Composition, form of production and packaging
Lyophilizate for the preparation of a solution for intravenous and / or injection in the form of powder or a porous mass of white or almost white; solvent in the form of a clear, colorless solution.
1 f.
methylprednisolone sodium succinate 662.96 mg,
which corresponds to the content of methylprednisolone 500 mg
Excipients: sodium dihydrogen phosphate dihydrate - 6.4 mg, sodium hydrogen phosphate - 69.6 mg.
Solvent: benzyl alcohol - 9 mg, water d / u - up to 1 ml.
Vials of colorless glass with a capacity of 20 ml (1) complete with a solvent (amp 4 ml 1 pc.) - plastic pallets (1) - cardboard packs.
Lyophilizate for the preparation of a solution for intravenous and / or injection in the form of powder or a porous mass of white or almost white; solvent in the form of a clear, colorless solution.
1 f.
methylprednisolone sodium succinate 1325.91 mg,
which corresponds to the content of methylprednisolone 1000 mg
Excipients: sodium dihydrogen phosphate dihydrate - 12.8 mg, sodium hydrophosphate - 139.2 mg.
Solvent: benzyl alcohol - 9 mg, water d / u - up to 1 ml.
Vials of colorless glass with a capacity of 20 ml (1) complete with a solvent (amp 8 ml 1 pc.) - plastic pallets (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Synthetic GCS, dehydrogenated hydrocortisone analog. Has anti-inflammatory, anti-allergic, anti-shock and immunosuppressive action. Interacts with specific cytoplasmic receptors and forms a complex penetrating into the nucleus of the cell and stimulating the synthesis of mRNA; the latter induces the formation of proteins, incl. lipocortin, mediating cellular effects. Lipocortin depresses phospholipase A2, inhibits the liberation of arachidonic acid and inhibits the biosynthesis of endoperoxides, prostaglandins, leukotrienes, contributing to inflammation processes, allergies, etc.
The anti-inflammatory effect is associated with the inhibition of eosinophil release 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 and membranes of organelles (especially lysosomal).
It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.
The antiallergic effect is caused by a decrease in the number of circulating eosinophils, which leads to a decrease in the release of mediators of immediate allergy;reduces the effect of mediators of allergy on effector cells.
Immunodepressive effect is due to inhibition of the release of cytokines (interleukin-1,2, gamma-interferon) from lymphocytes and macrophages.
Protein metabolism: reduces the amount of protein in the plasma (due to globulins) with an increase in the albumin / globulin ratio, increases the synthesis of albumins in the liver and kidneys; enhances protein catabolism in muscle tissue.
Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (accumulation of fat mainly in the area of ​​the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.
Carbohydrate metabolism: increases the absorption of carbohydrates from the digestive tract; increases the activity of glucose-6-phosphatase, leading to an increase in the intake of glucose from the liver into the blood; increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases leading to activation of gluconeogenesis.
Water-electrolytic metabolism: retards sodium and water in the body, stimulates the excretion of potassium (mineralocorticoid activity), reduces the absorption of calcium from the digestive tract, shows antagonistic action against vitamin D: "washing away" of calcium from the bones and increasing its renal excretion.
Suppresses the synthesis and secretion of ACTH and, again, the synthesis of endogenous GCS.
PHARMACOKINETICS
Suction and distribution
Methylprednisolone sodium succinate is highly soluble in water, well absorbed and has a quick and lasting effect. After intramuscular injection, the absorption is complete and fast enough. Bioavailability with intramuscular injection - 89%.
C max methylprednisolone in blood plasma (about 20 Ојg / ml) is reached about 15 minutes after IV injection of the drug at a dose of 30 mg / kg body weight for 20 minutes, or 1 g for 30-60 minutes. After a / m introduction of 40 mg after 2 hours, C max methylprednisolone in blood plasma is equal to 34 Ојg / 100 ml.
Binding to plasma proteins is about 62%.
Metabolism and excretion
Metabolized, mainly in the liver. Its metabolites (keto- and hydroxy compounds) are hormonally inactive and are excreted mainly by the kidneys. About 85% of the administered dose is excreted within 24 hours by the kidneys and about 10% by the intestine.
T 1/2 from the blood plasma is approximately 2.3-4 hours, the duration of action is 12-36 hours. After the / m administration, the drug is present in the blood plasma for a longer period than after the iv introduction if an equivalent amount of methylprednisolone . Taking into account the mechanism of action of glucocorticosteroids, we can assume that these differences are of minimal clinical significance.
INDICATIONS
- endocrine disorders - acute failure of the adrenal cortex;
- rheumatic diseases: acute rheumatism; collagenosis - with exacerbation or for maintenance therapy in systemic lupus erythematosus;
- dermatological diseases - pemphigus, severe erythema multiforme, exfoliative dermatitis, diffuse neurodermatitis, severe psoriasis, severe seborrheic dermatitis;
- bronchial asthma, asthmatic status;
- allergic diseases - severe or resistant to standard therapy: atopic dermatitis, serum sickness, hypersensitivity to medicines, laryngeal edema, urticaria, anaphylactic shock;
- Gastrointestinal diseases - acute stage of ulcerative colitis;
- edema of the brain - to treat cerebral edema caused by brain tumors, head injuries, craniocerebral operations;
- organ transplantation - to prevent the reaction of rejection of the transplanted organ;
- severe shock (hemorrhagic, traumatic, septic) resistant to standard therapy;
- Reduction of inflammatory phenomena and prevention of cicatricial narrowing during poisoning with cauterizing fluids;
- Hematological diseases - acquired autoimmune hemolytic anemia, congenital hypoplastic anemia, erythroblastopenia, idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults;
- for palliative treatment of neoplastic diseases, incl. acute or chronic leukemia and lymphoma in adults, acute leukemia in children.
DOSING MODE
The drug is used iv / (in jet or drip) or in / m. The dose of the drug and the duration of treatment are determined by the attending physician depending on the severity of the disease and the tolerability of the treatment.
In acute adrenocortical insufficiency, a single dose of the drug is 100-200 mg, daily 300-400 mg.
In case of severe allergic reactions, Ivefore is administered in daily dose of 100-200 mg for 3-16 days.
In bronchial asthma, the drug is administered depending on the severity of the disease and the effectiveness of complex treatment from 75 to 675 mg for a course of treatment of 3 to 16 days; in severe cases, the dose may be increased to 1,400 mg per treatment course and more with a gradual dose reduction.
With asthmatic status, Ivered is administered at a dose of 500-1200 mg / day, followed by a decrease to 300 mg / day and switching to maintenance doses.
In the case of shock resistant to standard therapy , Ivefore, at the beginning of therapy, is usually injected intravenously and then switched to iv drip. If within 10-20 minutes the blood pressure does not increase, repeat the fluid administration of the drug. After excretion from the shock state, iv droplet administration is continued until BP stabilizes. Single dose is 50-150 mg (in severe cases - up to 400 mg). Repeated drug is administered after 3-4 hours. The daily dose can be 300-1200 mg (with a subsequent dose reduction).
When immunosuppression - to prevent the reaction of rejection of the transplanted organ (especially the kidneys) during transplantations - Ivefore is used in doses from 0.5 g to 2 g IV every 24-48 hours.
With edema of the brain , 40-125 mg every 4-6 hours IV or IV for 4-7 days (until the patient's condition is stabilized).
With rheumatoid arthritis and SLE, Ivered is administered in addition to the systemic administration of the drug in a dose of 75-125 mg / day, not more than 7-10 days.
When poisoning with cauterizing liquids with burns of the digestive tract and upper respiratory tract is prescribed in a dose of 75-400 mg / day for 3-18 days. The vein is used as an additional therapy for patients with ulcerative colitis, with doses of 20 mg to 40 mg administered iv drip 3-7 times a week for 2 or more weeks.
In other conditions, the initial dose may vary from 10 mg to 40 mg, depending on the clinical picture. Large doses are usually applied for a short period of time.
Children are prescribed in a dose of 0.8-1.5 mg / kg body weight / day.
If it is impossible to / in the introduction, Ivered is given in / m in the same doses. Dose reduction and discontinuation of drug treatment should always be done gradually.
After arresting the acute condition, prednisolone is given intravenously in tablets, followed by a gradual decrease in the dose.
These doses must always be strictly individual. The drug should not be mixed with other drugs in the same syringe.
Preparation of the injection solution: the solvent is added to the lyophilizate in the ampoule and the resulting solution is mixed with a different amount of the infusion solution-5% dextrose, isotonic saline or 5% dextrose in isotonic saline.
SIDE EFFECT
The frequency of development and severity of side effects depends on the duration of application, the amount of dose used, and the possibility of observing the circadian rhythm of the appointment of Iwepred.
When applying the Yvespred, the following may be noted:
On the part of the endocrine system: a decrease in glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes, acne, oppression of adrenal function, Itenko-Cushing syndrome (lunar face, obesity of the pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, striae ), delay in sexual development in children.
On the part of the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, bleeding and perforation of the digestive system, increased or decreased appetite, digestive disorders, flatulence, hiccough.
From 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 cerebellum, headache.
From the side of the organ of vision: 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 infections of the eyes, trophic changes in the cornea, exophthalmos.
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 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.
On the part of the skin and mucous membranes: deterioration of wound healing, 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 reactions with 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, withdrawal syndrome.
With iv introduction: arrhythmias, "tides" of blood to the face, convulsions.
CONTRAINDICATIONS
- for short-term use according to vital indications, the only contraindication is hypersensitivity to the Ivepred.
It is not recommended to apply the drug :
- in patients with acute and subacute myocardial infarction, because the use of GCS in them can lead to the spread of necrosis, slowing the formation of scar tissue and, consequently, to rupture of the heart muscle;
- in newborns. this preparation contains benzyl alcohol. It has been established that benzyl alcohol can cause "asphyxia syndrome" with death in preterm neonates.
With caution the drug should be administered in immunodeficient conditions (including AIDS or HIV), diseases of the cardiovascular system (including recent myocardial infarction, severe chronic heart failure, arterial hypertension), severe chronic renal failure and liver failure, urolithiasis, newly created intestinal anastomosis, peptic ulcer of stomach and duodenum, ulcerative colitis with perforation threat, diverticulitis, esophagitis, gastritis, peptic ulcer diabetes mellitus (including predisposition), parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transferred, and also including recent contact with a patient); closed-angle glaucoma, hyperlipidemia, hyperthyroidism, hypothyroidism, Itenko-Cushing's disease, hypoalbuminemia or conditions predisposing to its occurrence (cirrhosis, nephrotic syndrome), myasthenia gravis, osteoporosis, acute psychosis, obesity (III-IV st).
In children during the growth period, the drug should be used only under absolute indications and under the strictest supervision of the treating physician.
PREGNANCY AND LACTATION
When pregnancy (especially in the first trimester) is used for life indications.
Since SCS is excreted in breast milk, if it is necessary to use the drug during breastfeeding, it is recommended to stop breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution should apply the drug with hypoalbuminemia or conditions predisposing to its occurrence (nephrotic syndrome).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution should apply the drug with hypoalbuminemia or conditions predisposing to its occurrence (cirrhosis of the liver)
APPLICATION FOR CHILDREN
It is not recommended to use the drug in newborns. this preparation contains benzyl alcohol. It has been established that benzyl alcohol can cause a "choking syndrome" with a fatal outcome in premature newborns.
Children are prescribed in a dose of 0.8-1.5 mg / kg body weight / day.
In children during the growth period, the drug should be used only under absolute indications and under the strictest supervision of the attending physician.
SPECIAL INSTRUCTIONS
Before starting treatment, the patient should be examined for possible contraindications. Clinical examination should include examination of the cardiovascular system, radiology examination of the lungs, examination of the stomach and duodenum, urinary system, vision organs; the control of the general analysis of a blood, a level of a glycemia, the maintenance of electrolytes in a plasma.
The effect of the drug is enhanced in patients with hypothyroidism and liver cirrhosis.
The drug can enhance existing emotional instability, mental disorders or psychosis. When referring to a psychosis in an anamnesis, Ivepren in high doses is prescribed under the strict supervision of a doctor.
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 response to an increase in the need for GCS.
It should be carefully monitored for patients within a year after the end of the long-term therapy of Iweprad in connection with the possible development of a relative insufficiency of the adrenal cortex in stressful situations.
In case of sudden cancellation, especially in case of prior application of high doses, there may be a syndrome of "cancellation" (not caused by hypocorticism: anorexia, nausea, blocking, generalized musculoskeletal pain, general weakness); adrenal insufficiency; as well as exacerbation of the disease, about which he was appointed Ivepred.
During Ivepreda treatment should not be vaccinated due to the reduction of its effectiveness and possible neurological complications.
Assigning Ivepred during intercurrent infections, septic conditions, and tuberculosis, treatment with antibiotics is necessary to simultaneously bactericidal action.
Children during prolonged treatment need careful monitoring of the dynamics of growth and development. Children who were in contact with sick measles or chickenpox during the treatment period prophylactically prescribe specific immunoglobulins.
During treatment Ivepredom (especially long) necessary observation oculist, control of blood pressure and water and electrolyte balance as well as peripheral blood picture and blood glucose level. Food must be rich in potassium, protein, vitamins, a small amount of the content of fats, carbohydrates and salts.
Impact on the ability to drive vehicles and mechanisms
During the period of treatment should refrain from activities potentially hazardous activities that require attention, speed of motor and mental reactions (including driving a car or control mechanisms).
OVERDOSE
May increase the side effects described above.
It is necessary to reduce the dose Ivepreda. Treatment simtomaticheskoe.
DRUG INTERACTION
The simultaneous use of phenobarbital, rifampicin, phenytoin or ephedrine Ivepreda leads to a weakening effect.
The simultaneous use of diuretics (particularly "loop") may lead to increased potassium excretion from the body.
While the appointment of cardiac glycosides worsens their tolerance and increase the possibility of cardiac arrhythmias (due to induced hypokalemia).
Ivepred weakens (less amplifies) the action of coumarin derivatives that requires correction of the dose.
Ivepred intensifies the side effects of NSAIDs, especially their effects on the gastrointestinal tract (increased risk of erosive and ulcerative lesions and bleeding from the gastrointestinal tract); reduces the concentration of NSAIDs in the serum, thereby reducing their effectiveness.
Carbonic anhydrase inhibitors, while the use Ivepredom increase the risk of hypokalemia, osteoporosis.
Ivepred reduces the efficiency of insulin and of oral hypoglycemic drugs, antihypertensive drugs.
Ivepred reduces the concentration of praziquantel.
In combination with paracetamol leads to increased risk of hepatotoxicity due to liver enzyme induction and formation of toxic metabolites of paracetamol.
The simultaneous use of androgens, anabolic steroids, promotes the appearance of peripheral edema, hirsutism and acne; estrogens, oral contraceptives - leads to a decrease in clearance and increase the action Ivepreda, an increase in its toxic effects.
The risk of developing cataracts increases with the use on the background Ivepreda antipsychotic drugs (neuroleptics) and azathioprine.
Simultaneous administration of medicine with m-anticholinergic action (including antihistamines, tricyclic antidepressants) and nitrate promotes development of glaucoma.
While the use of amphotericin B increases the risk of developing heart failure.
In combination with anticoagulants and thrombolytics increases the risk of gastrointestinal ulcers and bleeding.
Ivepred mexiletine increases metabolism, reducing its concentration in plasma.
While the use of live virus vaccines and immunization compared to other types of activation increases the risk of viruses and the development of infections.
Sodium-containing medications or supplements increase the likelihood of peripheral edema and increase in blood pressure.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, protected from light at a temperature of no higher than 25 В° C. The term of validity - 3 years.
