Lemod - instructions for use, doses, side effects, contraindications

Synthetic glucocorticosteroid (GCS). Has anti-inflammatory, anti-allergic and immunosuppressive effects. Interacts with specific cytoplasmic receptors (receptors for glucocorticosteroids (GCS) are present in all tissues, especially in the liver), with the formation of a complex inducing the formation of proteins (including enzymes that regulate vital processes in cells.)

Protein metabolism: reduces the number of globulins in the plasma, increases the synthesis of albumins in the liver and kidneys (with increasing albumin / globulin ratio), reduces synthesis and enhances protein catabolism in muscle tissue.

Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (accumulation of fat occurs mainly in the area of the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.

Carbohydrate metabolism: increases the absorption of carbohydrates fromgastrointestinal tract; increases the activity of glucose-6-phosphatase (increased intake of glucose from the liver into the blood); increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases (activation of gluconeogenesis); promotes the development of hyperglycemia.

Water-electrolyte exchange: delays sodium (Na +) and water in the body, stimulates the excretion of potassium (K +) (mineralocorticoid activity), reduces the absorption of calcium (Ca²⁺) from the gastrointestinal tract, reduces the mineralization of bone tissue.

The anti-inflammatory effect is associated with the suppression of the release of eosinophils and mast cells by inflammatory mediators; inducing the formation of lipocortins and reducing the number of mast cells that produce hyaluronic acid; with a decrease in the permeability of capillaries; stabilization of cell membranes (especially lysosomal) and membranes of organelles. It acts on all stages of the inflammatory process: it inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin depresses phospholipase A2, suppresses the liberation of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes that promote inflammation,allergies, etc.), the synthesis of "pro-inflammatory cytokines" (interleukin 1, tumor necrosis factor alpha, etc.); increases the resistance of the cell membrane to the action of various damaging factors.

Immunosuppressive effect is caused by induced lymphoid tissue involution, suppression of lymphocyte proliferation (especially T-lymphocytes), suppression of B-cell migration and interaction of T and B lymphocytes, inhibition of release of cytokines (interleukin-1, 2, gamma-interferon) from lymphocytes and macrophages and a decrease in the formation of antibodies.

The antiallergic effect develops as a result of a decrease in the synthesis and secretion of mediators of allergy, inhibition of release from sensitized mast cells and basophils of histamine and other biologically active substances, a decrease in the number of circulating basophils, suppression of lymphoid and connective tissue development, a decrease in the number of T- and B-lymphocytes, cells, reducing the sensitivity of effector cells to mediators of allergy, inhibition of antibody formation, changes in the immune response of the body.

In obstructive airway disease,inhibition of inflammatory processes, prevention or reduction of the degree of edema of the mucous membranes, a decrease in the eosinophilic infiltration of the submucosal layer of bronchial epithelium and the deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucosa.

Increases the sensitivity of beta-adrenergic receptors of small and medium-sized bronchial tubes to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by reducing its production.

Suppresses the synthesis and secretion of ACTH and, again, the synthesis of endogenous GCS.

It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

Pharmacokinetics:

When ingested quickly absorbed, the absorption is more than 70%. Has the effect of "first pass" through the liver.

With the / m introduction, the absorption is complete and fairly rapid. Absorption when injected into the muscles of the thigh is faster than when injected into the gluteal muscles. Bioavailability in the / m introduction - 89%.

Linkage to plasma proteins is 62% (binds only to albumin), regardless of the dose administered.Time to reach the maximum concentration after ingestion -1.5 hours, with the / m introduction - 0.5-1 h. Maximum concentration (FROM_max) in plasma after intravenous administration at a dose of 30 mg / kg for 20 minutes or iv drip in a dose of 1 g for 30-60 minutes reaches 20 μg / ml. After a / m introduction of 40 mg after about 2 h, C_max in the plasma, which is 34 μg / ml.

Penetrates through the hemoencephalic and placental barrier. Metabolites are found in breast milk.

Metabolized mainly in the liver, metabolites (11-keto- and 20-hydroxy compounds) do not have hormonal activity and are excreted mainly by the kidneys (about 85% of the administered dose is detected within 24 hours in urine and about 10% in feces). The half-life is 3-4 hours.

With chronic renal failure, excretion does not change.

Indications:

The solution for intravenous and intramuscular administration is used for the treatment of diseases:

Endocrine diseases

Primary and secondary adrenal insufficiency (if necessary in combination with mineralocorticoids, especially in pediatric practice); acute adrenal insufficiency (it may be necessary to add mineralocorticoids); shock, which is a consequence of adrenal insufficiency,or shock, which can not be treated by standard methods, when adrenal insufficiency is possible (if mineralocorticoid action is undesirable); in the preoperative period, in the case of severe trauma or severe illness in patients with established or suspected adrenal insufficiency; congenital adrenal hyperplasia; subacute thyroiditis; Hypercalcemia on the background of an oncological disease.

Allergic diseases and conditions

Bronchial asthma, asthmatic condition, angioedema, anaphylactic shock, serum sickness, atopic dermatitis.

Rheumatic diseases

Post-traumatic osteoarthritis, bursitis, tendovaginitis, epicondylitis, fibrositis, psoriatic arthritis and gout, ankylosing spondylitis.

Systemic connective tissue diseases

Systemic lupus erythematosus (and lupus nephritis), acute rheumatic carditis, systemic dermatomyositis, rheumatoid arthritis, juvenile rheumatoid arthritis.

Skin diseases

Severe multiform erythema (Stevens-Johnson syndrome), pemphigus, exfoliative dermatitis, herpetiform bullous dermatitis, mushroom mycosis,severe forms of psoriasis and seborrheic dermatitis.

Diseases of the gastrointestinal tract

Ulcerative colitis, Crohn's disease.

Diseases of the respiratory tract

Lightning and disseminated tuberculosis (in combination with appropriate anti-tuberculosis therapy), symptomatic sarcoidosis, diffuse interstitial fibrosis, aspiration pneumonitis, berylliosis, Leffler's syndrome, not amenable to therapy by other means.

Diseases of the nervous system

Multiple sclerosis (during an exacerbation).

Eye diseases

Eye shape Herpes zoster, iritis and iridocyclitis, chorioretinitis, diffuse posterior uveitis and choroiditis, optic neuritis, sympathetic ophthalmia, anterior segment inflammation, allergic conjunctivitis, allergic marginal ulcers of the cornea, keratitis.

Oncological diseases

Lymphoma and leukemia (as part of complex therapy).

Hematological diseases

Acquired (autoimmune) hemolytic anemia, idiopathic thrombocytopenic purpura in adults (only intravenously, intramuscularly contraindicated), secondary thrombocytopenia in adults, erythroblastoma (erythrocyte anemia), congenital (erythroid) hypoplastic anemia.

Edema Syndrome

To stimulate diuresis and achieve remission of proteinuria in patients with nephrotic syndrome without uremia.

Nervous system

Cerebral edema caused by a tumor - primary or metastatic, and / or associated with surgical or radiotherapy, multiple sclerosis.

Organ transplantation

Rejection reactions of the graft.

Other

Prevention of nausea and vomiting associated with chemotherapy for cancer.

Contraindications:

For short-term use according to "vital" indications, the only contraindication is hypersensitivity.

Absolute contraindications to prolonged use are: corneal herpes, acute peptic ulcer, acute psychosis, active tuberculosis, severe diabetes mellitus, systemic fungal infections.

The drug in a dosage form for parenteral administration contains a gasoline alcohol. It is established that gasoline alcohol can cause a "suffocation syndrome" with a fatal outcome in premature newborns. The drug is not recommended for use in newborns.

Carefully:

With caution, the drug should be administered in the following conditions and conditions:

- Diseases of the gastrointestinal tract: peptic ulcer of stomach and duodenum, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with perforation or abscessing, diverticulitis;

- Parasitic and infectious diseases of a viral, fungal or bacterial nature (current or recent, including recent contact with a patient): herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amebiasis, strongyloidiasis; systemic mycosis; active and latent tuberculosis. The use in severe infectious diseases is permissible only against the background of specific therapy;

- Pre- and post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination;

- Immunodeficiency conditions (including AIDS or HIV infection);

- Diseases of the cardiovascular system, incl. recent myocardial infarction (in patients with acute and subacute myocardial infarction, the spread of the necrosis foci, slowing the formation of scar tissue and, as a result, the rupture of the heart muscle), severe chronic heart failure, hypertension, hyperlipidemia;

- Endocrine diseases: diabetes mellitus (including a violation of carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease, obesity (III-IV c);

- Severe chronic renal and / or hepatic insufficiency, nephrourolythiasis;

- Hypoalbuminemia and conditions predisposing to its occurrence;

- Systemic osteoporosis, myasthenia gravis gravis, acute psychosis, poliomyelitis (except for the form of bulbar encephalitis), open and closed angle glaucoma;

- Pregnancy;

- In children during the growth period the drug should be used only under absolute indications and under the special supervision of the attending physician.

Pregnancy and lactation:

When pregnancy (especially in the first trimester) is used for life indications.

As glucocorticosteroids pass into breast milk, if breastfeeding is necessary during breastfeeding, breast-feeding should be discontinued.

Dosing and Administration:

Lemodus can be administered as an intravenous or intravenous injection or as an intravenous infusion, but for urgent conditions it is advisable to start treatment with iv injection.

Children lower doses should be administered (but not less than 0.5 mg / kg / day), however, when choosing a dose, first of all, the severity of the condition and the response of the patient to therapy,but not age and body weight.

As an additional therapy for life-threatening conditions: 30 mg / kg body weight w / w for at least 30 minutes. The administration of this dose can be repeated every 4-6 hours for no more than 48 hours.

Pulse therapy in the treatment of diseases in which glucocorticosteroid therapy is effective, with exacerbations of the disease and / or when standard therapy is ineffective.

Recommended therapy regimens:
Rheumatic diseases:	1 g / day IV for 1 to 4 days or 1 g / month IV in within 6 months
Systemic lupus erythematosus:	1 g / day iv in 3 days
Multiple sclerosis:	1 g / day IV for 3 or 5 days
Osteal conditions, for example, glomerulonephritis, lupus nephritis:	30 mg / kg IV every other day for 4 days or 1 g / day IV for 3, 5 or 7 days

The above doses should be administered for at least 30 minutes and the administration can be repeated if no improvement is achieved within a week after the treatment or if the patient's condition requires it.

Oncological diseases in the terminal stage - to improve the quality of life: 125 mg / day IV daily for up to 8 weeks.

Prevention of nausea and vomiting associated with chemotherapy for cancer

In chemotherapy, characterized by a slight or medium emetic effect, 250 mg IV is administered for at least 5 minutes one hour before the administration of the chemotherapeutic drug, at the beginning of chemotherapy, and after its termination. To intensify the effect with the first dose of Lemod, it is possible to administer chlorphenothiazine preparations.

In chemotherapy characterized by severe emetic action, 250 mg IV is administered for at least 5 minutes in combination with appropriate doses of metoclopramide or butyrophenone one hour before the chemotherapy, then 250 mg IV at the beginning of chemotherapy and after it .

The prepared solution Store in a dark place and use for 2 days.

Side effects:

The frequency of development and severity of side effects depend on the duration of application, the amount of dose used and the possibility of observing the circadian rhythm of the appointment.

From the endocrine system: a decrease in glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, acne, suppression of adrenal function, Itenko-Cushing syndrome (luniform face,obesity of the pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, striae), delayed sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, digestive disorders, flatulence, hiccups. In rare cases - increased activity of "liver" transaminases and alkaline phosphatase.

From the side of the cardiovascular system: arrhythmias, bradycardia, cardiac arrest; aggravation of the phenomena or development of heart failure (in predisposed patients), ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis; in patients with acute and subacute myocardial infarction - the spread of the focus of necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle.

From the nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor, cerebral palsy, headache, convulsions.

From the sense organs: sudden loss of vision (with parenteral administration in the region of the head, neck, nasal concha, scalp may precipitate crystals of the drug in the vessels of the eye), posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, propensity to develop secondary bacterial, fungal or viral eye infections, corneal trophic changes, exophthalmos.

From the side of metabolism: fluid retention and sodium (edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness), increased calcium excretion, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

From the side of the musculoskeletal system: slowing growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rarely pathological bone fractures, aseptic necrosis of bones), steroid myopathy, muscle tendon rupture, muscle mass reduction.

From the skin and mucous membranes: deterioration of wound healing, petechiae, ecchymosis, thinning of the skin, hyper or hypopigmentation, steroid acne, a tendency to develop pyoderma and candidiasis.

Allergic reactions: generalized (skin rash, itching, anaphylactic shock), local allergic reactions.

Local for parenteral administration: burning, numbness, pain, tingling at the injection site, infections at the injection site, rarely - necrosis of surrounding tissues, scar formation at the injection site; atrophy of the skin and subcutaneous tissue with the / m introduction (especially dangerous is the introduction to the deltoid muscle).

Other: exacerbation of infections, increased activity of the renin-angiotensin-aldosterone system, leukocyturia, "withdrawal" syndrome, "flushes" of blood to the face.

Overdose:

It is possible to strengthen the above described side effects. It is necessary to reduce the dose of Lemod.

Treatment simtomatic.

Interaction:

Methylprednisolone pharmaceuticals are incompatible with other drugs (may form insoluble compounds).

Simultaneous administration of methylprednisolone with:

inducers of "hepatic" microsomal enzymes (phenobarbital, phenytoin, theophylline, rifampicin, ephedrine) leads to a decrease in its concentration;
diuretics (especially "thiazide" and inhibitors carbonic anhydrase) and amphotericin B - can lead to increased excretion of K + from the body and an increased risk of developing heart failure;
amphotericin B and carbonic anhydrase inhibitors increase the risk of osteoporosis. Increases (with prolonged therapy) the content of folic acid;
with sodium-containing preparations - to the development of edema and increased blood pressure;
cardiac glycosides - their tolerability worsens and the likelihood of developing ventricular extrasitolia increases (due to induced hypokalemia);
indirect anticoagulants - weakens (less intensifies) their effect (dose adjustment is required);
anticoagulants and thrombolytics - Increased risk of bleeding from ulcers in the gastrointestinal tract;
ethanol and non-steroidal anti-inflammatory drugs (NSAIDs) - the risk of erosive and ulcerative lesions in the gastrointestinal tract and the development of bleeding increases (in combination with NSAIDs, a reduction in the dose of glucocorticosteroids due to the summation of the therapeutic effect is possible in the treatment of arthritis);
paracetamol - The risk of hepatotoxicity increases (induction of hepatic enzymes and the formation of a toxic metabolite of paracetamol);
acetylsalicylic acid - accelerates its excretion and reduces the concentration in the blood (when methylprednisolone is canceled, the level of salicylates in the blood increases and the risk of side effects increases);
insulin and oral hypoglycemic drugs, antihypertensive drugs - their effectiveness is reduced;
vitamin D - its effect on the absorption of Ca decreases²⁺ in the intestine;
somatotropic hormone - reduces the effectiveness of the latter, and with praziquantel - its concentration;
M-holinoblokatorami (including antihistamines and tricyclic antidepressants) and nitrates - promotes increased intraocular pressure;
isoniazid and mexiletine - increases their metabolism (especially in "fast" acetylators), which leads to a decrease in their plasma concentrations.

Inhibitors of carbonic anhydrase and looped diuretics can increase the risk of osteoporosis.

Indomethacin, displacing methylprednisolone from association with albumin, increases the risk of developing its side effects.

ACTH increases the effect of methylprednisolone.

Ergocalciferol and parathyroid hormone interfere with the development of osteopathy caused by methylprednisolone.

Ketoconazole, by slowing the metabolism of methylprednisolone, may in some cases increase its toxicity.

Joint use with cyclosporine causes mutual inhibition of metabolism - the risk of side effects of both drugs (with joint use, cases of seizures were noted).

Simultaneous appointment of androgens and steroid anabolic drugs with methylprednisolone promotes the development of peripheral edema and hirsutism, the appearance of acne.

Estrogens and estrogen-containing oral contraceptives reduce the clearance of methylprednisolone, which may be accompanied by increased severity of his actions.

Mitotane and other inhibitors of adrenal cortex function may necessitate an increase in the dose of methylprednisolone.

With simultaneous use with live antiviral vaccines and against other types of immunizations, increases the risk of virus activation and the development of infections.

Tricyclic antidepressants can increase the severity of depression,(not shown for the therapy of these side effects).

Antipsychotic drugs (antipsychotics) and azathioprine increase the risk of developing cataract in the appointment of methylprednisolone.

Hypokalemia caused by SCS can increase the severity and duration of muscle blockade against the background of muscle relaxants.

Simultaneous administration of antacids reduces the absorption of methylprednisolone.

Immunosuppressants increase the risk of infection and lymphoma or other lymphoproliferative disorders associated with the Epstein-Barr virus.

While the use of antithyroid drugs decreases, and a thyroid hormone - increased clearance of methylprednisolone.

Special instructions:

During treatment with Lemod (especially long-term) it is necessary to observe the oculist, control blood pressure, condition of water-electrolyte balance, as well as pictures of peripheral blood and blood glucose level.

In order to reduce side effects, it is possible to prescribe antacids, and also to increase the intake of potassium in the body (diet, potassium preparations). Food should be rich in proteins, vitamins, with a restriction of fat, carbohydrates and table salt.

The effect of the drug is enhanced in patients with hypothyroidism and liver cirrhosis.

The drug may enhance existing emotional instability or psychotic disorders. When referring to a psychosis in an anamnesis, Lemod in high doses is prescribed under the strict supervision of a doctor.

With edema of the brain, due to head trauma, the drug can not be used due to an increase in mortality.

With caution should be used in acute and subacute myocardial infarction - possibly spreading the focus of necrosis, slowing the formation of scar tissue and rupture of the heart muscle.

In stressful situations during maintenance treatment (for example, surgical operations, trauma or infectious diseases), a correction of the dose of the drug should be made in connection with an increase in the need for glucocorticosteroids.

With the sudden cancellation, particularly in the case of the prior use of high doses may develop the syndrome of "lifting" (anorexia, nausea, lethargy, generalized musculoskeletal pain, fatigue), as well as worsening of the disease, about which he was appointed Lemod.

During treatment with Lemod, the vaccine should not be given due to a decrease in its effectiveness (immune response).

When appointing Lemod in intercurrent infections, septic states and tuberculosis, it is necessary to simultaneously perform antibiotic treatment with bactericidal action.

Children during prolonged treatment with Lemod should carefully monitor the dynamics of growth and development. Children who were in contact with sick measles or chickenpox during the treatment period prophylactically prescribe specific immunoglobulins.

Due to the weak mineralocorticoid effect for replacement therapy for adrenal insufficiency, Lemodus is used in combination with mineralocorticoids.

Patients with diabetes should monitor blood glucose and, if necessary, correct therapy.

An x-ray control of the osteoarticular system (images of the spine, hands) is shown.

Lemod in patients with latent infectious diseases of the kidneys and urinary tract can cause leukocyturia, which can have diagnostic value.

Lemod increases the metabolites of 11- and 17-oxyketocorticosteroids.

Lyophilizate for the preparation of solution for intravenous and intramuscular administration should be used only in inpatient medical institutions

Form release / dosage:

Lyophilizate for the preparation of a solution for intravenous and intramuscular injection, 125 mg (complete with a solvent - 0.9% benzyl alcohol).

Packaging:

The lyophilizate is placed in a vial of colorless glass II of hydrolytic class, sealed with a rubber stopper and sealed with an aluminum cap with a liner in the form of a plastic disc (control of the first opening).

2 ml of solvent in a vial of colorless glass I hydrolytic class. On the ampoule with a blue paint dot and ring.

1 bottle with the drug and 1 ampoule with a solvent is placed in a pack of cardboard along with instructions for use.

Storage conditions:

Store at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001550/08

Date of registration:14.03.2008 / 01.07.2008

Expiration Date:Unlimited

The owner of the registration certificate:Hemofarm ADHemofarm AD Serbia

Manufacturer: & nbsp

HEMOFARM, A.D. Serbia

Representation: & nbspHEMOFARM A.D. HEMOFARM A.D. Serbia

Information update date: & nbsp06.03.2018

Illustrated instructions

Instructions

Lemodus (Lemod)