Alksoyd (mixture of polymerized allergen extracts)

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALXOID (mixture of polymerized allergen extracts)

Composition:

Active substances: 1 ml of suspension contains 2000 TU (bottle A for initial treatment) or 10,000 TU (bottle B for initial/maintenance treatment) of glutaraldehyde-polymerized extract mixture:

mixture of allergens from house dust mites (Dermatophagoides pteronyssinus 50%, Dermatophagoides farinae 50%), or

mixture of allergens from velvet grass (Holcus lanatus), orchard grass (Dactylis glomerata), perennial ryegrass (Lolium perenne), timothy grass (Phleum pratense), Kentucky bluegrass (Poa pratensis), meadow fescue (Festuca pratensis), or

mixture of allergens from common barley (Hordeum vulgare), cultivated oat (Avena sativa), rye (Secale cereale), soft wheat (Triticum aestivum), or

mixture of allergens from silver birch (Betula pendula 25%), black alder (Alnus glutinosa 25%), common ash (Fraxinus excelsior 25%), common hazel (Corylus avellana 25%), or

mixture of allergens from timothy grass (Phleum pratense 50%), silver birch (Betula pendula 50%), or

mixture of allergens from timothy grass (Phleum pratense 34%), ragweed (Ambrosia artemisiifolia 33%), common mugwort (Artemisia vulgaris 33%), or

mixture of allergens from ragweed (Ambrosia artemisiifolia 50%), common mugwort (Artemisia vulgaris 50%).

Excipients: phenol, sodium chloride, aluminum hydroxide gel, water for injections. Concentration is expressed in therapeutic units (TU).

Pharmaceutical form. Suspension for subcutaneous administration.

Pharmacotherapeutic group. Miscellaneous agents. Allergens, allergen extracts.

ATC code V01A A.

Pharmacological Properties

Subcutaneous immunotherapy increases tolerance to allergens through immunological mechanisms. This method of allergen-specific therapy persistently reduces the level of immunoglobulin E (IgE) in human serum and also prevents seasonal increases in IgE levels caused by the natural rise in certain allergens during specific periods of the year.

Pharmacodynamics

Mechanism of action. ALKOID (a mixture of polymerized allergen extracts) is used to treat patients with specific IgE-mediated allergic reactions to various allergens, presenting with symptoms such as rhinitis and rhinoconjunctivitis. The pharmacodynamic target is the immune system. The objective of the medicinal product is to modify the immune response to the allergens to which the patient is exposed. The complete and detailed mechanism of action in terms of the clinical effect of specific immunotherapy is not fully understood and has not been thoroughly investigated. Administration of the medicinal product ALKOID (a mixture of polymerized allergen extracts) induces a systemic competitive antibody response to various allergens, accompanied by a gradual increase in the production of specific IgG over 2 years of treatment and beyond. The clinical significance of this observation has not been established.

Pharmacokinetics

With the specified route of administration, significant systemic absorption into the bloodstream is not expected for the medicinal product ALKOID (a mixture of polymerized allergen extracts). Therefore, no pharmacokinetic studies in animals or clinical studies on the pharmacokinetic profile and metabolism have been conducted.

Preclinical Safety

Preclinical studies do not indicate any particular risk associated with the use of the medicinal product at therapeutic doses according to the instructions for medical use.

Clinical Characteristics

Indications

The medicinal product ALKSOID (a mixture of polymerized allergen extracts) is indicated for allergen-specific immunotherapy in the treatment of allergic rhinitis and rhinoconjunctivitis.

Immunotherapy can be administered to adults and children aged 5 years and older.

Contraindications

Hypersensitivity to the components of the medicinal product (see section "Composition").

Concomitant use of β-blockers.

Elevated body temperature (above 38.5 °C).

Active infectious diseases (viral hepatitis, tuberculosis, pneumonia, mononucleosis, etc.).

Acquired immunodeficiency syndrome (AIDS).

Poorly controlled or partially controlled bronchial asthma.

If the patient has active infectious diseases (pneumonia, hepatitis, mononucleosis, etc.), initiation of treatment with the medicinal product should be postponed until the infection is resolved.

Any autoimmune systemic disease: immunodeficiency or malignant disease. Pregnancy.

Special Precautions

No special warnings or precautions are required for the use of 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 Types of Interactions

Do not use concomitantly with β-blockers.

Data on possible risks of concomitant immunotherapy with other allergens during the use of this medicinal product are lacking.

Special precautions for use

The medicinal product ALKSOID (a mixture of polymerized allergen extracts) must be prescribed exclusively by an allergist and administered under the physician's supervision (self-administration of the medicinal product by patients is strictly prohibited).

ALKSOID (a mixture of polymerized allergen extracts) should be used with caution in patients with autoimmune diseases in remission.

It is recommended to avoid any intense physical exertion for 1–2 hours after administration of the medicinal product.

Important information on excipients

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e. it is practically sodium-free.

This medicinal product contains substances that may cause allergic reactions, systemic and/or local adverse reactions in patients.

The suspension contains a suitable concentration of a mixture of polymerized extracts adsorbed onto aluminium hydroxide gel, suspended in an isotonic physiological 4% phenol solution.

Use during pregnancy or breastfeeding

Pregnancy

Currently, there are no reliable data on the use of the medicinal product ALKSOID (a mixture of polymerized allergen extracts) in pregnant women. Therefore, the medicinal product is contraindicated during pregnancy. If pregnancy occurs during ongoing treatment, the decision to discontinue the medicinal product should be based on a complete assessment of the patient’s overall condition, including pulmonary function, and reactions to previous administrations of ALKSOID (a mixture of polymerized allergen extracts). Close monitoring of pregnant patients with bronchial asthma is recommended.

Breastfeeding

There are no clinical data on the use of the medicinal product ALKSOID (a mixture of polymerized allergen extracts) during breastfeeding. No effects on breastfed infants are expected.

Ability to influence the speed of reactions when driving or operating machinery

The effect of allergen preparations on the ability to drive or operate machinery is absent or negligible.

Method of Administration and Dosage

Dosage Regimen

Suspension for subcutaneous administration. Injections must be administered only by a healthcare professional. Typical treatment regimens are outlined below. The exact treatment schedule should be determined by a physician.

Initial Treatment

For treatment, one vial A and/or one or two vials B are required. Treatment begins with the suspension from vial A (2000 TU/ml). Initially, a dose of 0.2 ml is administered, followed by a second dose of 0.5 ml one week later. After the 0.5 ml dose (maximum dose) from vial A (concentration 2000 TU/ml), treatment continues one week later with the suspension from vial B (concentration 10,000 TU/ml): initially 0.2 ml from this vial is administered, followed by a dose of 0.5 ml one week later. After the 0.5 ml dose (maximum dose) from vial B (concentration 10,000 TU/ml), the suspension from this vial is administered once monthly at a dose of 0.5 ml until the solution in the vial is used up.

Before completing administration of the suspension from the last vial, it is necessary to consult a physician to obtain the medicinal product intended for maintenance therapy.

Table 1

Initial Treatment Schedule

Supportive treatment

For treatment, 1 or 2 vials of B are required. Treatment is initiated with a dose of 0.5 mL from vial B once a month. A total of 5 doses are administered from this vial.

Before the suspension from the last vial is completely used, it is necessary to consult a physician to obtain the medicinal product intended for supportive treatment.

Table 2

Supportive treatment regimen

Pediatric patients

For children aged 5 years and older, the recommended doses of the medicinal product ALKSOID (a mixture of polymerized allergen extracts) are the same as for adults.

Method of administration

Standard precautions for use and handling of medicinal products
The medicinal product ALKSOID (a mixture of polymerized allergen extracts) is intended for use in a hospital setting.

The medicinal product ALKSOID (a mixture of polymerized allergen extracts) must be administered only by an experienced physician.

The medicinal product must be administered subcutaneously.

Administration of the medicinal product ALKSOID (a mixture of polymerized allergen extracts) must be carried out only in a medical facility equipped with emergency medical equipment for managing anaphylactic shock. In particular, epinephrine and equipment for cardiopulmonary resuscitation must be available.

Procedure for administering the medicinal product from vials:

• Ensure a high level of aseptic technique when handling vials;
• Use 1 mL syringes (insulin syringes) with 5/10 or 6/10 needles (1 cm in length) for the procedure;
• Gently shake the vial to ensure the medicinal product becomes homogeneous;
• Disinfect the rubber stopper of the vial with alcohol and insert the needle;
• Before administering the medicinal product, disinfect the injection site—the outer surface of the upper arm (deltoid muscle)—with alcohol, pinch the skin to form a skin fold to prevent blood from entering the syringe;
• After administration of the medicinal product, do not rub the skin area where the injection was given.

The rubber stopper should not be punctured more than once in the same spot to avoid contamination of the suspension with rubber particles or even loss of self-sealing properties.

The patient must remain at the medical facility for at least 30 minutes after the injection so that, if any adverse reactions occur, immediate medical assistance can be provided.

Children

The medicinal product may be used in children aged 5 years and older.

Overdose

Exceeding the dose of allergens administered to a patient during allergen-specific immunotherapy may lead to the development of systemic and local adverse reactions (see section "Adverse Reactions").

Side effects

Most adverse reactions associated with the use of the medicinal product ALK-OID (a mixture of polymerized allergen extracts) occur rarely or very rarely. They may be local (at the site of administration) or systemic.

Mild to moderate local allergic reactions (redness, pain and/or swelling at the injection site) may occur from 30 minutes to 72 hours after injection (see section "Special precautions for use").

The presence of these adverse effects does not necessarily mean that treatment must be discontinued or postponed, but monitoring during administration may be required.

There have been isolated reports of severe acute worsening of asthma symptoms. In such cases, treatment should be discontinued, and it is strongly recommended to inform the physician.

Patients with known risk factors should not initiate treatment with ALK-OID (a mixture of polymerized allergen extracts) (see section "Contraindications").

Possible adverse reactions

All adverse reactions are listed by system organ class and frequency of occurrence: very common (≥ 1/10), common (≥ 1/100 – < 1/10), uncommon (≥ 1/1000 – < 1/100), rare (≥ 1/10,000 – < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

Immune system disorders: common – hypersensitivity; very rare – anaphylactic reaction* and anaphylactic shock*.

Nervous system disorders: very rare – dizziness, headache, tremor.

Eye disorders: uncommon – conjunctivitis; very rare – conjunctival swelling.

Ear and labyrinth disorders: very rare – tinnitus.

Cardiac disorders: rare – disorders of the cardiovascular system; very rare – tachycardia.

Vascular disorders: uncommon – arterial hypotension; very rare – hypertensive crisis, pallor.

Respiratory, thoracic and mediastinal disorders: uncommon – bronchospasm, cough, dyspnea, nasal congestion, rhinitis, rhinorrhea, sneezing; rare – bronchial asthma, bronchial obstruction; very rare – bronchial hyperreactivity, dysphonia, throat and larynx irritation, nasal and oropharyngeal discomfort, nasopharyngitis, oropharyngeal pain, sensation of throat numbness, pharyngitis, rapid breathing, wheezing.

Gastrointestinal disorders: uncommon – nausea; very rare – gastrointestinal disorders, diarrhea, swallowing difficulty, vomiting.

Skin and subcutaneous tissue disorders: common – pruritus; uncommon – skin reaction; very rare – angioneurotic edema, dermatitis, erythema, hyperhidrosis, abnormal hair growth, papule, pemphigoid, rash, skin discoloration, skin nodule, urticaria.

Musculoskeletal and connective tissue disorders: very rare – limb discomfort, myalgia.

General disorders and administration site conditions: common – local reaction; uncommon – fatigue, injection site induration, malaise, pain; rare – swelling; very rare – asthenia, chest discomfort, feeling of warmth, granuloma, inflammation, injection site reaction (including cyst and edema), edema, sensation of warmth, foreign body sensation, feeling of depression.

Investigations: very rare – increased body temperature; very rare – increased blood pressure.

If a patient experiences serious adverse reactions to treatment, consideration should be given to using antiallergic medicinal products.

*Severe systemic reactions, included in the concept of anaphylaxis, may lead to anaphylactic shock. In case of anaphylactic reaction, intramuscular administration of adrenaline is required at a dose of: 0.01 mg/kg body weight, maximum 0.5 mg (solution 1/1000). Administration may be repeated after 5–15 minutes.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after medicinal product authorization is of great importance. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua

Shelf life

3 years.

Storage conditions

Store in the original packaging in a dark place.

Store in a refrigerator (at 2–8 °C). Do not freeze.

Keep out of reach of children.

Packaging

2.5 ml in a vial.

Primary packaging: a vial made of clear type I glass with a butyl rubber stopper, sealed with a silver-colored cap (vials A 2000 TO for initial treatment) or blue cap (vials B 10000 TO for maintenance treatment).

Secondary packaging: 2 vials sealed with silver-colored caps (vials A 2000 TO for initial treatment) and blue caps (vials B 10000 TO for maintenance treatment), or 1 vial sealed with a blue cap (vials B 10000 TO for maintenance treatment), placed in a white, impact-resistant plastic box filled with foam material into which the vials containing the medicinal product are inserted.

Prescription status

Prescription only.

Manufacturer

INMUNOTEC, S.L.

Manufacturer's address and place of business

Calle Punto Mobi, 5, Alcalá de Henares, 28805 Madrid, Spain