Lemod

General characteristics. Structure:

Active agent: sodium Methylprednisolonum succinate of 158.5 mg that corresponds to the maintenance of Methylprednisolonum of 125 mg

Excipients: sodium hydrophosphate anhydrous, sodium phosphate monohydrate monosubstituted.

Solvent: benzyl alcohol (18 mg), water for and (to 2 ml).

Pharmacological properties:

Synthetic GKS. Has immunodepressive, antiinflammatory and antiallergic effect. Interacts with specific cytoplasmatic receptors (receptors for 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: Methylprednisolonum reduces amount of globulins in plasma, induces synthesis of albumine in a liver and kidneys (with increase in coefficient albumine/globulin), inhibits synthesis and strengthens a protein catabolism in muscular tissue.
Lipidic exchange: Methylprednisolonum induces 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: Methylprednisolonum increases absorption of carbohydrates from a GIT, 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: Methylprednisolonum detains sodium and water in an organism, stimulates potassium removal (mineralokortikoidny activity), reduces absorption of calcium from a GIT, reduces a mineralization of a bone tissue.
Antiinflammatory action 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), synthesis of pro-inflammatory cytokines (including interleykin-1, a tumor necrosis factor an alpha), 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 B-cells and interactions of T - and V-lymphocytes, braking of release of cytokines (interleykina-1, 2; interferon scale) from lymphocytes and macrophages and decrease in antibody formation.
Antiallergic action 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 and other biologically active agents, reduction of number of the circulating basophiles, suppression of development of adenoid and connecting tissue, reduction of number of T - and V-lymphocytes, mast cells, 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 β-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 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. Absorption. At intake it is quickly soaked up, absorption makes more than 70%. Is exposed to effect of "the first passing" through a liver. At introduction in oil absorption - full and rather bystry. Absorption at introduction to hip muscles more bystry, than at introduction to gluteuses. Bioavailability at introduction in oil - 89%.

Distribution. Cmax after intake is reached in 1.5 h, at introduction in oil in 0.5-1 h.

Cmax in a blood plasma in/in introductions in a dose of 30 mg/kg is reached later within 20 min. or in/in drop introduction in a dose of 1 g within 30-60 min. - and reaches 20 mkg/ml.
Cmax in a blood plasma after introduction of 40 mg in oil is reached approximately in 2 h - and makes 34 mkg/ml.
Linkng with proteins of plasma (only with albumine) - 62% irrespective of the entered dose.
Gets through GEB and a placental barrier.

Metabolism. It is metabolized preferential in a liver.

Removal. Metabolites (11-keto-and 20 oxycompounds) have no hormonal activity and are removed preferential by kidneys (about 85% of the entered dose are found during 24 h in urine and about 10% - in Calais). T1/2 makes 3-4 h. Metabolites are found in breast milk.
At a chronic renal failure removal does not change.

Indications to use:

— endocrine diseases: primary and secondary adrenal insufficiency (in need of a combination to mineralokortikoida, especially in pediatric practice); acute adrenal insufficiency (there can be a need for addition of mineralokortikoid); the shock which is a consequence of adrenal insufficiency or shock which does not give in to therapy by standard methods when existence of adrenal insufficiency is possible (if mineralokortikoidny action is undesirable); in the preoperative period, in case of a severe injury or a serious illness at patients with the established or suspected adrenal insufficiency; inborn adrenal struma; subacute thyroiditis; a hypercalcemia against the background of an oncological disease;
— allergic diseases and states: bronchial asthma, asthmatic state, Quincke's disease, acute anaphylaxis, serum disease, atopic dermatitis;
— musculoskeletal system diseases (including rheumatic): posttraumatic osteoarthritis, bursitis, tendovaginitis, epicondylitis, fibrositis, psoriasis arthritis and gout, ankylosing spondylitis;
— general diseases of connecting fabric: system lupus erythematosus (and lupoid nephrite), acute rheumatic carditis, system dermatomyositis, pseudorheumatism, juvenile pseudorheumatism;
— skin diseases: heavy mnogoformny erythema (Stephens-Johnson's syndrome), pempigus, exfoliative dermatitis, herpetiform violent dermatitis, fungoid mycosis, severe forms of psoriasis and seborrheal dermatitis;
— gastrointestinal diseases: ulcer colitis, disease Krone;
— diseases of a respiratory organs: the fulminant and disseminated tuberculosis (in combination with the corresponding antitubercular therapy), a symptomatic sarcoidosis, diffusion intersticial fibrosis, an aspiration pneumonitis, a berylliosis, Leffler's syndrome which is not giving in to therapy by other means;
— diseases of a nervous system: multiple sclerosis (in the period of an aggravation), the brain hypostasis caused by a tumor - primary or metastatic, and/or connected with surgical or radiation therapy;
— eye diseases: eye Herpes zoster form, iritis and iridocyclitis, chorioretinitis, diffusion back uveitis and choroiditis, optic neuritis, sympathetic ophthalmia, inflammation of a front segment, allergic conjunctivitis, allergic regional helcomas, keratitis;
— oncological diseases and states: lymphoma and leukemias (as a part of complex therapy), prevention of nausea and vomiting, connected with chemotherapy;
— hematologic diseases: the acquired (autoimmune) hemolitic anemia, an idiopathic Werlhof's disease at adults (only in/in introduction; introduction in oil is contraindicated), secondary thrombocytopenia at adults, an eritroblastopeniya (erythrocyte anemia), inborn (erythroidal) hypoplastic anemia;
— edematous syndrome: for stimulation of a diuresis and achievement of remission of a proteinuria at patients with a nephrotic syndrome without uraemia;
— other diseases and states: reactions of graft rejection.

Route of administration and doses:

Lemod it is possible to enter in a look in/in or injections in oil or in a look into infusions. At medical emergencies it is preferable to begin treatment with in/in an injection.
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.
As additional therapy at life-threatening states: 30 mg/kg of body weight in/in within not less than 30 min. Introduction of this dose can be repeated each 4-6 h during no more than 48 h.
The recommended schemes pulse therapy at treatment of diseases at which therapy of GKS is effective at exacerbations of diseases and/or are presented to inefficiency of standard therapy in the table.

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 (glomerulonephritis, lupoid nephrite)	30 mg/kg in/in every other day within 4 days or 1 g / in/in 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 it is demanded by a condition of the patient.
Oncological diseases in an end-stage
For improvement of quality of life - on 125 mg/days in/in daily lasting 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.
For strengthening of effect with the first dose of drug Lemod it is possible to administer the drugs of a hlorfenotiazin.
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.

Features of use:

During treatment by drug Lemod (especially long) observation of the oculist, control of the ABP, a condition of water and electrolytic balance, and also a picture of peripheral blood and level of glucose of 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 in the anamnesis Lemod in high doses appoint to psychoses under strict control of the doctor.

At the wet brain caused by a head injury, drug cannot be used in connection with increase in mortality.

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 GKS.

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

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

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

Owing to weak mineralokortikoidny effect for replacement therapy at adrenal insufficiency Lemod use in a combination from mineralokortikoida.

At patients with a diabetes mellitus it is necessary to control the content of glucose of blood and if necessary to korrigirovat therapy.

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

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

Drug in the form of lyophilisate for in/in and introductions in oil should be applied to preparation of solution only in the conditions of a hospital.

Use in pediatrics

At children during prolonged treatment by drug Lemod 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.

Drug for parenteral administration contains benzyl alcohol in a dosage form. It is established that benzyl alcohol can cause a suffocation syndrome with a lethal outcome in premature newborns. Drug is not recommended to be used at newborns.

Side effects:

Frequency of development and expressiveness of side effects depend on duration of use, size of the used dose and a possibility of observance of a circadian rhythm of appointment.

From endocrine system: decrease in tolerance to glucose, a steroid diabetes mellitus or manifestation of a latent diabetes mellitus, eels, oppression of function of adrenal glands, an Icenco-Cushing syndrome (a crescent-shaped face, obesity of pituitary type, a hirsutism, increase in the ABP, 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, bleedings and perforation of a GIT, increase or loss of appetite, digestion disturbance, meteorism, hiccups; seldom - increase in activity of hepatic transaminases and ShchF.

From cardiovascular system: arrhythmias, bradycardia, a cardiac standstill, aggravation of the phenomena or development of heart failure (at predisposed patients), on the ECG of change characteristic of a hypopotassemia, increase in the ABP, hypercoagulation, fibrinferments, at patients with an acute and subacute myocardial infarction is possible distribution of the center of a necrosis, delay of formation of cicatricial fabric that can lead to a rupture of a cardiac muscle.

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

From sense bodys: 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), 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.

From a metabolism: a delay of liquid and sodium (hypostases), a hypernatremia, a gipokaliyemichesky syndrome (a hypopotassemia, arrhythmia, a mialgiya or a spasm of muscles, unusual weakness), the increased calcium removal, a hypocalcemia, increase in body weight, negative nitrogenous balance (the increased disintegration of proteins), the increased sweating.

Allergic reactions: generalized (skin rash, itch, acute anaphylaxis) allergic reactions, local allergic reactions.

Others: an exacerbation of infections, increase in activity system renin-angiotensin-aldosteronovoy, a leukocyturia, a withdrawal, rushes of blood to the person.

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

Interaction with other medicines:

Co-administration of Methylprednisolonum

- with inductors of microsomal enzymes of a liver (phenobarbital, Phenytoinum, theophylline, rifampicin, ephedrine) leads to decrease in its concentration in a blood plasma;

- with diuretics (especially tiazidopodobny, "loopback" and inhibitors of a karboangidraza) and Amphotericinum In leads to strengthening of removal from an organism of K+ and increase in risk of development of heart failure, and also increase in risk of development of osteoporosis;

- at long therapy Lemod increases the content of folic acid;

- with natriysoderzhashchy drugs leads to development of hypostases and increase in the ABP;

- with cardiac glycosides leads to deterioration in their portability and increase in probability of development of a ventricular ekstrasitoliya (because of the caused hypopotassemia);

- with indirect anticoagulants leads to easing (more rare to strengthening) their actions (dose adjustment is required);

- with anticoagulants and trombolitika leads to increase in risk of development of bleedings from GIT ulcers;

- with ethanol and NPVS leads to strengthening of risk of emergence of erosive cankers of a GIT and development of bleedings (in a combination with NPVS at treatment of arthritises GKS dose decline because of summation of therapeutic effect can be required);

- with paracetamol leads to increase of risk of development of a hepatotoxic (induction of liver enzymes and formation of a toxic metabolite of paracetamol);

- with acetylsalicylic acid leads to acceleration of removal and decrease in concentration in a blood plasma of the last (at cancellation of Methylprednisolonum the level of salicylates in blood increases and the risk of development of by-effects increases);

- with insulin and peroral hypoglycemic drugs, antihypertensives leads to reduction of their efficiency;

- with vitamin D leads to decrease in influence of the last on absorption of Sa2 + in intestines;

- with somatotropic hormone leads to decrease in efficiency of the last, and with prazikvantely - to decrease in its concentration in a blood plasma;

- with m-holinoblokatorami, funds from m-holinoblokiruyushchey activity (including antihistaminic drugs and tricyclic antidepressants) and nitrates leads to increase in intraocular pressure;

- with an isoniazid and meksiletiny leads to increase in their metabolism (especially at bystry acetylizers) owing to what their plasma concentration decrease.

Indometacin, forcing out Methylprednisolonum from communication with albumine, increases risk of development of its side effects.

AKTG strengthens action of Methylprednisolonum.

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

Ketokonazol, slowing down metabolism of Methylprednisolonum, can increase its toxicity in some cases.

Combined use with cyclosporine causes mutual oppression of metabolism, increasing risk of development of side effects of both drugs (at combined use cases of developing of spasms were noted).

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 immunization the risk of activation of viruses and development of infections increases.

Tricyclic antidepressants can increase expressiveness of the depression caused by reception of GKS (are not shown for therapy of these side effects).

Antipsychotic means (neuroleptics) and Azathioprinum increase risk of development of a cataract at purpose of Methylprednisolonum.

The hypopotassemia caused by GKS can increase expressiveness and duration of muscular blockade against the background of use of muscle relaxants.

Co-administration of antacids reduces absorption of Methylprednisolonum.

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

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

Pharmaceutical interaction

Methylprednisolonum pharmaceutical is incompatible with other medicines (can form insoluble compounds).

Contraindications:

— cornea herpes;
— acute round ulcer;
— acute psychoses;
— active tuberculosis;
— heavy diabetes mellitus;
— system fungal infections.
For short-term use according to vital indications the only contraindication is hypersensitivity to drug.

With care it is necessary to appoint drug at:
— gastrointestinal diseases - a peptic ulcer of a stomach and a duodenum, an esophagitis, gastritis, an acute or latent round ulcer, recently created anastomosis of intestines, NYaK with threat of perforation or abscessing, a diverticulitis;
— the parasitic and infectious diseases of the virus, fungal or bacterial nature (proceeding now or which are recently postponed including recent contact with the patient) - the herpes simplex surrounding herpes (a viremichesky phase), chicken pox, measles, an amebiasis, a 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 - 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 a rupture of a cardiac muscle is possible), heavy chronic heart failure, arterial hypertension, a lipidemia;
— endocrine diseases - a diabetes mellitus (including disturbance of tolerance to carbohydrates), a thyrotoxicosis, a hypothyroidism, Itsenko-Cushing's disease, obesity (the III-IV degree);
— to a heavy chronic renal failure, nefrourolitiaza;
— heavy chronic liver failure;
— the hypoalbuminemia and states contributing to its emergence;
— system osteoporosis, a myasthenia, acute psychosis, poliomyelitis (except for a form of bulbar encephalitis), open and closed-angle glaucoma;
— pregnancies.

At children in a growth period drug should be used only according to absolute indications and under especially careful observation of the attending physician.
Use of the drug LEMOD® at pregnancy and feeding by a breast

At pregnancy (especially in the I trimester) use of drug is possible only according to vital indications when the estimated advantage for mother surpasses potential risk for a fruit.
In need of use of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Use at abnormal liver functions
With care to apply at a heavy chronic liver failure.

Use at renal failures
With care to apply at a heavy chronic renal failure, a nefrourolitiaza.

Overdose:

Symptoms: strengthening of by-effects is possible.
Treatment: it is necessary to reduce a drug dose, to appoint a symptomatic treatment.

Storage conditions:

Drug should be stored in the unavailable to children, dry, protected from light place at a temperature from 15 °C to 25 °C.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for пригот. solution for in/in and introductions of 125 mg in oil: фл. in set. with solvent.