Lays birch

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LYS BIRCH

Composition:

Active substances: chemically modified allergen extract of birch and alder pollen:

birch 50%, alder 50% (Betula pendula 50%, Alnus incana 50%);

1 sublingual tablet contains 300 AU or 1000 AU;

Excipients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate.

AU – allergen unit, a dosing unit for specific immunotherapy products.

Pharmaceutical form. Sublingual tablets.

Main physicochemical properties: white, round tablets with a score line on one side and engraved numbers: 300 AU – with the number "3", 1000 AU – with the number "4".

Pharmacotherapeutic group.

Allergens. Allergen extracts. ATC code V01A A.

Pharmacological Properties

Lais Betula is a medicinal product for specific immunotherapy based on the use of chemically modified allergen extracts. The chemical modification involves carbamylation under alkaline conditions. This procedure ensures:

• modification of epitopes involved in IgE binding of allergenic components of the extract, as evidenced by a significant reduction in allergenicity determined by the EAST (Enzyme Allergosorbent Test)-inhibition method, thereby improving the safety profile;
• preservation of the immunogenic properties of the resulting product (i.e., the ability to induce a beneficial immune response). In addition, this procedure does not significantly alter the molecular size of the allergenic components of the resulting extract, which remains suitable for sublingual administration.

Pharmacodynamics

Specific sublingual immunotherapy (SLIT) is a treatment method involving repeated sublingual administration of specific allergens to modify the immune response to allergens in patients suffering from diseases where pathological allergic reactions are the dominant component. The complete and precise mechanism of action underlying the clinical effect of specific immunotherapy is not fully known or described. It is believed to be related to a significant influence on IgE-mediated inflammatory reactions associated with natural allergen exposure. It has been demonstrated that specific sublingual immunotherapy significantly reduces IgE-mediated inflammation, as shown by decreased allergen-induced inflammatory infiltrate (neutrophils and eosinophils) and adhesion molecules (ICAM-1) in the nasal cavity or conjunctiva. Functional blockade of various stages of IgE-mediated reactions prevents further triggering, amplification, and self-perpetuation of allergic inflammation.

The above information suggests that specific sublingual immunotherapy can significantly reduce allergic inflammation and plays an important role in protecting organs from damage.

It has been demonstrated that specific sublingual immunotherapy using Lais Betula leads to a significant reduction in allergen-specific cellular proliferation in the human body while simultaneously enhancing allergen-specific innate immunity. In particular, Lais Betula induces a shift from a Th2-type immune response (typical of allergic inflammation) towards a Th1-type immune response and activates regulatory T-cells, culminating in increased production of IL-10 cytokines. Collectively, these effects indicate that the mechanism of action of Lais Betula is associated with the induction of immunological tolerance to allergens responsible for allergic sensitization.

Pharmacokinetics

The pharmacokinetic properties of Lais Betula have not been studied due to the nature of the active substance (an extract, natural or allergoid, consisting of a mixture of various components). On the other hand, some of these components are recognized as major allergens. They can be purified and used in pharmacokinetic studies, which may provide useful information. For this purpose, volunteers in experimental settings received allergens or their chemical modifications (allergoids), radiolabeled, sublingually. These studies demonstrated that both natural and modified allergen extracts have a prolonged elimination half-life—over 20 hours—from the oral mucosa and buccal lymphoid tissues. Absorption into blood plasma begins 30 minutes after administration and reaches a plateau within 2 hours. Only in the case of the allergoid can intact molecules be detected in blood serum; whereas, with the natural allergen, only small molecular fragments are found in serum, confirming differences in pharmacokinetic profiles.

Such biological distribution data were obtained using the allergoid of the major allergen from house dust mites (Der p2) and the allergoid of the major allergen from wall pellitory (Parietaria) (Par j1). Since differences in the biological distribution profile of various allergens administered via the oral mucosa are not expected, a similar pattern is likely to occur with the use of allergoids of the major allergens from birch (Bet v1) and alder pollen.

Clinical characteristics.

Indications.

Treatment of birch and alder pollen-induced rhinitis, conjunctivitis, and allergic bronchial asthma in patients with clinically significant symptoms.

Diagnosis is established based on a positive skin prick test and/or positive specific IgE test to birch and alder pollen.

Contraindications.

• Hypersensitivity to any component of the medicinal product.
• Presence of a malignant neoplasm.
• Severe autoimmune disease, immune disorder, immunodeficiency, or immunosuppression.
• Chronic inflammatory disease.
• Acute inflammation in the oral cavity with severe symptoms.
• Pathology of target organs (e.g., cardiac or respiratory insufficiency, emphysema, bronchiectasis).
• Severe bronchial asthma.
• Bronchial obstruction, particularly with FEV1 < 70% of predicted value despite adequate pharmacological treatment.
• Partially controlled or uncontrolled bronchial asthma (according to the current GINA guidelines (Global Initiative for Asthma)).
• Conditions in which epinephrine (adrenaline) use is contraindicated.

Special precautions.

Unused medicinal product or waste material must be disposed of in accordance with national regulatory requirements.

Interaction with other medicinal products and other forms of interaction.

Interactions with other medicinal products have not been studied. Interactions with other medicinal products are unknown.

Concomitant therapy with symptomatic anti-allergic medications (e.g., corticosteroids, antihistamines, mast cell degranulation inhibitors) may improve patient tolerance to allergen-specific immunotherapy. This should be considered when temporarily discontinuing such medications. Although specific studies have not been conducted, interaction with food cannot be excluded.

Currently, there is no information regarding possible interactions between the medicinal product Lais birch and immunosuppressive agents; therefore, as a precaution, specific immunotherapy is not recommended.

There are no data on the potential risks of concomitant immunotherapy against other allergens during treatment with the medicinal product Lais birch.

Special precautions for use

Any local (e.g., oral or lip itching) and/or systemic adverse reactions (e.g., generalized pruritus, urticaria, skin rashes, nausea, cough, rhinorrhea or nasal congestion, general discomfort, or excitement/anxiety) occurring during specific immunotherapy should be reported immediately to the physician. The physician should adjust the therapeutic regimen and prescribe appropriate treatment depending on the severity of the allergic reaction (e.g., antihistamines, corticosteroids, mast cell stabilizers, β2-agonists).

In case of severe systemic reactions such as angioneurotic edema, difficulty in breathing or swallowing, development or exacerbation of asthma, voice changes, or arterial hypotension, immediate medical consultation is required. The physician must decide on the duration of therapy interruption (if necessary). In case of serious anaphylactic reactions, epinephrine (adrenaline) should be administered. The effect of epinephrine may be potentiated in patients receiving tricyclic antidepressants and/or monoamine oxidase inhibitors (MAOIs), potentially leading to a fatal outcome. This should be taken into account before initiating specific immunotherapy. In patients taking β-blockers, there may be no response to epinephrine used in the treatment of serious systemic reactions. Concomitant use of β-blockers requires consultation with a physician regarding the advisability of switching to an alternative medication.

Prior to initiating specific immunotherapy, allergy symptoms should be adequately stabilized with appropriate pharmacological treatment.

For patients suffering from bronchial asthma, the medicinal product Lais birch should be used as an adjunct to pharmacological therapy, not as a replacement for prior treatment. It is recommended not to abruptly discontinue asthma control medications after starting Lais birch. Dose reduction of asthma control medications should be performed gradually under physician supervision and in accordance with bronchial asthma treatment protocols.

If an influenza-like illness with fever or respiratory tract infection occurs, treatment should be temporarily suspended until the infection resolves. It is recommended to consult a physician regarding dose adjustment.

There is no clinical experience with concomitant administration of antiviral or antibacterial vaccines during therapy with Lais birch. If vaccination is required, immunization should be performed one week after discontinuation of Lais birch, and immunotherapy may be resumed two weeks after vaccination.

Alcohol consumption and physical exertion should be avoided for several hours after taking the medicinal product.

Oral inflammation

If the patient has severe oral inflammation (e.g., oral lichen planus, oral ulcers, or candidal stomatitis), oral wounds, or has undergone oral surgery, including tooth extraction/loss, initiation of therapy with Lais birch should be postponed. If therapy has already been started, it should be temporarily interrupted until healing of the oral lesion is complete.

The product contains lactose; therefore, it is not recommended for patients with rare hereditary conditions of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of specific immunotherapy agents in pregnant women are limited, as studies on reproductive toxicity and fetal development have not been conducted.

Due to the limited safety data, initiating specific immunotherapy during pregnancy is contraindicated because of the potential risk to the pregnant woman and/or fetus associated with possible systemic reactions and the need for concomitant medications to manage them. If pregnancy occurs during the induction phase, discontinuation of further immunotherapy should be considered.

Breastfeeding

There are no data on the use of Lais birch during breastfeeding. No effect on the breastfed infant is expected.

Fertility

There are no clinical data on the effect of Lais birch on fertility.

Ability to affect reaction speed when driving or operating machinery

As with other medicinal products used for specific immunotherapy, fatigue may occur. Lais birch may have a slight influence on the ability to drive vehicles or operate machinery due to reduced patient attention.

Method of Administration and Dosage

For use in adults, adolescents, and children aged 5 years and older.

Diagnosis is established based on a positive skin test reaction and/or results of testing for specific IgE antibodies to birch and alder pollen.

The dosing regimen for specific immunotherapy should always be selected individually. The physician selects the dose and frequency of administration according to the course of the disease. The dosing regimen described below is merely an example.

Dosing

Treatment must be administered by a physician experienced in the management of allergic diseases.

The patient may self-administer the medication unless otherwise instructed by the physician. To ensure proper patient training in the administration of the medicinal product and to facilitate information exchange between physician and patient regarding possible adverse reactions and necessary measures in response to such reactions, or in case of safety concerns, the physician may require that the first dose be taken under medical supervision.

Treatment may be initiated at least 3 months before the expected start of the birch and alder pollen season and continued throughout the pollen season for 2 months.

Allergen-specific immunotherapy guidelines recommend annual treatment for 3–5 years.

INITIATION OF THERAPY

Treatment is initiated with 300 AQ tablets according to the dosing schedule outlined below.

Dosing Schedule

SUPPORTIVE THERAPY

After the initial phase, seasonal treatment is continued by taking 1 tablet of 1000 SQ once daily, 1–5 times per week (e.g., from Monday to Friday).

The dosing regimen may be adjusted by the physician depending on the patient's clinical and therapeutic response.

The tablet should be placed in the mouth and held under the tongue for several minutes until completely dissolved, after which it may be swallowed.

Tablets should not be taken during meals.

If treatment is interrupted for more than 2 weeks, the patient should consult a physician for recommendations on appropriate dose adjustment. Therapy should be resumed starting from the last tolerated dose.

Children.

Use of the medicinal product Lais Birch in children under 5 years of age is not recommended, as safety and efficacy data in this age group are lacking.

Overdose.

Adults with allergy to birch and alder pollen participated in clinical trials and received the medicinal product at doses up to 2000 SQ.

No adverse effects related to overdose were observed. However, administration of doses exceeding the recommended dose may cause local or systemic allergic reactions. If severe systemic reactions occur, such as angioedema, difficulty in swallowing, breathing difficulties, acute bronchial asthma attack, voice changes, arterial hypotension, or sensation of a lump in the throat, the medicinal product must be discontinued immediately and medical advice should be sought.

Treatment is symptomatic.

Adverse Reactions

The information on adverse reactions presented in the table below is based on data from controlled clinical trials involving adult patients with birch and alder pollen-induced rhinoconjunctivitis. Information on the frequency of adverse drug reactions is based on data from 247 patients who received active treatment.

Adverse reactions were classified by frequency according to the recommended MedDRA (Medical Dictionary for Regulatory Activities) system: 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), frequency not known (cannot be estimated from the available data).

Table

The frequency of adverse reactions during the post-marketing period cannot be determined, as the information was obtained from spontaneous reports. Therefore, the frequency of these adverse events is classified as unknown.

Infections and infestations: nasopharyngitis, conjunctivitis.

Respiratory system disorders: asthma, dysphonia, cough.

Gastrointestinal disorders: gastrointestinal disturbances, abdominal pain, nausea, oral swelling.

Skin and subcutaneous tissue disorders: urticaria, pruritus, skin rash, drug eruption, alopecia areata.

Musculoskeletal and connective tissue disorders: bone pain.

General disorders: increased fatigue.

Description of selected adverse reactions

If a significant adverse reaction occurs during therapy, the patient should immediately inform their physician. Depending on the severity of the clinical presentation, consideration should be given to interrupting therapy, adjusting the dose, and, if necessary, administering an antiallergic agent.

In case of sudden worsening of asthma symptoms or severe systemic reactions, angioneurotic edema, difficulty swallowing, breathing difficulties, voice changes, arterial hypotension, or a sensation of a lump in the throat, immediate medical attention should be sought.

Children and adolescents

The use of Lys Betula medicinal product in children under 5 years of age is not recommended due to lack of data in this patient group.

Reporting of suspected adverse reactions

After marketing authorization of a medicinal product, it is very important to report suspected adverse reactions. This allows continuous monitoring of the benefit-risk profile of the medicinal product. Healthcare professionals should report any adverse reactions via the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

Sublingual tablets № 40: 10 tablets of 300 AU (1 blister pack) and 30 tablets of 1000 AU (3 blister packs) in a cardboard box;

sublingual tablets № 70: 10 tablets of 300 AU (1 blister pack) and 60 tablets of 1000 AU (6 blister packs) in a cardboard box.

Prescription status.

Prescription only

Manufacturer.

LOFARMA S.p.A.

Manufacturer's location and address of place of business.

VIALE CASALA, 40 - 20143 MILAN (MI), Italy.