Lays herbs

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Lais Grass

Composition:

Active substances: chemically modified allergen extract of grass pollen:

Holcus lanatus 33 %, Phleum pratense 33 %, Poa pratensis 33 %;

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

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

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

Pharmaceutical form. Sublingual tablets.

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

Pharmacotherapeutic group.

Allergens. Allergen extracts. ATC code V01AA.

Pharmacological Properties

Lais Herbs is a medicinal product for specific immunotherapy based on the use of chemically modified allergen extracts. The chemical modification involves a carbamylation reaction 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 allergenic activity (allergenicity) determined by the EAST (enzyme allergo-sorbent 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 assumed that the effect is related to a significant influence on IgE-mediated inflammatory reactions associated with natural allergen exposure. It has been demonstrated that specific sublingual immunotherapy leads to a significant reduction in IgE-mediated inflammation, as evidenced 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 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 the medicinal product Lais Herbs leads to a significant reduction in allergen-specific cellular proliferation in the human body while simultaneously enhancing allergen-specific innate immunity. In particular, Lais Herbs induces a shift from a Th2-type immune response (typical of allergic inflammation) to a Th1-type immune response and activates regulatory T cells, resulting in increased production of the cytokine IL-10. Collectively, these effects indicate that the mechanism of action of Lais Herbs is associated with the induction of immunological tolerance to allergens responsible for allergic sensitization.

Pharmacokinetics

The pharmacokinetic properties of the medicinal product Lais Herbs have not been studied due to the nature of the active substance (an extract, natural or chemically modified allergoid, consisting of a mixture of various components). However, 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 chemically modified forms (allergoids), labeled with radionuclides, sublingually. These studies demonstrated that both natural and modified allergen extracts are characterized by 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 allergoids can intact molecules be detected in blood serum; in contrast, with natural allergens, 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 of house dust mites (Der p2) and the allergoid of the major allergen of Parietaria pollen (Par j1). Since significant 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 grass pollen allergens (Phl p1 or Phl p5).

Clinical characteristics.

Indications.

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

Diagnosis is established based on a positive skin test reaction and/or specific IgE test results to grass pollen.

Contraindications.

• Hypersensitivity to any component of the medicinal product.
• Presence of malignancy.
• Autoimmune disease, immune deficiency, or immunosuppression.
• Chronic inflammatory disease.
• Acute inflammation in the oral cavity with severe symptoms.
• Target organ pathology (e.g., cardiac or respiratory 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.

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.

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, interaction with food cannot be excluded.

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

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

Special precautions for use

Any local (e.g., oral or lip pruritus) and/or systemic (e.g., generalized pruritus, urticaria, skin rashes, nausea, cough, rhinorrhea or nasal congestion, general malaise, and excitation/anxiety) adverse reactions occurring during specific immunotherapy should be reported to the physician immediately. The physician must 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 the event of severe systemic reactions such as angioneurotic edema, difficulty 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 cases of serious anaphylactic reactions, adrenaline (epinephrine) should be administered. The effect of adrenaline 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 substituting the medication.

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

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

If influenza-like illness with fever or respiratory tract infections occur, 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 administering antiviral or antibacterial vaccination during therapy with the medicinal product Lyss Grass. If vaccination is required, immunization should be performed one week after discontinuation of Lyss Grass, 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 Lyss Grass should be postponed. If therapy has already been started, it should be temporarily interrupted until healing of the oral lesions 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 syndrome.

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of specific immunotherapy products in pregnant women are limited, as studies on toxic effects on reproductive function and fetal development 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 fetus associated with the possibility of systemic reactions and the need for medication 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 the medicinal product Lyss Grass during breastfeeding. A harmful effect on the breastfed infant is not expected.

Fertility

Clinical data on the effect of Lyss Grass 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 Grass may have a slight influence on the ability to drive 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 positive results of a specific IgE test to grass 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 provided as an example only.

Dosing

Treatment must be administered under the supervision of a physician experienced in the management 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 actions in such cases, or in the event of safety concerns, the physician may require the first dose to be administered under medical supervision.

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

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

SUPPORTIVE THERAPY

After the initial phase, seasonal treatment is continued by taking 1 tablet of 1000 AU 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.

The 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 at the last tolerated dose.

Children.

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

Overdose.

Adults with grass pollen allergy participated in clinical trials and received the medicinal product at doses up to 2000 AU.

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 swallowing, dyspnea, acute bronchial asthma attack, voice changes, arterial hypotension, or a sensation of lump in the throat, the medicinal product must be discontinued immediately and medical advice should be sought.

Symptomatic treatment is recommended.

Adverse Reactions

The information on adverse reactions presented in the table below is based on data from controlled clinical trials involving adult patients with pollen-induced allergic rhinoconjunctivitis. The data on the frequency of adverse drug reactions are derived from a population of 201 patients who received active treatment.

Adverse reactions are categorized by frequency according to the recommended MedDRA (Medical Dictionary for Regulatory Activities) classification: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), and frequency not known (cannot be estimated from the available data).

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: rhinitis.

Immune system disorders: oral allergy syndrome.

Nervous system disorders: paraesthesia.

Eye disorders: increased lacrimation, allergic conjunctivitis, conjunctival oedema, eyelid oedema, conjunctival hyperaemia, eye pruritus.

Vascular disorders: peripheral vascular disorders.

Respiratory system disorders: bronchospasm, cough, dyspnoea, sneezing, rhinorrhoea, nasal congestion, pharyngeal paraesthesia, laryngeal oedema, pharyngeal oedema, epistaxis.

Gastrointestinal disorders: vomiting, dyspepsia, tongue oedema.

Skin and subcutaneous tissue disorders: urticaria, facial oedema, pruritus, skin rash, erythema, neurodermatitis.

General disorders: mucosal oedema, facial oedema.

Investigations: increased heart rate.

Description of selected adverse reactions

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

In the event of sudden worsening of asthma symptoms or severe systemic reactions, angioneurotic oedema, difficulty in 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 the medicinal product Lais Herbs in children under 5 years of age is not recommended due to the lack of data in this patient group.

Reporting of suspected adverse reactions

After marketing authorization, it is very important to report suspected adverse reactions. This allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any adverse reactions through the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of the 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.

LOPHARMA S.P.A.

Manufacturer's address and place of business.

BOULAVARD KASSALA, 40 - 20143 MILAN (MI), Italy.