects on the patient's immune system provide the therapeutic effect of allergen-specific immunotherapy (induction of tolerance to the respective allergens).

Allergen-specific immunotherapy exerts a therapeutic effect affecting all stages of the allergic process, including its immunological phase, and leads to a shift in immune response from Th2-type to Th1-type, suppresses both early and late phases of IgE-mediated allergic reaction, inhibits the cellular component of allergic inflammation and non-specific tissue hyperreactivity.

During allergen-specific immunotherapy the following occurs: increased production of blocking antibodies, reduced release of allergy mediators, enhanced activity of suppressor cells and mechanisms; increased production of IL-2-producing cells, enhanced function of Th1 helper lymphocytes and reduced Th2 activity, phenotypic shift of CD4+ cells from Th2 to Th1, increased functional activity of T-lymphocytes, enhanced function of isotype-specific T-suppressors, regulation of IgE induction by idiotypic antibodies, decreased reactivity of mediator-producing cells.

Pharmacokinetics.

Not studied. The effect of the preparation is due to the combined action of its protein components, making pharmacokinetic studies impossible, as all components cannot be traced using markers or biological assays. For the same reasons, metabolites of the preparation cannot be identified.

Clinical characteristics.

Indications.

Specific diagnosis of allergic diseases by detecting sensitization to household allergens and allergen-specific immunotherapy of hypersensitivity to household allergens.

Specific diagnosis of allergic diseases

For diagnostic purposes, the preparations are used to perform skin tests by the prick test method (scarification test and provocation tests may also be performed).

Allergen-specific immunotherapy of allergic diseases

Allergen-specific immunotherapy for hypersensitivity to household allergens is administered to patients in whom sensitization to these allergens has been confirmed by skin testing.

Allergen-specific immunotherapy is indicated when:

• IgE-mediated nature of the disease has been confirmed;
• the disease has a prolonged course with pronounced clinical manifestations;
• there is clear evidence of the role of household allergens;
• complete elimination of the allergen is not possible;
• the required standardized allergens are available.

Contraindications.

To identify contraindications, the physician examines the patient on the day of skin testing or administration of allergen-specific immunotherapy (AIT).

Contraindications for skin testing with allergens

Age under 1 year for prick testing and under 3 years for scarification testing; exacerbation of the allergic disease being diagnosed; skin pathology at the test site (e.g., eczema); acute respiratory infections with elevated body temperature; chronic diseases in decompensation stage; active tuberculosis in any location; acute psychiatric disorders; systemic diseases (collagenoses) and oncological diseases.

Pregnancy is a contraindication for skin testing (see section "Use during pregnancy or breastfeeding").

The use of beta-adrenergic receptor antagonists (beta-blockers) is a risk factor for developing anaphylactic reactions.

Contraindications for allergen-specific immunotherapy (AIT)

Severe immunopathological conditions and immunodeficiencies (including HIV); oncological diseases; severe psychiatric disorders; acute infections and chronic infections in the phase of exacerbation; elevated body temperature (above 38.5 ºC); infectious diseases (viral hepatitis, tuberculosis); uncontrolled bronchial asthma (FEV1 less than 70% despite adequate pharmacotherapy, including severe forms of bronchial asthma); asthma exacerbation within 3 days prior to dose administration; cardiovascular diseases with potential complications when using adrenaline (epinephrine); use of beta-adrenergic receptor antagonists (beta-blockers), including topical formulations, and ACE inhibitors (for treatment of hypertension or ischemic heart disease); severe cardiovascular diseases; history of anaphylactic shock during AIT; age under 5 years (for subcutaneous AIT); diabetes mellitus; uncontrolled thyrotoxicosis; myocardial infarction within the past year; active autoimmune diseases; pregnancy and breastfeeding (see section "Use during pregnancy or breastfeeding"); physical exertion immediately after dose administration; hypersensitivity to excipients of the preparation.

Special precautions.

No special warnings or precautionary measures are required when using allergen preparations.

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

Interaction with other medicinal products and other forms of interaction.

Specific diagnosis of allergic diseases

The use of antihistamines and glucocorticosteroids affects the reliability of allergen skin testing (reduces papule size up to complete absence).

The use of H2-histamine receptor blockers, cromoglycate, corticosteroids in doses up to 15 mg of prednisolone, and theophylline derivatives does not affect the results of allergy testing. A possible effect may occur with topical application of steroid ointments. Beta-blockers may enhance skin reactions.

Allergen-specific immunotherapy of allergic diseases

AIT should not be performed during treatment with antibiotics, cytostatics, or immunobiological agents. It may be combined with medications used for the treatment of allergic diseases (non-sedating antihistamines, cromones, bronchodilators, topical glucocorticosteroids, anti-leukotriene agents).

Do not use simultaneously with beta-blockers.

Food intake does not affect allergen diagnosis or therapy.

Special precautions for use.

Skin testing and allergen-specific immunotherapy (AIT) must be prescribed exclusively by an allergist or pediatric allergist experienced in managing allergic diseases, who has undergone specialized training, including emergency management of anaphylaxis, and must be performed under their supervision in an allergology office or inpatient setting.

Skin tests with allergens and AIT are performed only after the physician has obtained written informed consent from the patient!

Specific diagnosis of allergic diseases

Indications for skin testing with allergens include clinical history and results of clinical and laboratory examinations.

Skin tests are applied on the inner surface of the forearm, at a distance of (30±10) mm from each other, or on the skin of the back. Up to 30 tests may be performed simultaneously if the prick test method is used, or up to 15 tests if the scarification method is used. Performing skin tests with allergens in children under 1 year of age using the prick test method, or under 3 years of age using the scarification method, is not recommended. For children, the number of allergen skin tests (using the prick test method) should not exceed their age in years (for scarification – half that number).

Skin tests are performed using allergens containing 10,000 PNU per 1 mL. For patients with a high degree of sensitization, a preparation with a concentration of 5,000 PNU per 1 mL should be used.

Temporary contraindications for skin testing include the use of antihistamines (up to 10 days), systemic glucocorticosteroids (up to 14 days), or topical glucocorticosteroid creams applied to the skin area where testing will be performed (up to 30 days). Due to the large number of drugs used in treating allergic diseases and the emergence of new medications, these time intervals are approximate and may vary depending on the specific drug used by the patient. Therefore, skin tests with allergens should only be performed after a positive skin reaction to histamine has been restored!

Allergen-specific immunotherapy for allergic diseases

AIT with household allergens is performed in patients in whom sensitization to these allergens has been confirmed by skin testing. During AIT, allergens are administered subcutaneously into the outer third of the upper arm (in the groove between the deltoid and triceps muscles). Other routes of allergen administration for therapeutic purposes may only be used based on regulatory documents (relevant instructions, protocols, standards, or methodological recommendations) approved by the Ministry of Health of Ukraine. The allergist is responsible for preparing allergen dilutions under aseptic conditions for AIT and for the use of prepared dilutions.

AIT regimens may vary—from accelerated to slow. This instruction provides a standard AIT regimen for adults and children. The decision to use alternative regimens is made by the allergist based on the patient’s condition, age, necessity of AIT, and the etiology of the allergic disease. Typically, AIT is initiated after allergometric titration (by performing a prick test or intradermal injection of sequential allergen dilutions to determine the lowest concentration that elicits a skin reaction). AIT is started at a dose 10 times lower than the one causing a skin reaction. If a skin reaction to a group of allergens is detected, the allergist must determine exactly which allergen(s) should be used for AIT. Performing AIT with a mixture of more than four components is considered undesirable.

During skin testing and AIT, systemic allergic reactions and anaphylactic shock may occur in particularly sensitive patients. After allergen injection, the patient must remain under the physician’s supervision for at least 30 minutes! Every office where AIT is administered must have an emergency kit available for immediate management of anaphylaxis.

In case of anaphylactic reactions, allergen administration must be stopped immediately, and management must follow the protocol for emergency medical care in anaphylactic shock in children and adults, approved by the order of the Ministry of Health of Ukraine.

Relative or temporary contraindications for AIT

Age over 55 years; skin diseases; chronic infectious diseases; weakly positive skin tests with allergens; lack of efficacy of previous AIT (if performed); exacerbation of the primary allergic disease; exacerbation of any concomitant disease; any intercurrent illness in an acute phase; use of MAO inhibitors in combination with sympathomimetics; vaccination (see section "Vaccination").

Limitations for AIT use

Insufficient patient understanding of the necessity of AIT and poor compliance; long duration of allergic disease (10 years or more); delayed positive skin tests with allergens; presence of non-specific hyperreactivity; epidermal allergy; sensitization to food, drug, or chemical allergens; high sensitivity to 5 or more allergens.

Vaccination

Vaccination is not performed during the first phase of dose escalation in AIT.

It is recommended to perform routine vaccination one month before starting AIT or, if possible, to postpone vaccination until after completion of the main AIT course. In long-term AIT (continuous treatment for 3 or more years), vaccination may be performed during the second, maintenance phase, provided the following conditions are met:

• AIT injection and preventive vaccination should not be administered on the same day;
  • vaccination should be performed no earlier than 2–3 weeks after allergen injection;
  • if no adverse reactions occur after vaccination, the next allergen injection may be administered no earlier than:
• 2 weeks after inactivated vaccines;
• 4 weeks after live vaccines;
• 8–12 weeks after BCG vaccine;
• 1 week after tuberculin skin test.

AIT should be continued using the same allergen dilution that was used before vaccination.

Skin tests with allergens may be performed 10–15 days before vaccination and 1.5–2 months after administration of vaccine preparations.

The medicinal product contains potassium and sodium compounds; however, their content is less than 1 mmol (39 mg)/dose for potassium and 1 mmol (23 mg)/dose for sodium, allowing the conclusion that this medicinal product is practically free of potassium and sodium.

Use during pregnancy or breastfeeding.

Pregnancy is a contraindication for skin testing and AIT (see section "Contraindications") due to the risk of systemic allergic reactions that may cause uterine contractions and the potential need for epinephrine (adrenaline), which may cause constriction of the umbilical artery.

Treatment should not be initiated during pregnancy. If pregnancy occurs during ongoing AIT, further use of allergens should be determined jointly by the allergist and obstetrician-gynecologist, considering the potential risk to mother and child in case of systemic allergic reaction or anaphylactic shock. AIT should be discontinued if pregnancy occurs during the dose escalation phase. AIT may be continued if pregnancy begins during the maintenance phase.

AIT should not be initiated during breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Allergen preparations do not affect the ability to drive or operate machinery.

Method of Administration and Dosage

Technique for Performing Skin Allergy Tests with Allergens

Skin tests are performed on the inner surface of the forearm or on the skin of the back.

Allergens, diluent for allergens (negative control), and 0.01% histamine dihydrochloride solution for skin diagnosis of allergic diseases (positive control) are applied under aseptic conditions. One drop each of allergen, diluent for allergens, and 0.01% histamine dihydrochloride solution for skin diagnosis of allergic diseases is placed on the skin disinfected with 70% ethyl alcohol, using sterile dropper caps (see the instructions for medical use).

Prick Test. Using sterile disposable lancets for prick testing, individual for each patient and each preparation, puncture the skin through the drops of allergen, diluent for allergens, and 0.01% histamine dihydrochloride solution for skin diagnosis of allergic diseases until resistance is met at the lancet's stop.

Scratch (Scarification) Test. Using sterile scarifiers, individual for each patient and each preparation, make scratches through the drops of allergen, diluent for allergens, and 0.01% histamine dihydrochloride solution for skin diagnosis of allergic diseases, with scratches up to 5 mm in length.

Evaluation of Skin Test Results

Skin test results are evaluated after 15–20 minutes (immediate-type reaction). The skin reaction to histamine should be positive (typically a wheal of 3–5 mm in diameter forms); if the skin does not react to histamine, allergen (or mixed allergen) testing is not performed. The skin reaction to the diluent should be negative; if a positive reaction occurs to the diluent, the allergen (or mixed allergen) test result is disregarded.

Skin Test Evaluation Scheme

Allergen-specific immunotherapy (AIT) procedure

The potential risk of developing severe allergic reactions and/or delayed systemic reactions during AIT, as well as the management plan in such cases, must be thoroughly discussed with patients.

During AIT, allergens are administered subcutaneously to the patient in the outer third of the arm (in the groove area between the deltoid and triceps muscles).

The interval between allergen doses during AIT is determined by the allergist physician. It may range from 1 day to 1 week or longer.

After allergen injection, the patient must remain under the supervision of the allergist physician for at least 30 minutes!

Standard protocol for allergen-specific immunotherapy

The standard protocol for conducting allergen-specific immunotherapy (AIT) in children corresponds to the protocol used in adults.

The duration of AIT is determined by the allergist. Usually, the maximum effect of AIT develops within 1–2 years after initiation. The optimal duration of AIT is considered to be 3–5 years. If AIT shows no effect within one year, it should be discontinued.

Children.

Skin testing with allergens using the prick test method is not recommended in children under 1 year of age, and using the scarification method is not recommended in children under 3 years of age.

The number of allergen skin tests (prick test method) in children should not exceed the numerical value of their age (for scarification, this number should be half).

Allergen-specific immunotherapy (subcutaneous) is not recommended in children under 5 years of age. Allergen-specific treatment in children is generally conducted according to the standard protocol; accelerated treatment protocols (AIT) are not recommended.

When conducting allergen-specific immunotherapy in children, current regulations issued by the Ministry of Health of Ukraine must be followed.

Overdose.

Specific diagnosis of allergic diseases

Cases of overdose with allergen preparations during skin testing have not been reported.

Allergen-specific immunotherapy of allergic diseases

Exceeding the dose of allergens administered during allergen-specific immunotherapy may lead to the development of systemic and local adverse reactions in the patient.

Adverse reactions.

Adverse reactions are usually associated with violations of skin testing and allergen-specific immunotherapy (ASIT) procedures: incorrect performance of prick tests, skin testing on infected skin, allergen overdose, incorrect preparation of allergen solutions for ASIT, administration of treatment by untrained personnel, improper allergen injection technique, direct intravascular injection of allergens, performing ASIT during undiagnosed intercurrent infection, lack of monitoring of vital signs before allergen administration (arterial pressure, pulse, baseline spirometry parameters, etc.).

Potential adverse reactions may develop 10 minutes or more after allergen injection and may manifest as:

• disorders of the respiratory system, thoracic organs, and mediastinum: cough, dyspnea, bronchospasm, sneezing, nasal congestion, and itching;
• disorders of the skin and subcutaneous tissue: rash, facial flushing, urticaria, edema, pruritus;
• gastrointestinal disorders: abdominal pain;
• nervous system disorders: headache, drowsiness;
• psychiatric disorders: excitement;
• eye disorders: eye redness, lacrimation;
• musculoskeletal and connective tissue disorders: arthralgia;
• immune system disorders: anaphylactic reactions;
• general disorders and injection site reactions: general weakness, increased body temperature, sensation of warmth throughout the body, pain and itching at the injection site, formation of a papule, swelling, and hyperemia at the injection site. Local reactions usually resolve spontaneously or require application of cold to the injection site.

Reporting of suspected adverse reactions.

Reporting of adverse reactions after drug registration is of great importance.
This enables continuous monitoring of the benefit-risk balance associated with drug use. Healthcare professionals should report any adverse reactions through the national reporting system.

Shelf life.

2 years.

The shelf life of allergens closed with dropper caps, used for skin testing and stored in a refrigerator, is 1 year, but not exceeding the total shelf life indicated on the vial. The shelf life of allergens after dilution is 1 month; when diluted within the range of 0.01 to 1000 PNU/mL – 1 week.

Storage conditions.

Store in a light-protected place at a temperature of 2 to 8 °C. Do not freeze.
Keep out of reach of children.

Packaging.

5 mL of allergen in glass vials.

As a set in a cardboard box containing 1 vial of allergen – 5 mL (10000 PNU/mL), 1 sterile dropper cap.

Each box contains an instruction for medical use.

Prescription category. By prescription only.

Manufacturer.

LLC "Immunolog", Ukraine.

Manufacturer's address and place of business.

5 Dmytro Mayboroda Street, Vinnytsia, Vinnytsia Oblast, 21036, Ukraine.