Methypredum

General characteristics. Structure:

Active agent: Methylprednisolonum - 4 or 16 mg;

excipients: lactoses monohydrate, starch corn, magnesium stearate, gelatin, talc, the water purified.

Contains in 1 bottle:

active agent: sodium Methylprednisolonum succinate in recalculation on Methylprednisolonum - 250 mg; excipients: sodium hydroxide. Solvent - water for injections.

Description: lyophilisate for preparation of solution for intramuscular and intravenous administration: the lyophilized powder of white or slightly yellowish color, hydroscopic.
Solvent (water for injections) - transparent colourless liquid.

Tablets of 4 mg - tablets, round, flat with slanted edge, from almost white till white color with cross dividing risky on one party. Tablets of 16 mg - tablets, round, flat with slanted edge, from almost white till white color with cross dividing risky and the put ORN 346 code on one party.

Pharmacological properties:

Pharmacodynamics. Methylprednisolonum - synthetic glucocorticosteroid drug. Has an antiinflammatory, antiallergic, immunodepressive effect, increases sensitivity of beta adrenoceptors to endogenous catecholamines. Interacts with specific cytoplasmatic receptors (receptors for glucocorticosteroids (GKS) are in all fabrics, especially their is a lot of in a liver) with formation of the complex inducing formation of proteins (including the enzymes regulating the vital processes in cells).

Protein metabolism: reduces amount of globulins in plasma, increases synthesis of albumine in a liver and kidneys (with increase in coefficient albumine/globulin), reduces synthesis and strengthens a protein catabolism in muscular tissue.

Lipidic exchange: increases synthesis of higher fatty acids and triglycerides, redistributes fat (accumulation of fat happens preferential in the field of a shoulder girdle, the person, a stomach), leads to development of a hypercholesterolemia.

Carbohydrate metabolism: increases absorption of carbohydrates from digestive tract; increases activity of glyukozo-6-phosphatase (increase in intake of glucose from a liver in blood); increases activity of a fosfoenolpiruvatkarboksilaza and synthesis of aminotransferases (activation of a gluconeogenesis); promotes development of a hyperglycemia.

Water and electrolytic exchange: detains sodium and water in an organism, stimulates potassium removal (minerapokortikoidny activity), reduces absorption of calcium from digestive tract, reduces a mineralization of a bone tissue.

The antiinflammatory effect is connected with release oppression by eosinophils and mast cells of mediators of an inflammation; induction of formation of lipokortin and reduction of quantity of the mast cells producing hyaluronic acid; with reduction of permeability of capillaries; stabilization of cellular membranes (especially lizosomalny) and membranes of organellas. Affects all stages of inflammatory process: inhibits synthesis of prostaglandins at the level of arachidonic acid (липокортин oppresses A2 phospholipase, suppresses a liberation of arachidonic acid and inhibits biosynthesis of endoperoxides, the leukotrienes promoting processes of an inflammation, an allergy, etc.), synthesis of "pro-inflammatory cytokines" (Interlaken 1, a tumor necrosis factor an alpha, etc.); increases resistance of a cellular membrane to action of various disturbing factors.

The immunodepressive effect is caused by the caused involution of an adenoid tissue, oppression of proliferation of lymphocytes (especially T lymphocytes), suppression of migration of V-cells and interactions of T - and V-lymphocytes, braking of release of cytokines (interleykina-1,2; gamma interferon) from lymphocytes and macrophages and decrease in antibody formation.

The antiallergic effect develops as a result of decrease in synthesis and secretion of mediators of an allergy, braking of release from sensitized mast cells and basophiles of a histamine, etc. biologically active agents, reduction of number of the circulating basophiles, T - and V-lymphocytes, mast cells; suppression of development of adenoid and connecting tissue, decrease in sensitivity of effector cells to mediators of an allergy, oppression of antibodyformation, change of an immune response of an organism.

At obstructive respiratory diseases action is caused, mainly, by braking of inflammatory processes, the prevention or reduction of expressiveness of hypostasis of mucous membranes, decrease in eosinophilic infiltration of a submucosal layer of an epithelium of bronchial tubes and adjournment in mucous bronchial tubes of the circulating cell-bound immune complexes, and also braking of an erozirovaniye and desquamation mucous. Increases sensitivity of beta adrenoceptors of bronchial tubes of small and average caliber to endogenous catecholamines and exogenous sympathomimetics, reduces viscosity of slime due to reduction of its products.

Suppresses synthesis and secretion of adrenocorticotropic hormone (AKTG) and for the second time - synthesis of endogenous GKS.

Slows down connective tissue reactions during inflammatory process and reduces a possibility of formation of cicatricial fabric.

Pharmacokinetics. At intake it is quickly soaked up, absorption makes more than 70%. Has effect of "the first passing".

At intramuscular introduction absorption - full and rather bystry. Bioavailability at intramuscular introduction - 89%.

Time of achievement of the maximum concentration in a blood plasma (Cmax) after intake of-1,5 h, at intramuscular introduction - 0,5-1 hours of Cmax after intravenous administration in a dose of 30 mg/kg within 20 minutes, or intravenous drop administration in a dose of 1 g within 30-60 minutes, reaches 20 mkg/ml. After intramuscular introduction of 40 mg approximately in 2 hours Cmax making 34 mkg/ml is reached.

Communication with proteins of plasma - 62% irrespective of the entered dose (contacts only albumine).

Plasma elimination half-life of blood at oral administration makes about 3,3 hours, at parenteral administration - 2,3-4 hours also probably do not depend on a way of introduction. Due to intracellular activity the expressed distinction between Methylprednisolonum elimination half-life from a blood plasma and in general comes to light biological half-life (about 12-36 hours). Pharmakoterapevtichesky action remains even then when any more drug level in blood is not defined.

It is metabolized preferential in a liver, metabolites (11-keto and 20 oxycompounds) have no GKS-activity and are removed preferential by kidneys (about 85% of the entered dose are found within 24 hours in urine, and about 10% - in Calais). Gets through a blood-brain barrier and a placental barrier. Metabolites are found in maternal milk.

Indications to use:

- General diseases of connecting fabric (system lupus erythematosus, scleroderma, nodular periarteritis, dermatomyositis, pseudorheumatism).
- Acute and chronic inflammatory diseases of joints - gouty and psoriasis arthritis, an osteoarthritis (including posttraumatic), polyarthritis (including senile), the humeroscapular periarthritis ankylosing a spondylarthritis (Bekhterev's disease), juvenile arthritis, Stillau's syndrome of adults, a bursitis nonspecific tendosinovit, a synovitis and an epicondylitis.
- Acute rheumatism, rheumatic carditis, hysterical chorea.
- Bronchial asthma, asthmatic status.
- Acute and chronic allergic diseases - including allergic reactions to medicines and foodstuff, a serum disease, a small tortoiseshell, allergic rhinitis, a Quincke's edema, a medicinal dieback, a pollinosis, etc.
- Skin diseases - a pemphigus, psoriasis, eczema, atopic dermatitis (widespread neurodermatitis), contract dermatitis (with defeat of a big surface of skin), a toxidermia, seborrheal dermatitis, exfoliative dermatitis, a toxic epidermal necrolysis (Lyell's disease), violent herpetiform dermatitis, Stephens-Johnson's syndrome.
- Wet brain (including against the background of a tumor of a brain or connected with surgical intervention, radiation therapy or an injury of the head) after preliminary parenteral use of GKS.
- Allergic diseases of eyes - allergic forms of conjunctivitis.
- Inflammatory diseases of eyes - a sympathetic ophthalmia, heavy slow lobbies and back uveites, an optic neuritis.
- Primary or secondary adrenal insufficiency (including a state after removal of adrenal glands).
- Inborn adrenal struma.
- Diseases of kidneys of autoimmune genesis (including acute glomerulonephritis).
- Nephrotic syndrome.
- Subacute thyroiditis.
- Diseases of blood and system of a hemopoiesis - an agranulocytosis, a panmyelopathia, autoimmune hemolitic anemia, lympho-and myeloid leukoses, лимфогрануломатоз, a Werlhof's disease, secondary thrombocytopenia at adults, an eritroblastopeniya (erythrocyte anemia), inborn (erythroidal) hypoplastic anemia.
- Intersticial diseases of lungs - an acute alveolitis, a pneumosclerosis, a sarcoidosis of the II-III St.
- Tubercular meningitis, a pulmonary tuberculosis, aspiration pneumonia (in a combination to specific chemotherapy).
- A berylliosis, Leffler's syndrome (which is not giving in to other therapy); lung cancer (in a combination with cytostatics).
- Multiple sclerosis.
- Ulcer colitis, disease Krone, local enteritis.
- Hepatitis, hypoglycemic states.
- Prevention of reaction of graft rejection at organ transplantation.
- A hypercalcemia against the background of oncological diseases, nausea and vomiting when performing cytostatic therapy.
- Multiple myeloma. Parenterally

The emergency therapy at the states demanding bystry increase in concentration of glucocorticosteroids in an organism:

- Depressed cases (burn, traumatic, operational, toxic, cardiogenic) - at inefficiency of vasoconstrictors, plasma substituting drugs and other symptomatic therapy.
- Allergic reactions (acute severe forms), hemotransfusionic shock, acute anaphylaxis, anaphylactoid reactions.
- Wet brain (including against the background of a tumor of a brain or connected with surgical intervention, radiation therapy or an injury of the head).
- Bronchial asthma (severe form), asthmatic status.
- General diseases of connecting fabric (system lupus erythematosus, pseudorheumatism).
- Acute adrenal insufficiency.
- Thyrocardiac crisis.
- Acute hepatitis, hepatic coma.
- Reduction of the inflammatory phenomena and the prevention of Cicatricial narrowings (at poisoning with the cauterizing liquids).

Route of administration and doses:

The dose of drug and duration of treatment is established by the doctor individually depending on indications and disease severity. Tablets. All daily dose of drug is recommended to be accepted inside once or a double daily dose - every other day taking into account a circadian rhythm of endogenous secretion of glucocorticosteroids in the range from 6 to 8 o'clock in the morning. The high daily dose can be distributed on 2-4 receptions, at the same time in the mornings it is necessary to accept a high dose. A pill should be taken in time or directly after food, washing down with a small amount of liquid.

The initial dose of drug can make from 4 mg to 48 mg of Methylprednisolonum a day, depending on the nature of a disease. At less serious illness use of lower doses is usually enough though also higher doses can be required by certain patients. High doses can be required at such diseases and states as multiple sclerosis (200 mg/days), wet brain (200-1000 mg/days) and organ transplantation (to 7 mg/kg/days). If through a sufficient span the satisfactory clinical effect is not gained, drug the patient should cancel and appoint other type of therapy.

To children the dose is defined by the doctor taking into account the weight or a body surface. At adrenal insufficiency - in 0,18 mg/kg or 3,33 mg / кв.м in days in 3 receptions, at other indications - on 0,42-1,67 mg/kg or 12,5-50 mg / кв.м in days in 3 receptions.

At long administration of drug the daily dose should be reduced gradually.

Long therapy cannot be stopped suddenly!

Parenterally the drug is administered in the form of slow intravenous jet injections or intravenous infusions, and also intramuscular injections.

Solution preparation. Solution for injections prepares by addition of solvent in a bottle with lyophilisate just before use. The prepared solution contains 62,5 mg/ml of Methylprednisolonum.

As additional therapy at life-threatening states enter 30 mg/kg of body weight in/in within not less than 30 min. It is possible to repeat introduction of this dose each 4-6 hour within no more 48th hour.

Pulse therapy at treatment of diseases at which GKS-therapy is effective, at exacerbations of a disease and/or at inefficiency of standard therapy.

The recommended schemes of therapy:
Rheumatic diseases: 1 g/days in/in within 1 - 4 days or 1 g/month in/in within 6 months
System lupus erythematosus: 1 g/days in/in within 3 days
Multiple sclerosis: 1 g/days in/in within 3 or 5 days
Edematous states, for example, glomerulonephritis, lupoid nephrite: 30 mg/kg in/in every other day within 4 days or 1 g/days within 3, 5 or 7 days

The doses stated above should be entered within not less than 30 min., introduction can be repeated if within a week it after performing treatment was not reached improvement or if it is demanded by a condition of the patient. Oncological diseases in an end-stage - for improvement of quality of life: enter 125 mg/days in/in daily during up to 8 weeks.

Prevention of nausea and vomiting, connected with chemotherapy concerning oncological diseases. At the chemotherapy which is characterized by insignificant or srednevyrazhenny emetic action enter 250 mg in/in within not less than 5 min. in 1 hour prior to administration of chemotherapeutic drug, at the beginning of chemotherapy, and also after its termination. At the chemotherapy which is characterized by the expressed emetic action enter 250 mg in/in within not less than 5 min. in combination with the corresponding doses of Metoclopramidum or phenyl propyl ketone in 1 hour prior to administration of chemotherapeutic drug, then on 250 mg in/in at the beginning of chemotherapy and after its termination.

At other indications the initial dose makes 10-500 mg in/in depending on the nature of a disease. For a short course at serious acute conditions higher doses can be required. The initial dose which is not exceeding 250 mg should be entered in/in within not less than 5 min., doses enter over 250 mg within not less than 30 min. The subsequent doses enter in/in or in oil, at the same time duration of intervals between introductions depends on reaction of the patient to therapy and on his clinical state.

Children should enter lower doses (but not less than 0,5 mg/kg/days), however at the choice of a dose first of all consider weight of a state and reaction of the patient to therapy, but not age and body weight.

Features of use:

It is necessary to store the prepared solution for parenteral administration at the room temperature (15 °C-20 of °C) and to use within 12 hours. If the prepared solution is stored in the refrigerator at a temperature of 2 ° -8 °C, then it can be used within 24 hours. During treatment by Methypredum (especially long) observation of the oculist, control of arterial pressure, a condition of water and electrolytic balance, and also a picture of peripheral blood and concentration of glucose in blood is necessary.

For the purpose of reduction of by-effects it is possible to appoint antacids, and also to increase intake of potassium in an organism (a diet, potassium drugs). Food has to be protein-rich, vitamins, with restriction of content of fats, carbohydrates and table salt.

Effect of drug amplifies at patients with a hypothyroidism and cirrhosis. Drug can increase the existing emotional instability or psychotic disturbances. At the instruction to psychoses in the anamnesis Methypredum in high doses is appointed under strict control of the doctor.

With care it is necessary to apply at an acute and subacute myocardial infarction - distribution of the center of a necrosis, delay of formation of cicatricial fabric and a rupture of a cardiac muscle is possible.

In stressful situations during the supporting treatment (for example, surgeries, an injury or infectious diseases) it is necessary to carry out dose adjustment of drug in connection with increase in need for glucocorticosteroids.

At sudden cancellation, especially in case of the previous use of high doses, development of a syndrome of "cancellation" (anorexia, nausea, block, generalized musculoskeletal pains, the general weakness), and also an exacerbation of a disease concerning which Methypredum was appointed is possible.

During treatment it is not necessary to carry out by Methypredum vaccination in connection with decrease in its efficiency (immune response).

Appointing Methypredum at intercurrent infections, septic states and tuberculosis, it is necessary to carry out treatment by antibiotics of bactericidal action at the same time.

At children during prolonged treatment by Methypredum careful observation of dynamics of growth and development is necessary. To children who during treatment were in contact with patients with measles or chicken pox preventively appoint specific immunoglobulins. Owing to weak mineralokortikoidny effect for replacement therapy at adrenal insufficiency Methypredum is used in a combination from mineralokortikoida.

At patients with a diabetes mellitus it is necessary to control concentration of glucose in blood and if necessary to adjust a dose of hypoglycemic means.

Radiological control of bone and joint system (pictures of a backbone, brush) is shown.

Methypredum with latent infectious diseases of kidneys and urinary tract is capable to cause a leukocyturia in patients that can have diagnostic value. Methypredum increases the maintenance of metabolites of 11-and 17 oxyketocorticosteroids.

Side effects:

Frequency of development and expressiveness of side effects depends on duration of use, size of the used dose and a possibility of observance of a circadian rhythm of purpose of Methypredum. At use of Methypredum can be noted:

From endocrine system: decrease in tolerance to glucose, a steroid diabetes mellitus or manifestation of a latent diabetes mellitus, oppression of function of adrenal glands, an Icenco-Cushing syndrome (a crescent-shaped face, obesity of pituitary type, a hirsutism, increase in arterial pressure, a dysmenorrhea, an amenorrhea, muscular weakness, striya), a delay of sexual development at children.

From the alimentary system: nausea, vomiting, pancreatitis, steroid stomach ulcer and duodenum, erosive esophagitis, gastrointestinal bleedings and perforation of a wall of digestive tract, increase or loss of appetite, digestion disturbance, meteorism, hiccups. In rare instances - increase in activity of "hepatic" transaminases and an alkaline phosphatase. From cardiovascular system: arrhythmias, bradycardia (up to a cardiac standstill); development (at predisposed patients) or strengthening of expressiveness of heart failure, change on the electrocardiogram, characteristic of a hypopotassemia, increase in arterial pressure, hypercoagulation, fibrinferments. Patients with an acute and subacute myocardial infarction have a distribution of the center of a necrosis, delay of formation of cicatricial fabric that can lead to a rupture of a cardiac muscle.

From a nervous system: delirium, disorientation, euphoria, hallucinations, maniac-depressive psychosis, depression, paranoia, increase in intracranial pressure, nervousness or concern, sleeplessness, dizziness, вертиго, cerebellum pseudoneoplasm, headache, spasms.

From sense bodys: a back subkapsulyarny cataract, increase in intraocular pressure with possible injury of an optic nerve, tendency to development of consecutive bacterial, fungal or viral infections of eyes, trophic changes of a cornea, an exophthalmos, sudden loss of sight (at parenteral administration in the head, a neck, nasal sinks, head skin adjournment of crystals of drug in eye vessels is possible).

From a metabolism: the increased calcium removal, a hypocalcemia, increase in body weight, negative nitrogenous balance (the increased disintegration of proteins), the increased perspiration.
Caused by mineralokortikoidny activity - a delay of liquid and sodium (peripheral hypostases), a hypernatremia, a gipokaliyemichesky syndrome (a hypopotassemia, arrhythmia, a mialgiya or a spasm of muscles, unusual weakness and fatigue).
 
From a musculoskeletal system: delay of growth and processes of ossification at children (premature closing of epiphyseal regions of growth), osteoporosis (it is very rare - pathological fractures of bones, an aseptic necrosis of a head humeral and a femur), a rupture of sinews of muscles, a steroid myopathy, decrease in muscle bulk (atrophy).

From integuments and mucous membranes: the slowed-down healing of wounds, petechias, ecchymomas, thinning of skin, hyper - or hypopigmentation, steroid eels, striya, tendency to development of a pyoderma and candidiases. Allergic reactions: skin rash, itch, acute anaphylaxis, local allergic reactions.

Local at parenteral administration: burning, numbness, pain, a pricking in an injection site, an infection in an injection site, is rare - a necrosis of surrounding fabrics, formation of hems in the place of an injection; an atrophy of skin and hypodermic cellulose at intramuscular introduction (introduction to a deltoid muscle is especially dangerous).

Others: development or an exacerbation of infections (emergence of this side effect is promoted jointly by the applied immunodepressants and vaccination), a leukocyturia, a syndrome of "cancellation", "inflows" of blood to the head.

Interaction with other medicines:

Pharmaceutical incompatibility of Methylprednisolonum with other intravenously administered drugs is possible - it is recommended to be entered separately from other drugs (intravenously bolyusno, or through other dropper as the second solution).

Co-administration of Methylprednisolonum with:
inductors of "hepatic" microsomal enzymes (phenobarbital, rifampicin, Phenytoinum, theophylline, ephedrine) leads to decrease in its concentration (increase in speed of metabolism);
diuretics (especially "thiazide" and inhibitors of a karboangidraza) and Amphotericinum In - can lead to strengthening of removal from an organism of potassium and increase in risk of development of heart failure; inhibitors of a karboangidraza and "loopback" diuretics can increase risk of development of osteoporosis;
with natriysoderzhashchy drugs - to development of hypostases and increase in arterial pressure;
cardiac glycosides - their portability worsens and the probability of development of a ventricular ekstrasitoliya increases (because of the caused hypopotassemia);
indirect anticoagulants - weakens (strengthens) their action less often (it is required to dose adjustment); anticoagulants and trombolitika - the risk of development of bleedings from ulcers in digestive tract increases;
ethanol and non-steroidal anti-inflammatory drugs (NPVP) - the risk of emergence of erosive cankers in digestive tract and development of bleedings (in a combination with NPVP at treatment of arthritises the dose decline of glucocorticosteroids because of summation of therapeutic effect is possible) amplifies;
indometacin - the risk of development of side effects of Methylprednisolonum increases (replacement by Methylprednisolonum indometacin from communication with albumine);
paracetamol - the risk of development of a hepatotoxic (induction of liver enzymes and formation of a toxic metabolite of paracetamol) increases;
acetylsalicylic acid - accelerates its removal and reduces concentration in blood (at cancellation of Methylprednisolonum the level of salicylates in blood increases and the risk of development of by-effects increases);
insulin and peroral hypoglycemic drugs, antihypertensives - their efficiency decreases; vitamin D - its influence on absorption of calcium in intestines decreases;
somatotropic hormone - reduces efficiency of the last, and with prazikvantely - its concentration;
M-holinoblokatorami (including antihistaminic drugs and tricyclic antidepressants) and nitrates - promotes increase in intraocular pressure;
isoniazid and meksiletiny - increases their metabolism (especially at "slow" atsetilator) that leads to decrease in their plasma concentration.

AKTG strengthens action of Methylprednisolonum.

Ergocalciferol and parathormone interfere with development of the osteopathy caused by Methylprednisolonum.

Cyclosporine and кетоконазол, slowing down metabolism of Methylprednisolonum, can increase its toxicity in some cases.

Co-administration of androgens and steroid anabolic drugs with Methylprednisolonum promotes development of peripheral hypostases and a hirsutism, appearance of eels.

Are oestrogenic and oral estrogensoderzhashchy contraceptives reduce clearance of Methylprednisolonum that can be followed by strengthening of expressiveness of its action.

Mitotanum and other inhibitors of function of bark of adrenal glands can cause need of increase in a dose of Methylprednisolonum.

At simultaneous use with live antiviral vaccines and against the background of other types of immunizations increases risk of activation of viruses and development of infections.

Immunodepressants increase risk of development of infections and a lymphoma or other limfoproliferativny disturbances connected with Epstein-Burra's virus.

Antipsychotic means (neuroleptics) and Azathioprinum increase risk of development of a cataract at purpose of Methylprednisolonum. Co-administration of antacids reduces absorption of Methylprednisolonum.

At simultaneous use with anti-thyroid drugs decreases, and with thyroid hormones - the clearance of Methylprednisolonum increases.

Contraindications:

For short-term use according to vital indications the only contraindication is hypersensitivity to Methylprednisolonum or components of drug.

At children in a growth period of GKS have to be applied only according to absolute indications and under especially careful observation of the attending physician.

With care it is necessary to appoint drug at the following diseases and states:
digestive tract diseases - a peptic ulcer of a stomach and duodenum, an esophagitis, gastritis, an acute or latent round ulcer, recently created intestines anastomosis, nonspecific ulcer colitis with threat of perforation or abscessing, a diverticulitis;
parasitic and infectious diseases of the virus, fungal or bacterial nature (now or recently postponed, including recent contact by the patient) - the herpes simplex surrounding herpes (a viremichesky phase), chicken pox, measles; amebiasis, strongyloidosis; system mycosis; active and latent tuberculosis. Use at serious infectious diseases is admissible only against the background of specific therapy;
pre-and the postvaccinal period (8 weeks to and 2 weeks after vaccination), lymphadenitis after BTsZh inoculation;
immunodeficiency (including AIDS or HIV infection);
diseases of cardiovascular system (including recently postponed myocardial infarction - at patients with an acute and subacute myocardial infarction distribution of the center of a necrosis, delay of formation of cicatricial fabric and, thereof, - a rupture of a cardiac muscle), heavy chronic heart failure, arterial hypertension, a lipidemia is possible);
endocrine diseases - a diabetes mellitus (including disturbance of tolerance to carbohydrates), a thyrotoxicosis, a hypothyroidism, Itsenko-Cushing's disease, obesity (III IVct.);
heavy chronic renal and/or liver failure, нефроуролитиаз;
the hypoalbuminemia and states contributing to its emergence;
system osteoporosis, gravis myasthenia, acute psychosis, poliomyelitis (except for a form of bulbar encephalitis), open and closed-angle glaucoma;
pregnancy.

Use during pregnancy and breastfeeding

At pregnancy (especially in the I trimester) apply only according to vital indications.

As glucocorticosteroids get into breast milk, in case of need uses of drug during breastfeeding, feeding by a breast is recommended to be stopped.

Overdose:

Strengthening of the by-effects described above is possible. It is necessary to reduce Methypredum dose. Treatment - symptomatic.

Storage conditions:

List B. Tablets on 4 mg or 16 mg. At a temperature from 15 °C to 25 °C.
The lyophilized powder: At a temperature from 15 °C to 25 °C, in the place protected from light. The recovered solution is stored in the refrigerator at a temperature from 2-8 °C within 24 hours. To store in the place, unavailable to children. Period of validity: 5 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 4 mg or 16 mg.

On 30 or 100 tablets in bottles of amber glass with the aluminum screw-on cover providing opening control. On 1 bottle together with the application instruction place in a cardboard pack.

On 30 or 100 tablets in a plastic (polyethylene) bottle, with the screw-on cover providing opening control from the same material. On 1 bottle together with the application instruction place in a cardboard pack.

The lyophilized powder for preparation of solution for intramuscular and intravenous administration of 250 mg in bottles complete with solvent in ampoules on 4 ml. 1 bottle and 1 ampoule together with the application instruction place in a cardboard pack.