Description
Release form
Lyophilisate for solution for i / v and v / m administration.
Pharmacological action
Methyluracil is a drug that improves tissue trophism and stimulates the regeneration process.
Has anabolic and anti-catabolic activity, stimulates leukopoiesis. Normalizing nucleic acid metabolism, accelerates cell regeneration processes in wounds, accelerating tissue growth and granulation maturation and epithelization. When applied topically to a wound, it has photoprotective properties.
It has an immunostimulating effect: it stimulates cellular and humoral factors of immunity.
Interacts with specific cytoplasmic receptors (there are receptors for GCS in all tissues, especially many in the liver) with the formation of a complex that induces the formation of proteins (including enzymes that regulate vital processes in cells).
Effect of methylprednisolone on protein metabolism: reduces the amount of globulins in plasma, increases the synthesis of albumin in the liver and kidneys (with an increase in the albumin / globulin coefficient), reduces the synthesis and enhances protein catabolism in muscle tissue.
Effect of methylprednisolone on lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (fat accumulation occurs mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.
Effect of methylprednisolone on carbohydrate metabolism: stabilization of cell membranes (especially lysosomal) and organelle membranes. It acts at all stages of the inflammatory process: it inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin inhibits phospholipase A2, inhibits the liberalization of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, including inflammation, allergies), and the synthesis of pro-inflammatory cytokines (including including interleukin 1, tumor necrosis factor alpha), increases the resistance of the cell membrane to the action of various damaging factors.
The immunosuppressive effect is caused by involution of lymphoid tissue, inhibition of proliferation of lymphocytes (especially T-lymphocytes), inhibition of B-cell migration and the interaction of T- and B-lymphocytes, inhibition of cytokine release (interleukin-1, 2,
Interacts with specific cytoplasmic receptors (there are receptors for GCS in all tissues, especially many in the liver) with the formation of a complex that induces the formation of proteins (including enzymes that regulate vital processes in cells).
Effect of methylprednisolone on protein metabolism: reduces the amount of globulins in plasma, increases the synthesis of albumin in the liver and kidneys (with an increase in the albumin / globulin coefficient), reduces the synthesis and enhances protein catabolism in muscle tissue.
Effect of methylprednisolone on lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (fat accumulation occurs mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.
Effect of methylprednisolone on carbohydrate metabolism: stabilization of cell membranes (especially lysosomal) and organelle membranes. It acts at all stages of the inflammatory process: it inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin inhibits phospholipase A2, inhibits the liberalization of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, including inflammation, allergies), and the synthesis of pro-inflammatory cytokines (including including interleukin 1, tumor necrosis factor alpha), increases the resistance of the cell membrane to the action of various damaging factors.
The immunosuppressive effect is caused by involution of lymphoid tissue, inhibition of proliferation of lymphocytes (especially T-lymphocytes), inhibition of B-cell migration and the interaction of T- and B-lymphocytes, inhibition of cytokine release (interleukin-1, 2, a decrease in eosinophilic infiltration of the submucosal layer of the bronchial epithelium and 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 caliber to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by reducing its production.
Suppresses the synthesis and secretion of ACTH and secondarily the synthesis of endogenous corticosteroids.
Inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.
Indications
shock conditions (burn, traumatic, surgical, toxic, cardiogenic) with the ineffectiveness of vasoconstrictor drugs, plasma replacement drugs and other symptomatic therapy
allergic reactions (acute severe forms), blood transfusion shock, anaphylactic reaction (anaphylactic) including against a background of a brain tumor or associated with surgery, radiation therapy or a head injury)
bronchial asthma (severe form), asthmatic status
SLE, re matoidny
arthritis, acute adrenal insufficiency
thyrotoxic crisis
acute hepatitis, hepatic coma
reduction in inflammation and prevention of cicatricial constrictions (at poisoning cauterizing liquids).
Contraindications
For short-term use for life, the only contraindication is hypersensitivity to methylprednisolone or the components of the drug.
In children during the period of GCS growth, it should be used only according to absolute indications and with careful medical supervision.
With caution, the drug should be prescribed for the following diseases and conditions:
gastrointestinal tract diseases – gastric ulcer and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, recently created intestinal anastomosis, ulcerative ulcer, with the threat of perforation or abscess formation, and diverticulitis s diseases of a viral, fungal or bacterial nature (currently or recently transferred, including recent contact with the patient) – herpes simplex, herpes zoster (viremic phase), chickenpox, measles, amoebiasis, strongyloidosis, systemic mycosis active and latent tuberculosis (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 states (including AIDS or HIV infection)
diseases of the cardiovascular system (including recent myocardial infarction – in patients with acute and subacute myocardial infarction zhno spread necrosis, slowing the formation of scar tissue and thereby, – tearing of the heart muscle), severe chronic heart failure, hypertension, hyperlipidemia
endocrine diseases – diabetes (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itsenko-Kushing’s disease, obesity (III-IV degree)
severe chronic renal and / or liver failure,
nephrourolithiasis and hypoalbuminemia and conditions that predispose to its occurrence srdlkosis acute systemic acute psychosis, polio (except for the form of bulbar encephalitis), open-angle and angle-closure glaucoma
pregnancy.
Use during pregnancy and lactation
During pregnancy (especially in the first trimester), the drug should be used only for health reasons.
Since corticosteroids pass into breast milk, if it is necessary to use the drug during lactation (breastfeeding), breastfeeding is recommended to be discontinued.
Composition
1 vial contains:
Active ingredient: methylprednisolone sodium succinate (in terms of methylprednisolone) 250 mg
Excipient: sodium hydroxide – 12.5 mg
Solvent: water for injection.
Dosage and administration of
I / V (as slow jet injections or infusions), v / m.
Preparation of the solution. An injection is prepared by adding a solvent to the vial of the lyophilisate immediately before use. The prepared solution contains 62.5 mg / ml methylprednisolone.
As an adjunctive therapy for life-threatening conditions, 30 mg / kg iv for at least 30 minutes is administered. The introduction 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 corticosteroids therapy is effective, with exacerbations of the disease and / or with the ineffectiveness of standard therapy.
Recommended treatment regimens
Rheumatic diseases. 1 g / day iv for 1 4 days or 1 g / month iv for 6 months.
Systemic lupus erythematosus. 1 g / day iv for 3 days.
Multiple sclerosis. 1 g / day iv for 3 or 5 days.
Edematous conditions (e.g. glomerulonephritis, lupus nephritis). 30 mg / kg iv every other day for 4 days or 1 g / day for 3, 5 or 7 days.
The above doses should be administered for at least 30 minutes, 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. With chemotherapy, characterized by a slight or moderate vomiting effect, 250 mg iv are administered for at least 5 minutes 1 hour before the administration of the chemotherapeutic drug, at the beginning of chemotherapy, and also after its completion. With chemotherapy, characterized by a pronounced emetic effect, 250 mg iv are administered for at least 5 minutes in combination with appropriate doses of metoclopramide or butyrophenone 1 hour before the administration of the chemotherapeutic drug, then 250 mg iv at the beginning of chemotherapy and after its completion.
For other indications, the initial dose is 10 500 mg iv depending on the nature of the disease. For a short course in severe acute conditions, higher doses may be required. An initial dose not exceeding 250 mg should be administered iv for at least 5 minutes, doses over 250 mg should be administered for at least 30 minutes. Subsequent doses are administered intravenously or intramuscularly, and the duration of the intervals between administrations depends on the patient’s response to therapy and on his clinical condition.
Children should be given lower doses (but not less than 0.5 mg / kg / day), however, when choosing a dose, the severity of the condition and the patient’s response to therapy, and not age and body weight, should be taken into account in the first place.
Side effects of
From the endocrine system: decreased glucose tolerance, steroid diabetes mellitus, manifestation of latent diabetes mellitus, inhibition of adrenal gland function, Itsenko-Cushing’s syndrome (moon-shaped face, pituitary-type obesity, hypertension, dysmenorrhea, dysmenorrhea, weakness, striae), delayed sexual development in children.
From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, gastrointestinal bleeding, perforation of the gastrointestinal wall, impaired digestion, digestion, flatulence, hiccups rarely – increase liver activity.
From the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest) in predisposed patients develops or worsens the severity of heart failure, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis in patients with acute and subacute myocardial infarction, it is possible to spread a focus of necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle.
From the side of the central nervous system and peripheral nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness, anxiety, insomnia, dizziness, vertigo, cerebellum pseudotumor, headache, convulsion.
From the sensory organs: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to the development of secondary bacterial, fungal or viral infections of the eyes, trophic changes in the cornea, exophthalmos, sudden loss of vision (with parenteral administration in the head, neck, nasal concha, scalp, crystals of the drug may be deposited in the vessels of the eye).
Metabolism: increased calcium excretion, hypocalcemia, increased body weight, negative nitrogen balance (increased protein breakdown), increased sweating due to mineralocorticoid activity – fluid and sodium retention (peripheral edema), hypernatremia, hypokalemia syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).
From the side of the musculoskeletal system: growth retardation and ossification processes in children (premature closure of the pineal gland growth zones), osteoporosis (very rarely – pathological bone fractures, aseptic necrosis of the head of the humerus and femur), tendon rupture of the muscles, steroid myopathy, decreased muscle mass (atrophy).
Dermatological reactions: delayed wound healing, petechiae, ecchymosis, thinning of the skin, hyper- or hypopigmentation, steroid acne, striae, tendency to develop pyoderma and candidiasis.
Allergic reactions: skin rash, itching, anaphylactic shock, local allergic reactions.
Local reactions during parenteral administration: burning, numbness, pain, tingling at the injection site, infection of the injection site rarely – necrosis of surrounding tissues, scarring at the injection site, atrophy of the skin and subcutaneous tissue with i / m administration (introduction into the deltoid muscle is especially dangerous )
Other: the development or exacerbation of infections (the appearance of this side effect is facilitated by the jointly used immunosuppressants and vaccination), leukocyturia, withdrawal syndrome, flushing of the head.
Drug Interaction
Concurrent administration of carbamazepine with CYP3A4 inhibitors may lead to increased plasma concentrations and adverse reactions.
Co-administration of CYP3A4 inducers may accelerate carbamazepine metabolism, reducing its concentration in the blood plasma and reducing the therapeutic effect on the contrary, their abolition may reduce the rate of biotransformation of carbamazepine and lead to an increase in its concentration.
Increase the concentration of carbamazepine in plasma: verapamil, diltiazem, felodipine, dextropropoxyphene, viloxazine, fluoxetine, fluvoxamine, cimetidine, acetazolamide, danazol, desipramine, nicotinamide (high in adults, high erythrocytes) , azoles (itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, isoniazid, propoxyphene, grapefruit juice, viral protease inhibitors used in HIV therapy (eg, ritonavir) – dose adjustment is required or monitoring of carbamazepine plasma concentrations.
Felbamate decreases the plasma concentration of carbamazepine and increases the concentration of carbamazepine-10,11-epoxide, with simultaneous decrease in the serum serum concentration of felbamate.
Concentration of carbamazepine is decreased by phenobarbital, phenytoin, primidone, metsuximide, fensuximide, theophylline, rifampicin, cisplatin, doxorubicin, possibly clonazepam, valpromide, valproic acid, oxcarbazepen
There is a possibility of displacement of valproic acid and primidone of carbamazepine from association with plasma proteins and increasing the concentration of pharmacologically active metabolite (carbamazepine-10,11-epoxide). When combined with Finlepsin with valproic acid, a coma or confusion may occur in exceptional cases.
Isotretinoin alters the bioavailability and / or clearance of carbamazepine and carbamazepine-10,11-epoxide (monitoring of carbamazepine plasma concentration is required).
Carbamazepine may reduce plasma concentrations (reduce or even completely offset effects), which may require dosage adjustments of the following drugs: clobazam, clonazepam, digoxin etosuximide, primidone, valproic acid, alprazolin, CX (prednisolacin, tsX) ), haloperidol, methadone, oral preparations containing estrogens and / or progesterone (selection of alternative contraceptive methods required), theophylline, oral anticoagulants (warfarin, fenprok ÃÃÃ , dykumarola), lamotrigine, topyramata, tricyclic antydepressantov (imipramine, amitriptyline, nortryptylyna, clomipramine), clozapine, felbamate, tiagabine, oxcarbazepine, protease inhibitors used in the treatment of HIV infection (indinavir, ritonavir, saquinavir), calcium channel blockers (dihydropyridine group, eg felodipine), itraconazole, levothizolanxazole, levothiazolan
It is possible to increase or decrease the level of phenytoin in the blood plasma against carbamazepine and increase the level of mefenitoin.
The simultaneous use of carbamazepine and lithium preparations may exacerbate the neurotoxic effects of both active substances.
Tetracyclines may weaken the therapeutic effect of carbamazepine.
When used together with paracetamol, the risk of its toxic effects on the liver increases and therapeutic efficacy decreases (acceleration of paracetamol metabolism).
Concurrent administration of carbamazepine with phenothiazine, pimozide, thioxanthenes, molindone, haloperidol, maprotilin, clozapine, and tricyclic antidepressants leads to increased central nervous system depressant effects and weakening of the antisense effect.
MAO inhibitors increase the risk of developing hyperpyrethic crises, hypertensive crises, convulsions, fatalities (MAO inhibitors should be discontinued for at least 2 weeks before carbamazepine administration or, if the clinical situation permits, even for a longer period).
Concurrent administration with diuretics (hydrochlorothiazide, furosemide) can lead to hyponatremia accompanied by clinical manifestations.
Reduces the effects of non-depolarizing muscle relaxants (pancuronium). In the case of such a combination, there may be a need to increase the dose of muscle relaxants, and careful monitoring of the patient’s condition is required, due to the possibility of faster termination of muscle relaxants.
Carbamazepine reduces ethanol tolerance.
Myelotoxic drugs increase the manifestation of hematotoxicity of the drug.
Accelerates the metabolism of indirect anticoagulants, hormonal contraceptives, folic acid, praziquantel, can enhance the elimination of thyroid hormones.
Accelerates the metabolism of anesthetic agents (enflurane, halothane, fluorothane) and increases the risk of hepatotoxic effects.
Increases the formation of nephrotoxic metabolites of methoxyflurane.
Increases the hepatotoxic effect of isoniazid. ephedrine) leads to a decrease in its concentration (increase in metabolic rate)
with diuretics (especially thiazide-like and carbonic anhydrase inhibitors) and amphotericin B leads to increased excretion of potassium and increase the risk of cardiac insufficiency and sodium-containing drugs contributes to the development of edema and increased blood pressure
with cardiac glycosides leads to a decrease in their tolerability and increase the likelihood of development of ventricular Ñkstrasytolyy eat (because of the v z vaemoy hypokalemia)
with anticoagulants nepryam my promotes oslablenyyu (less frequently GAIN) s action (Requires correction doz )
with anticoagulants and thrombolytics lead for the development of risk Increase krovotechenyy IZ ulcers in the digestive tract with
ethanol and NSAIDs increases the risk of erosive-ulcerative lesions in the gastrointestinal tract and the development of bleeding (in combination with NSAIDs in the treatment of arthritis may reduce the dose of ACS due to the summation of therapeutic effect)
with indomethacin increases the risk of side effects with albumins)
with paracetamol increases the risk of hepatotoxicity (induction of liver enzymes and the formation of a toxic metabolite of paracetamol)
with acetyls lycic acid accelerates its excretion and lowers blood concentration (when methylprednisolone is withdrawn, the level of salicylates in the blood increases and the risk of side effects increases)
with insulin and oral hypoglycemic drugs, antipyretic drugs decreases their effectiveness
with vitamin D decreases its effect on calcium absorption in the intestines
with STG decreases the effectiveness of the last
with praziquantel decreases the concentration of the last
with m-holinoblocator drugs (including antihistamines) isoniazid and mexiletine increase their metabolism (especially in slow acetylators), which leads to a decrease in their plasma concentrations.
ACTH enhances the action of methylprednisolone.
Ergocalciferol and parathyroid hormone prevent the development of osteopathy caused by methylprednisolone.
Cyclosporine and ketoconazole, while slowing the metabolism of methylprednisolone, can in some cases increase its toxicity.
The simultaneous administration of androgens and steroid anabolic drugs with methylprednisolone contributes to the development of peripheral edema, hirsutism and the appearance of acne.
Estrogens and oral estrogen-containing contraceptives reduce the clearance of methylprednisolone, which may be accompanied by an increase in the severity of its action.
Mitotane and other inhibitors of adrenal cortex function may necessitate an increase in the dose of methylprednisolone.
When used with live antiviral vaccines and other immunizations, increases the risk of virus activation and infection.
Immunosuppressants increase the risk of infection and lymphoma or other lymphoproliferative disorders associated with the Epstein-Barr virus.
Antipsychotics (neuroleptics) and azathioprine increase the risk of cataracts with methylprednisolone.
Concurrent administration of antacids reduces the absorption of methylprednisolone.
When used with antithyroid drugs, it decreases, and with thyroid hormones, the clearance of methylprednisolone increases.
Pharmaceutical Interaction
Pharmaceutical incompatibility of methylprednisolone with other injectable drugs is possible. It is recommended to enter it separately from other preparations (in / in bolus, or through another dropper, as the second solution).
Overdose
Symptoms: The side effects described above may increase.
Treatment: symptomatic. The dose of Metipred should be reduced.
Storage conditions
At a temperature of 15 ° to 25 ° C.
Expiration
5 Chron
Deystvuyuschee substances
methylprednisolone
Dosage Form A dosage form
solution
for injection and infusion
Orion Corporation, Finland
