Description
Pharmacological action
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-alanine lysine and the chemical structure has elements of similarity with the main myelin protein.
Glatiramer acetate changes the course of the pathological process in demyelinating disease of the central nervous system (CNS) – multiple sclerosis, which refers to autoimmune diseases that change the ratio of T-suppressors in the body. Glatiramer acetate provides an immunomodulatory effect 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 – the main myelin protein, myelin oligodendrocyte glycoprotein and proteolipid protein at the sites of binding to the molecules of the main histocompatibility complex of class 2 located on antigen-presenting cells.
The consequence of competitive crowding out 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. Once in the CNS inflammation site, these T-lymphocytes are reactivated by myelin antigens, which leads to their production of anti-inflammatory cytokines (including IL-4, IL-6, IL-10), which reduce local inflammation by suppressing the local inflammatory T-cell response. This leads to the accumulation of specific anti-inflammatory Th2-type cells and inhibition of the pro-inflammatory Th1-cell system.
In addition, glatiramer acetate stimulates the synthesis of the neurotrophic factor by Th2-type cells and protects the brain structures from damage (neuroprotective effect). Glatiramer acetate does not have a generalized effect on the main links of normal body immune responses, which fundamentally distinguishes it from non-specific immunomodulators, including beta-interferon preparations. The resulting antibodies to glatiramer acetate with prolonged use do not have a neutralizing effect, reducing 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 are only indicative. Based on them, as well as on experimental data, it is believed that after subcutaneous administration, the drug is rapidly hydrolyzed at the injection site. The products of hydrolysis, as well as an insignificant part of the unchanged glatiramer acetate, can enter the lymphatic system and partially reach the vascular bed. The determined concentration of glatiramer acetate or its metabolites in the blood does not correlate 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 down the transition to clinically significant multiple sclerosis)
– relapsing-scared for reducing slowing down the development of disabling complications).
Contraindications
– Hypersensitivity to glatiramer acetate or mannitol
– pregnancy srd lkp – children under 18 years of age (due to lack of data on efficacy and safety).
Caution: – For patients predisposed to allergic reactions and with cardiovascular diseases
– patients with impaired renal function should regularly monitor laboratory parameters.
Special instructions
Patients should be informed of possible adverse reactions associated with the use of the drug.
At the beginning of treatment with Glatirat, control by a neurologist and a doctor with experience in treating multiple sclerosis is necessary.
Patients should be informed of the possibility of adverse reactions, including those that occur immediately after injection of the drug Glatirat. Most of these symptoms are short-lived, resolve spontaneously without consequences. If serious adverse reactions develop, you should immediately discontinue therapy and consult your doctor or call an ambulance. The decision to use symptomatic therapy is made by the doctor.
Chest pain that occurs immediately after injection (see section Side effects), as a rule, is transient in nature, lasts several minutes, has no connection with other symptoms, and resolves on its own without any clinical consequences. The mechanism for the development of this symptom is unclear.
With prolonged use (for several months) of the drug Glatirat at the injection sites, lipoatrophy can develop and in rare cases skin necrosis. In order to prevent the development of these local reactions, it is necessary to recommend that the patient strictly observe the sequence of injection sites according to the scheme, which must provide for a mandatory daily change in the injection site.
Patients with impaired renal function or cardiovascular disease should be monitored by a physician.
Due to the fact that the drug Glatirat is an immunomodulating drug and is used in the treatment of an autoimmune disease – multiple sclerosis, its use may be accompanied by changes in the functions of the immune system, in this connection, the state of the patient s immune system should be periodically monitored.
If the patient does not have the ability to store syringes with the drug Glatirat in the refrigerator, then storage at a temperature of 15-25 ° C, but not more than one month, is allowed.
Impact on the ability to drive transp. Wed and fur .:
Based on the available data, there is no need for special precautions for persons driving a car or complex machinery.
Composition of
1 ml of solution contains:
active ingredient: glatiramer acetate – 20 mg
excipients: mannitol – 40 mg, water for injection – up to 1 ml.
Dosage and administration
The recommended dose for adults 18 years and older is 20 mg of glatiramer acetate (contained in one injection syringe), subcutaneously once a day, preferably at the same time, for a long time.
The decision on the duration of therapy should be made by the attending physician on an individual basis.
If you forgot to give the injections on time, you should administer the drug as soon as you remember about it, but you should not double the dose. Enter the next dose on schedule only after 24 hours.
An immediate post-injection reaction may develop after injection.
Side effects
The drug Glatirat is safe and well tolerated by patients. In some cases, the following adverse reactions may occur. The frequency of adverse reactions is classified as follows: very often (> 1/10) often (> 1/100, but <1/10): infrequently (> 1/1000, but <1/100) rarely (> 1/10000, but <1/1000). Infections and infestations: very often – infections, flu often – bronchitis, gastroenteritis, otitis media, Herpes simplex, rhinitis, periodontal abscess, vaginal candidiasis * infrequently – abprocess, inflammation of the subcutaneous fat, furunculosis, pyelonephritis, Herpes zoster. Neoplasms, including polyps and cysts: often – benign skin neoplasms, neoplasms infrequently – skin cancer. From the hemopoietic and lymphatic systems: often – lymphadenopathy * infrequently – leukocytosis, leukopenia, splenomegaly, thrombocytopenia, changes in the morphology of lymphocytes. From the side of the immune system: often – hypersensitivity reactions. From the endocrine system: infrequently – goiter, hyperthyroidism. From the side of metabolism and nutrition: often – anorexia, weight gain * infrequently – intolerance to alcohol, gout, hyperlipidemia, hypernatremia, decreased serum ferritin concentration. Mental disorder: very often – anxiety *, depression often – nervousness infrequently – unusual dreams, psychosis, euphoria, hallucinations, aggressiveness, mania, personality disorders, suicidal attempts. From the nervous system: very often – headache often – taste perversion, muscle hypertonicity, migraine, speech disorders, fainting, tremors * infrequently – carpal tunnel syndrome, cognitive disorders, cramps, dysgraphia, dyslexia, dystonia, impaired motor function, myoclonus . neuritis, neuromuscular blockade, nystagmus, paralysis, peroneal nerve palsy, stupor, visual field defect. On the part of the organs of vision: often – diplopia, visual impairment * infrequently – cataracts, damage to the cornea, dry sclera and cornea, hemorrhage in the eye, ptosis of the eyelids. mydriasis, optic atrophy. On the part of the organs of hearing and balance: often – hearing impairment. From the cardiovascular system: very often – vasodilation * often – palpitations *, tachycardia * infrequently – extrasystole, sinus bradycardia, paroxysmal tachycardia, increased blood pressure, varicose veins. From the respiratory system: very often – shortness of breath * often – cough, seasonal rhinitis infrequently – apnea, suffocation, nosebleeds, hyperventilation of the lungs, laryngospasm, pulmonary disorders. From the gastrointestinal tract: very often – nausea * often – rectal disorders, constipation, caries, dyspepsia, dysphagia, fecal incontinence, vomiting * infrequently – colitis, enterocolitis, colon polyposis, belching, esophageal ulcer, periodontitis, rectal bleeding, increased salivary glands. From the liver and biliary tract: often – deviation of liver function tests infrequently – gallstone disease, hepatomegaly. From the side of the skin and subcutaneous fat: very often – a skin rash often – ecchymosis, hyperhidrosis, skin itching, skin diseases *, urticaria infrequently – angioedema, contact dermatitis, erythema nodosum, skin nodules. From the side of the musculoskeletal system and connective tissue: very often – arthralgia, back pain * often – neck pain infrequently – arthritis, bursitis, side pain, muscle atrophy, osteoarthritis. From the side of the kidneys and urinary system: often – imperative urges, pollakiuria. urinary retention infrequently – hematuria, nephrolithiasis, diseases of the urinary tract, deviations from laboratory standards for urine analysis. Pregnancy. postpartum and perinatal conditions: infrequently – spontaneous abortion. From the genitals and mammary gland: infrequently – breast engorgement, erectile dysfunction, pelvic organ prolapse, priapism, prostate diseases, deviation of laboratory parameters in smears from the cervical canal, testicular dysfunction, vaginal bleeding, vulvovaginal disorders. Other: very often – asthenia, chest pain *, reactions at the injection site ***, pain * often – chills *, swelling of the face *, atrophy at the injection site ***, local reactions *, peripheral edema, edema, fever infrequently – hypothermia, immediate post-injection reaction, inflammation, cyst, hangover, diseases of the mucous membranes, post-vaccination syndrome, necrosis at the injection site. * The likelihood of such cases in patients taking Glatiramer acetate is more than 2% (> 2/100) compared with the placebo group. An unsigned unsigned reaction * indicates a difference of less than or equal to 2%.
** Reactions at the injection site (various species) include any adverse events that occur at the injection site, with the exception of atrophy and necrosis, which are listed separately.
*** Refers to localized lipoatrophy at the injection site.
In patients with multiple sclerosis who received Glatiramer acetate during uncontrolled clinical trials, as well as during post-marketing use, rare (> 1/10 000, but <1/1000) cases of anaphylactoid reactions were recorded. Storage conditions Store in the original packaging in a dark place at a temperature of 2 to 8 ° C (in the refrigerator). Do not freeze. Keep out of the reach of children. Shelf life 3 years. Do not use after expiration date. active substance Glatiramer acetate Terms of release from drugstores by prescription lekarstvennaja form Solution for