Axoglatiran FS - instructions for use, dose, side effects, contraindications

Glatiramer acetate is an acetic acid salt of a mixture of synthetic polypeptides formed by 4 natural amino acids: L-glutamic acid, L-alanine, L- tyrosine and Llysine, and has a chemical structure similar to the main myelin protein.

Glatiramer acetate alters the course of the pathological process in demyelinating central nervous system (CNS) disease - multiple sclerosis, which refers to autoimmune diseases that alter the ratio of T-suppressors in the body. Glatiramer acetate performs immunomodulatory action at the injection site. Its therapeutic effect is mediated through the systemic spread of activated T-suppressors.

Glatiramer acetate has a specific mechanism of action, which is based on the ability to competitively replace myelin antigens - myelin basic protein, myelin oligodendrocyte glycoprotein and proteolipid protein at sites of binding with molecules of the main histocompatibility complex of class II located on antigen-presenting cells. The consequence of competitive displacement is two reactions: stimulation of antigen-specific suppressor T-lymphocytes (Th2-type) and inhibition of antigen-specific effector T-lymphocytes (Th1-type). Activated T-suppressor lymphocytes enter the systemic circulation and penetrate the central nervous system. When entering the site of inflammation in the central nervous system, these T-lymphocytes are reactivated with myelin antigens, which leads to the production of anti-inflammatory cytokines (IL-4, IL-6, IL-10, etc.). These cytokines reduce local inflammation by suppressing the local inflammatory T-cell response, which leads to the accumulation of specific anti-inflammatory cells Th2-type and inhibition of the proinflammatory system Th1-cells.

Besides, glatiramer acetate stimulates the synthesis of the neurotrophic factor Th2-cells and protects brain structures from damage (neuroprotective effect).

Glatiramer acetate does not have a generalized effect on the main links of normal immune reactions of the body, which fundamentally distinguishes it from nonspecific immunomodulators, including interferon-beta preparations.

The resulting antibodies to glatiramer acetate in long-term use do not have a neutralizing effect, which reduces the clinical effect of the drug.

Pharmacokinetics:

Due to the peculiarities of the chemical structure of glatiramer acetate, which is a mixture of polypeptides formed by natural amino acids, as well as a low therapeutic dose, the pharmacokinetics data are only indicative. Based on them, as well as on experimental data, it is believed that after subcutaneous (SC) injection glatiramer acetate quickly hydrolyzed at the injection site. Products of hydrolysis, as well as a small part of unchanged glatiramer acetate can enter the lymphatic system and partially reach the vascular bed.The determined concentration of glatiramer acetate or its metabolites is not correlated with the therapeutic effect.

Indications:

- Clinically isolated syndrome (the only clinical episode of demyelination, suggesting multiple sclerosis) with the severity of the inflammatory process, requiring the use of intravenous glucocorticosteroids (to slow the transition to clinically significant multiple sclerosis).

- relapsing-remitting multiple sclerosis (to reduce the frequency of exacerbations, slow the development of disabling complications).

Contraindications:

- Hypersensitivity to glatiramer acetate or D-mannitol;

- children under 18 years of age (efficacy and safety not studied);

- pregnancy.

Carefully:

Predisposition to the development of allergic reactions, cardiovascular diseases, impaired renal function.

Pregnancy and lactation:

Data on the use of glatiramer acetate during pregnancy are not available, the possible risk of such use during pregnancy is not established. A drug Aksoglatiran® FS contraindicated during pregnancy.

During treatment with the drug Aksoglatiran® FS it is necessary to use reliable methods of contraception.

It is not known whether glatiramer acetate with breast milk, therefore, if you need to use during lactation, you should evaluate the expected benefit of therapy for the mother and the potential risk to the child.

Dosing and Administration:

In the form of subcutaneous injections of 20 mg of drug Axoglatiran® FS (1 syringe filled with injection for injections) once a day, preferably at the same time of day. Treatment is long. The decision to discontinue therapy should be made by the attending physician.

Each syringe with the drug Aksoglatiran® FS is intended for single use only.

Recommendations for patients on the use of the drug Aksoglatiran® FS

Individual packaging with a filled syringe after storage in a refrigerator should be kept at room temperature for at least 20 minutes. When changing the color of the solution or the presence of suspended particles, it should not be used.

The drug is administered subcutaneously, observing the rules of aseptic and antiseptic, changing the injection site daily. The most convenient areas for subcutaneous injection are: the outer surface of the shoulder, anterior-external surface of the thigh, abdomen (about 5 cm around the navel), buttocks.In these places, the skin is easily caught in the fold and the minimal danger of damage to the blood vessels and nerves (in Fig. 1, the injection sites are highlighted in dark).

Do not inject into painful points, discolored, reddened areas of the skin or areas with seals and nodules. You should constantly change injection points inside the injection area to reduce discomfort at the injection site.

Each syringe containing the drug solution is for single use only; The remaining solution of the drug should be destroyed.

Picture 1: Scheme of locations for hypodermic injections.

Administration of the drug

1. Take the syringe out of the individual contour pack.

2. Take the syringe in the hand that you are writing. Remove the protective cap from the needle.

3. Pre-treat the injection site with a cotton swab with alcohol solution, lightly fold the skin into the fold with the thumb and forefinger, as shown in Fig. 2.

Figure 2: Scheme of subcutaneous injection

4. Place the syringe perpendicular to the injection site and insert the needle into the skin at an angle of 90 °, as shown in Fig.3, insert the drug, evenly pressing the syringe plunger down to the end (until it is completely emptied).

Figure 3: Scheme of subcutaneous injection

5. Extract the syringe with the needle vertically upwards, keeping the same angle.

6. Place the syringe in the disposal container.

If you forgot to enter the drug Aksoglatiran® FS, inject immediately as soon as you remember it. Do not administer a double dose of the drug. Use the next syringe with Axoglatiran® FS only after 24 hours.

Side effects:

Glatiramer acetate is safe and well tolerated by patients. In some cases, the following adverse reactions may occur.

From the side of the blood and lymphatic system: lymphadenopathy, leukocytosis, leukopenia, splenomegaly, thrombocytopenia, changes in lymphocyte structure.

From the immune system: hypersensitivity reaction, anaphylactoid reaction, angioedema.

From the endocrine system: hyperthyroidism.

From the side of metabolism: anorexia, weight gain, alcohol intolerance, gout, hyperlipidemia, hypernatremia, decreased ferritin concentration in serum.

From the nervous system: headache, anxiety, depression, euphoria, nervousness, pathological dreams, psychosis, hallucinations, hostility, mania, personality disorder, suicidal behavior, taste perversion, migraine, syncope, tunnel syndrome, cognitive disorders, tremor, convulsions, dysgraphia, dyslexia, violation motor functions, myoclonus, neuritis, neuromuscular blockade, paralysis, including peroneal nerve, stupor.

From the side of the organ of vision: diplopia, visual field defect, eye movement disorder, cataract, corneal damage, dryness of sclera and cornea, subconjunctival hemorrhage, age of ptosis, mydriasis, nystagmus, optic nerve atrophy, visual impairment.

From the side of the organ of hearing and balance: headache, hearing loss.

From the cardiovascular system: heart palpitations, tachycardia, extrasystole, sinus bradycardia, paroxysmal tachycardia, increased blood pressure, varicose veins.

From the respiratory system: cough, shortness of breath, seasonal rhinitis, apnea, hyperventilation of the lungs, laryngospasm.

From the side of the digestive tract: nausea, vomiting, edema of the tongue, constipation, caries, odontogenic periostitis, salivary gland enlargement, dyspepsia, dysphagia, belching, esophageal ulcer, colitis, enterocolitis, polyposis of the large intestine, anorectal disorders, rectal bleeding.

From the liver and biliary tract: cholelithiasis, hepatomegaly. From the skin and subcutaneous tissues: ecchymosis, hyperhidrosis, skin rash, itching, urticaria, contact dermatitis, erythema nodosum, cutaneous nodules.

From the side of the musculoskeletal system and connective tissue: arthralgia, pain in the cervical spine, back pain, arthritis, bursitis, pain in the side, muscle atrophy, osteoarthritis.

From the urinary system: imperative urge to urinate, pollakiuria, urine retention, hematuria, nephrolithiasis.

From the genitals and mammary glands: amenorrhea, mammary gland enlargement, erectile dysfunction, prolapse of pelvic organs, deviation of laboratory parameters in smears from the cervical canal, violation of the menstrual cycle, vulvovaginal disorders.

Infections: otitis media, bronchitis, gastroenteritis, exacerbation of diseases caused by N. simplex, rhinitis, vaginal candidiasis, inflammation of subcutaneous fat, furunculosis, pyelonephritis, herpes zoster.

Other: reactions immediately after the injection *, asthenia, fatigue, chills, fever, nasal bleeding, peripheral edema, a hangover state.

* Reactions immediately after injection

Local Reactions: pain, redness, swelling, abscess, hematoma, lipoatrophy, skin necrosis.

Systemic reactions: "hot flushes" of blood, chest pain, palpitation, anxiety, shortness of breath, difficulty swallowing, hives. These symptoms are temporary and limited and do not require special intervention; they can also begin several months after the initiation of therapy, the patient may experience a symptom occasionally.

Overdose:

Data on drug overdose Axoglatiran® FS no.

In case of an overdose, careful observation and symptomatic treatment are indicated.

Interaction:

The interaction between glatiramer acetate and other drugs has not been adequately studied.

There was no drug interaction,including simultaneous use of glatiramer acetate with drugs that are used to treat multiple sclerosis, including with glucocorticosteroids (with combined use for up to 28 days). Very rarely the frequency of local reactions can increase.

Special instructions:

At the beginning of treatment with the drug Axoglatiran® FS It is necessary to monitor the neurologist and the doctor who has experience in treating multiple sclerosis.

Patients should be informed of the possible occurrence of adverse reactions, including those that occur immediately after injection of the drug Axoglatiran® FS. Most of these symptoms are brief, spontaneously resolved without consequences. If serious adverse reactions develop, stop treatment immediately and consult your doctor or call for emergency medical attention. The decision to use symptomatic therapy is taken by a doctor.

The chest pain that occurs immediately after the injection is usually transient, lasts for several minutes, has no connection with other symptoms, passes by itself without any clinical consequences. The mechanism of development of this symptom is unclear.

With prolonged use (for several months) of the drug Axoglatiran® FS at the injection site, lipoatrophy may develop and, in isolated cases, skin necrosis. In order to prevent the development of these local reactions, it is necessary to recommend the patient strictly follow the sequence of injection sites according to a scheme in which a mandatory daily change in the site for injection should be provided.

Patients with impaired renal function or cardiovascular disease should be under the supervision of a physician.

Due to the fact that the drug Aksoglatiran® FS is an immunomodulatory drug and is used in the treatment of autoimmune disease - multiple sclerosis, its use can be accompanied by changes in the functions of the immune system, therefore, the state of the patient's immune system should be periodically monitored.

Effect on the ability to drive transp. cf. and fur:

Based on the available data, there is no need for special precautions for persons driving a vehicle or complex equipment.

Form release / dosage:

A solution for subcutaneous administration, 20 mg / ml.

Packaging:

1 ml of the solution in sterile syringes of a single use from glass I of hydrolytic class with a glued needle and a protective cap made of polypropylene with a rubber insert.

One filled syringe with the inserted piston is placed in a contour mesh box made of a polyvinylchloride film or PET film coated with aluminum foil or a nonwoven polyethylene material, or medical or uncoated paper.

1 contour pack with a filled syringe in a pack of cardboard.

28 or 30 packs with one syringe together with instructions for use in a pack (consumer packaging) of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 8 ° C.

Do not freeze.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003572

Date of registration:18.04.2016 / 30.09.2016

Expiration Date:18.04.2021