Lais kit

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Lais Kit

Composition:

Active substance: chemically modified allergen extract of cat dander (Felis domesticus 100%);

1 sublingual tablet contains 300 or 1000 allergen units (AU);

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

AU – allergen unit, the dosing unit of specific immunotherapy products.

Pharmaceutical form.

Sublingual tablets.

Main physicochemical properties: white, round, smooth, homogeneous tablets, flat on one side with a score line and embossed number «3» for 300 AU or «4» for 1000 AU; the other side of the tablet is convex.

Pharmacotherapeutic group.

Allergens. Allergen extracts. ATC code: V01AA11.

Pharmacological Properties

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

• Modification of epitopes responsible for IgE binding of the allergen component of the extract, as evidenced by a significant reduction in allergenic activity (allergenicity), determined by the enzyme allergosorbent inhibition test, 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 allergen component 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 these allergens in patients suffering from diseases in which the allergic component plays a key pathogenic role. The complete and precise mechanism of action underlying the clinical effect of specific immunotherapy is not fully understood or documented. It is believed to be associated with significant interference in IgE-mediated inflammatory reactions related to natural allergen exposure. It has been demonstrated that specific sublingual immunotherapy induces a significant reduction in IgE-mediated inflammation, manifested by decreased allergen-induced inflammatory infiltration (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 initiation, amplification, and self-perpetuation of allergic inflammatory mechanisms.

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

In particular, it has been confirmed that specific sublingual immunotherapy with monomeric allergoids derived from various allergen extracts (e.g., house dust mite allergens, grass and tree pollens, etc.) induces a significant reduction in allergen-specific cell proliferation in humans while simultaneously enhancing allergen-specific innate immunity. More precisely, monomeric allergoids promote a shift from a Th2-type immune response (typical of allergic inflammation) to a Th1-type immune response and activate regulatory T cells, culminating in increased release of the anti-inflammatory cytokine IL-10. Collectively, these effects indicate that the mechanism of action of Lais Kit is associated with the induction of immunological tolerance to allergens responsible for allergic sensitization.

Pharmacokinetics

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

Similar data on biological distribution have been obtained using allergoids of the major allergen of house dust mites (Der p2) and the major allergen of Parietaria pollen (Par j1). Since no differences in biological distribution profiles are expected among various allergens administered via the oral mucosa, a similar pattern is likely to occur with allergoids of the major cat allergen (Fel d 1).

Clinical characteristics.

Indications.

Lais Kit is used for the treatment of allergic rhinitis, conjunctivitis, and allergic bronchial asthma caused by cat hair in patients with clinically significant symptoms.

Diagnosis is established based on a positive skin prick test and/or results of specific IgE testing to cat hair.

Contraindications.

• Hypersensitivity to any component of the medicinal product.
• Presence of malignant neoplasms.
• Severe autoimmune diseases, immune system disorders, immunodeficiencies, or immunosuppression.
• Chronic inflammatory diseases.
• Acute inflammation in the oral cavity with severe symptoms.
• Involvement of "shock organs" (e.g., cardiovascular insufficiency, emphysema, bronchiectasis).
• Severe bronchial asthma.
• Bronchial obstruction, particularly with FEV1 < 70% of predicted value after appropriate pharmacological treatment.
• Partially controlled or uncontrolled bronchial asthma (according to the current GINA guidelines (Global Initiative for Asthma)).
• Conditions where epinephrine use is contraindicated.

Allergen-specific immunotherapy should not be initiated during pregnancy.

Safety precautions.

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

Interaction with other medicinal products and other types of interactions.

Studies on interactions with other medicinal products have not been conducted. 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 performed, interactions with food cannot be excluded.

Currently, there is no information available on possible interactions between Lais Kit and immunosuppressive agents; therefore, as a precautionary measure, specific immunotherapy is not recommended in such cases.

There are no data on potential risks of concomitant immunotherapy with other allergens during treatment with Lais Kit.

Special precautions for use.

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

In the event of severe systemic reactions such as angioedema, difficulty breathing or swallowing, development or exacerbation of bronchial asthma, voice changes, or arterial hypotension, immediate consultation with the physician is required. The physician must decide whether to suspend the therapy temporarily (and for how long) or discontinue it altogether. In cases of serious anaphylactic reactions, epinephrine (adrenaline) may be administered. The effect of epinephrine may be potentiated in patients receiving tricyclic antidepressants and/or monoamine oxidase inhibitors (MAOIs) and/or catechol-O-methyltransferase inhibitors (COMT inhibitors); a fatal outcome is possible. 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. When β-blockers are used concomitantly, consultation with the physician regarding the possibility of replacing the β-blocker with an alternative therapy is recommended.

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

For patients suffering from bronchial asthma, the medicinal product Lyss Kit should be used as an adjunct to asthma medication and not as a substitute for prior treatment. It is recommended not to abruptly discontinue asthma control medications after starting Lyss Kit. Dose reduction of asthma control medications should be performed gradually under physician supervision and in accordance with guidelines for bronchial asthma management.

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

There is no clinical experience with antiviral or antibacterial vaccination during therapy with Lyss Kit. As a precautionary measure, if vaccination against any pathogens is required, immunization should be performed one week after discontinuation of Lyss Kit; 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), oral wounds, or oral tissue damage following oral surgery, including tooth extraction/loss, initiation of therapy with Lyss Kit 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 problems such as galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy

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

Due to the limited safety data available, initiating specific immunotherapy during pregnancy is contraindicated because of the potential risk to the pregnant woman and/or the fetus, related to the possibility of systemic reactions and the need for medication to manage them. If pregnancy occurs during the induction phase of this therapy, discontinuation of immunotherapy should be considered.

Breastfeeding

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

Fertility

Clinical data on the effect of Lyss Kit on fertility are lacking.

Ability to affect reaction speed when driving or operating machinery.

As with other medicinal products used for specific immunotherapy, fatigue may occur. Lyss Kit may have a slight influence on the ability to drive or operate machinery due to reduced concentration levels in patients.

Method of administration and dosage.

This medicinal product is intended for use in adults, adolescents, and children aged 5 years and older.

Diagnosis is confirmed by a positive skin test reaction and/or by specific IgE testing for cat allergens (epithelium).

The dosing regimen for specific immunotherapy should always be selected individually. The physician selects the dose and frequency of administration based on the course of the disease. The dosing regimen described below is provided as an example only.

Dosing

Therapy must be initiated and supervised by a physician experienced in the treatment of allergic diseases.

Patients 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 communication between physician and patient regarding possible adverse reactions and necessary measures in case of such events, or in case of any safety concerns, the physician may require that the first dose be administered under medical supervision.

Treatment may be initiated at any time of the year and should be continued throughout the entire year.

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

INITIATION OF THERAPY

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

Dosing schedule

MAINTENANCE THERAPY

After the initial treatment phase, continue taking 1 tablet of 1000 AU once or twice weekly throughout the entire year.

The dosing regimen may be adjusted by the physician according to the patient's clinical and therapeutic needs.

The tablet should be placed in the mouth and held under the tongue for several minutes until complete disintegration, 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 regarding appropriate dosage adjustment. Therapy should be restarted at the last tolerated dose.

Children.

The use of the medicinal product Lys-Kid in children under 5 years of age is not recommended due to lack of safety and efficacy data in this patient age group.

Overdose.

Adult patients with cat hair allergy participated in clinical trials and received the medicinal product at doses up to 2000 AU daily.

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, dyspnea, voice changes, or throat tightness, the medicinal product must be discontinued immediately and medical advice should be sought.

Treatment is symptomatic.

Adverse Reactions

The frequency of adverse reactions during the post-marketing period cannot be determined, as information on them comes from spontaneous reports or observational studies. Therefore, the frequency of these adverse events is classified as unknown.

Auditory system disorders: inner ear inflammation, tinnitus.

Gastrointestinal disorders: oral hypoaesthesia, diarrhoea, oral oedema, dyspepsia, abdominal pain, tooth discoloration.

Metabolism and nutrition disorders: decreased appetite.

Respiratory, thoracic and mediastinal disorders: pharyngeal oedema, dyspnoea, throat tightness, tracheitis, rhinorrhoea, upper airway cough syndrome.

Skin and subcutaneous tissue disorders: rash, erythema, pruritus, urticaria, facial swelling.

General disorders: malaise, tracheal obstruction.

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 the occurrence of severe systemic reactions, angioneurotic oedema, difficulty in swallowing, breathing difficulties, voice changes, arterial hypotension, or throat tightness, immediate medical attention is required.

Reporting of adverse reactions

Reporting adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

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

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

Prescription status.

Prescription only.

Manufacturer.

LOFARMA S.P.A.

Manufacturer's location and address of its business premises.

VIALE CASALBA, 40 - 20143 MILAN (MI), Italy