Lays ambrosia

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LAIS AMBROSIA

Composition:

Active substances: chemically modified allergen extract of ragweed pollen:

short ragweed 100% (Ambrosia artemisiifolia 100%);

one 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 a specific immunotherapeutic agent.

Pharmaceutical form. Sublingual tablets.

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

Pharmacotherapeutic group.

Allergens. Allergen extracts. ATC code V01A A.

Pharmacological Properties

Lyss Ambrosia is an agent for specific immunotherapy based on the use of chemically modified allergen extracts. Chemical modification involves carbamylation reaction under alkaline conditions. This procedure ensures:

• modification of epitopes responsible for IgE binding of allergenic components of the extract, as evidenced by a significant reduction in allergenic activity (allergenicity) determined by the EAST (enzyme allergosorbent test)-inhibition method, thereby improving the safety profile;
• preservation of 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 dispersion.

Pharmacodynamics

Specific sublingual immunotherapy is a treatment method involving repeated sublingual administration of specific allergens to modify the immune response to allergens in patients suffering from diseases in which pathological allergic reaction is 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 associated with a significant influence on IgE-mediated inflammatory reactions related to the natural impact of allergens. It has also been demonstrated that specific sublingual immunotherapy leads to a significant reduction in IgE-mediated inflammation, as evidenced 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 mechanisms, 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 Lyss Ambrosia leads to a significant reduction in allergen-specific cellular proliferation in the human body while simultaneously enhancing allergen-specific innate immunity. In particular, Lyss Ambrosia promotes a shift from Th2-type immune response (typical for allergic inflammation) to 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 Lyss Ambrosia is associated with the induction of immunological tolerance to allergens responsible for allergic sensitization.

Pharmacokinetics

The pharmacokinetic properties of Lyss Ambrosia have not been studied due to the characteristics of the active substance (an extract, natural or allergoid, consisting of a mixture of various components). On the other hand, some components are recognized as major allergens. These can be purified and used in pharmacokinetic studies, which could provide useful information. For this purpose, 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 lymphatic tissues; absorption into blood plasma begins 30 minutes after administration and reaches plateau levels within 2 hours. Only in the case of allergoids can intact molecules be detected in blood serum, whereas 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 (Parietaria judaica) (Par j1). Since differences in biological distribution profiles of various allergens administered via oral mucosa are not expected, a similar pattern is likely to occur with the use of allergoids of the major allergens (Amb a1) of ragweed pollen.

Clinical characteristics.

Indications.

Treatment of ragweed 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 detection of specific IgE to ragweed pollen.

Contraindications.

• Hypersensitivity to any component of the medicinal product.
• Presence of malignant neoplasm.
• Autoimmune disease, immune deficiency, immunodeficiency, or immunosuppression.
• Chronic inflammatory disease.
• Acute inflammation in the oral cavity with severe symptoms.
• Target organ pathology (e.g., cardiac or vascular 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 in which epinephrine use is contraindicated.

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 forms of interaction.

No studies on interactions with other medicinal products have 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 regarding possible interactions between the medicinal product Lais Ambrosia and immunosuppressive agents; therefore, as a precautionary measure, 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 Ambrosia.

Special precautions for use

Any local (e.g., oral or lip itching) and/or systemic (e.g., generalized pruritus, urticaria, skin rashes, nausea, cough, rhinorrhea or nasal congestion, general discomfort, or restlessness/anxiety) adverse events 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 must 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 severe 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 Lyss Ambrosia 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 Lyss Ambrosia. Dose reduction of asthma control medications 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 administration of antiviral or antibacterial vaccination during therapy with the medicinal product Lyss Ambrosia. If vaccination is required, immunization should be performed one week after discontinuation of Lyss Ambrosia, 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 or loss, initiation of therapy with Lyss Ambrosia should be postponed. If therapy has already been started, it should be temporarily interrupted until oral lesions have healed.

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 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 Ambrosia during breastfeeding. No effect on the breastfed infant is expected.

Fertility

There are no clinical data on the effect of Lyss Ambrosia on fertility.

Ability to affect reaction speed when driving or operating machinery

As with other medicinal products used in specific immunotherapy, fatigue may occur. Lyss Ambrosia may have a minor 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 ragweed 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 advised by the physician. To ensure proper patient training in the administration of the medicinal product and to facilitate communication between physician and patient regarding potential adverse reactions and necessary actions in response to such events, or in case of safety concerns, the physician may require that the first dose be administered under medical supervision.

Treatment may be initiated at least 3 months before the expected start of the ragweed 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 AU daily, 1–5 times per week (for example, 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 adjustment of the dosing regimen. Therapy should be resumed starting from the last tolerated dose.

Children.

The use of Lais ambrosia in children under 5 years of age is not recommended due to lack of safety and efficacy data in this pediatric population.

Overdose.

Adults with ragweed 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 in swallowing, breathing difficulties, 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.

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 ragweed-induced rhinoconjunctivitis. The data on the frequency of adverse drug reactions are derived from a total of 92 patients who received active treatment.

Adverse reactions were classified according to frequency using MedDRA (Medical Dictionary for Regulatory Activities) categories: 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).

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.

Respiratory system: bronchial disorders.

Skin and subcutaneous tissues: blistering, urticaria.

Gastrointestinal tract: change in coloration of the oral mucosa.

Description of individual adverse reactions

If a significant adverse reaction occurs during therapy, the patient should immediately inform the physician. Depending on the severity of the clinical picture, it may be necessary to consider interrupting therapy, adjusting the dose, and, if required, 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 the product Lais Ambrosia in children under 5 years of age is not recommended, as data for this patient group are lacking.

Reporting suspected adverse reactions

After marketing authorization of a medicinal product, it is very important to report suspected adverse reactions. This enables continuous monitoring of the benefit-risk balance associated with the use 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 reach of children.

Packaging.

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

sublingual tablets No. 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 its business premises.

VIA CASALBA, 40 - 20143 MILAN (MI), Italy.