Deperzolon

General characteristics. Structure:

Active agent: a mazipredona a hydrochloride - 30 mg.

Excipients: benzyl alcohol, ethanol (96%), propylene glycol, water for injections.

Pharmacological properties:

Pharmacodynamics. Mazipredon is a synthetic glucocorticosteroid (GKS), to soluble derivatives of Prednisolonum. Has antiinflammatory, immunosuppressive and antiallergic effect. Having easily got in target cells, takes up with GKS receptors in cytoplasm. Free receptors are, usually, tied with a so-called protein of thermal shock (HSP90). After accession to GKS receptors the structure of HSP90 changes, and it leaves a receptor. The last moves to a cell kernel. Multilateral action of GKS is caused by existence of so-called elements of the glucocorticoid answer (CRE) in pro-motor zones of several genes which part "is switched off" as a result of accession of receptors to the CRE while others are in an active state. A key role in this slolshy process is played everywhere by a widespread so-called intracellular factor of a transcription of NF-kB. Various inflammatory mediators activate NF-kB for the purpose of start of products of cytokines. GKS cause a transcription of a protein of IkB which occupies the activated NF-kB and forms with it an inactive cytoplasmatic complex. Except this GKS activate lipokortina, being representatives of other family of proteins, strengthen a transcription of genes of r2-receptors. The essence of action of lipokortin consists in an ingibition of a reaction chain, prostaglandins leading to education, leukotrienes and a factor of activation of thrombocytes. These mediators, usually, increase the vascular permeability leading to hypostases of fabrics, cause migration of leukocytes and formation of deposits of fibrin.

Mazipredon has effect on all stages of inflammatory process among which the ingibition of a phospholipase of A2 and blockade of formation of arachidonic acid due to stimulation of synthesis of polypeptide-inhibitor, so-called lipokortina-1 with the subsequent suppression of biosynthesis of mediators of an inflammation, so-called pleyotropny cytokines of reaction of an acute phase of an inflammation is especially important: interleykina-1, tumor necrosis alpha factor, and also interleykinov-4 and 5. Besides, blocks a transcription of genes of such enzymes of an inflammation as NO синтетаза and cyclooxygenase. Suppresses functions of neutrophils and macrophages, including release of chemical mediators and their effects on capillaries. Stabilizes cellular membranes and organellas (especially liposomal) and increases their resistance to influence of various disturbing factors. Blocking inflammatory reactions in connecting fabric, interferes with formation of cicatricial fabric. Suppresses inflammatory process it is not dependent on its etiology, at excessive or "useless" inflammatory reaction has favorable effect, however constitutes danger at infections because of suppression of protective inflammatory process.

The immunosuppressive effect is carried out thanks to impact of a mazipredon on numerous targets among which suppression of secretion of cytokines is especially important. Suppresses proliferation of lymphocytes, including leukemia lymphocytes, an expression of the Ministry of Taxes and Tax Collection of II on macrophages and adhesive molecules of endothelial cells, causes an eosinopenia and interferes with degranulation of eosinophils and adhesion of neutrophils, interferes with emission by cells of cytokines (mainly interleykina-2 and y-interferon) to both secretion, and prostaglandin E emission, and also blocks collagen synthesis in fibroblasts. High doses of GKS suppress products of antibodies.

Interferes with development of allergic reactions. Reduces quantity of the circulating eosinophils, basophiles and allocation of mediators of an immediate allergy. Interaction of allergens with antibodies remains invariable, however the damaging effects of an inflammation are absent. Influences different types of a metabolism in a human body.

Carbohydrate metabolism: activates a gluconeogenesis (strengthening of absorption of carbohydrate from a GIT, increase in activity глюкозо - 6 - phosphotazy and phosphoenol pyruvatekinase with increase in intake of glucose from a liver in blood), at the same time peripheral utilization of glucose (glucose transport through a cellular membrane) can decrease, leading to a hyperglycemia and sometimes a glucosuria, manifestation of a latent diabetes mellitus.

Protein metabolism: anabolism decreases (reduction of amount of globulins, increase in synthesis of albumine in a liver and kidneys, increase in coefficient albumine/globulin) at invariable or even the amplified intensity of catabolic processes that results in negative nitrogenous balance with an atrophy of muscular tissue. Osteoporosis because of reduction of a protein matrix of a bone tissue, delay of growth at children, a skin atrophy is possible that it at the increased fragility of capillaries results in the increased vulnerability of skin and formation of striya. Healing of wounds and round ulcers is slowed down and happens to formation of fibrous fabric.

Lipometabolism: synthesis of higher fatty acids and triglycerides with an adiposity in the field of a shoulder girdle, on a face and a stomach and its mobilization from a hypodermic fatty tissue of extremities with the subsequent hypercholesterolemia amplifies.

Water and electrolytic exchange (mineralokortikoidny effects): the sodium delay increases in renal tubules, potassium excretion together with urine increases. Reduces a hypercalcemia at excess absorption of calcium from the digestive tract (DT) (a sarcoidosis, intoxication vitamin D), raises calcium excretion with urine with possible formation of stones.

Suppresses feedback гипоталамо - pituitary and adrenal system at long reception (with the subsequent slowed-down recovery) that at the sharp termination of treatment leads to development in the patient of adrenal insufficiency: suppresses synthesis and secretion of AKTG a hypophysis, oppressing thereby synthesis by adrenal glands of endogenous glucocorticosteroids and androgens. Antiinflammatory effect of drug is 4 times stronger, than at a hydrocortisone. Mazipredon has insignificant mineralokortikoidny activity. At intravenous administration renders the expressed effect of Prednisolonum, at intramuscular introduction action comes later.

Pharmacokinetics. It is quickly distributed in an organism at intravenous administration. At intramuscular introduction plasma elimination half-life ~ 3,3 hours. 35-40% of a mazipredon are allocated through kidneys in not changed look.

Indications to use:

States at which parenteral administration of GKS is shown:

- Depressed cases (burn, traumatic, operational, toxic, cardiogenic) - at inefficiency of vasoconstrictors, plasma substituting drugs and other symptomatic therapy.
- Allergic reactions (acute severe forms), hemotransfusionic shock, acute anaphylaxis, anaphylactoid reactions.
- Bronchial asthma (severe form), asthmatic status.
- Intoxication at infectious diseases (at prolonged use of GKS at the same time appoint antibiotics).
- Acute and chronic insufficiency of bark of adrenal glands (in a combination from mineralokortikoida).
- Hepatic coma.

Route of administration and doses:

Adults: at shock, resistant to standard therapy, the single dose makes 30-90 mg intravenously struyno slowly (~ 3 min.) or kapelno. The maximum daily dose - 150-300 mg.

At impossibility of intravenous administration it is possible to enter deeply into a gluteus, at the same time action comes later. In case of need, in addition enter 30-60 mg of drug intravenously or intramusculary.

At other indications a single dose - 30-45 mg intravenously slowly or intramusculary (in a gluteus). At improvement of a state treatment should be continued by the decreasing doses of tablets of Prednisolonum.

Children: at the age of 2-12 months: a single dose of 2-3 mg/kg of body weight intravenously or deeply in a gluteus; at the age of 1-14 years - 1-2 mg/kg of body weight intravenously slowly (~ 3 min.) or are deep in a gluteus. In case of need, in 20-30 minutes the dose can be repeated.

Features of use:

During treatment by Deperzolon (especially long) observation of the oculist, control of arterial pressure, a condition of water and electrolytic balance, and also a picture of peripheral blood and 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 receipt of K+ 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 Deperzolon in high doses appoint to psychoses under strict control of the doctor.

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

In stressful situations during the supporting treatment (for example, surgeries, an injury or infectious diseases) it is necessary to carry out dose adjustment of drug in connection with increase in need for GKS. At sudden cancellation, especially in case of the previous use of high doses, development of a syndrome of "cancellation" (anorexia, nausea, block, generalized musculoskeletal pains, the general weakness), and also an exacerbation of a disease concerning which Deperzolon was appointed is possible.

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

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

At children during prolonged treatment by Deperzolon careful observation of dynamics of growth and development is necessary. To children who during treatment were in contact with patients with measles or chicken pox preventively appoint specific immunoglobulins.

Owing to weak mineralokortikoidny effect for replacement therapy at adrenal insufficiency Deperzolon 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.

Deperzolon with latent infectious diseases of kidneys and urinary tract is capable to cause a leukocyturia in patients that can have diagnostic value.

Deperzolon increases the maintenance of metabolites of 11-and 17 oxyketocorticosteroids.

Side effects:

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

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

From the alimentary system: nausea, vomiting, pancreatitis, steroid stomach ulcer and duodenum, erosive esophagitis, gastrointestinal bleedings and perforation of a wall of digestive tract, increase or loss of appetite, digestion disturbance, meteorism, hiccups. In rare instances - increase in activity of "hepatic" transaminases and an alkaline phosphatase.

From cardiovascular system: arrhythmias, bradycardia (up to a cardiac standstill); development (at predisposed patients) or strengthening of expressiveness of heart failure, change on the electrocardiogram, characteristic of a hypopotassemia, increase in arterial pressure, hypercoagulation, fibrinferments. Patients with an acute and subacute myocardial infarction have a distribution of the center of a necrosis, delay of formation of cicatricial fabric that can lead to a rupture of a cardiac muscle.

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

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

From a metabolism: the increased calcium removal, a hypocalcemia, increase in body weight, negative nitrogenous balance (the increased disintegration of proteins), the increased perspiration.

Caused by mineralokortikoidny activity - a delay of liquid and sodium (peripheral hypostases), a hypernatremia, a gipokaliyemichesky syndrome (a hypopotassemia, arrhythmia, a mialgiya or a spasm of muscles, unusual weakness and fatigue).

From a basic dvigateljnogo of the device: delay of growth and processes of ossification at children (premature closing of epiphyseal regions of growth), osteoporosis (it is very rare - pathological fractures of bones, an aseptic necrosis of a head humeral and a femur), a rupture of sinews of muscles, a steroid myopathy, decrease in muscle bulk (atrophy).

From integuments and mucous membranes: the slowed-down healing of wounds, petechias, ecchymomas, thinning of skin, hyper - or hypopigmentation, steroid eels, striya, tendency to development of a pyoderma and candidiases.

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

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

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

Interaction with other medicines:

Use of a mazipredon along with aerosols of sympathomimetics is contraindicated to children with bronchial asthma. At co-administration of a mazipredon and indirect anticoagulants anticoagulative action of the last can be weakened, is more rare - to amplify; dose adjustment is necessary.

The combination of a mazipredon with anticoagulants and trombolitika increases risk of development of ulcer bleedings from a GIT.

The concomitant use with salicylates is followed by acceleration of removal and decrease in concentration, and at cancellation of a mazipredon - increase in concentration of salicylates in blood with probability of development of side effects, including - developing of gastrointestinal bleeding.

The combination of a mazipredon with diuretics, especially thiazide derivatives and inhibitors of a karboangidraza, Amphotericinum In can lead to strengthening of removal from an organism of K+ and increase in risk of development of heart failure; with natriysoderzhashchy drugs - leads to hypostases and increase in arterial pressure.

Simultaneous use of a mazipredon with antihypertensives. the tableted hypoglycemic drugs and insulin reduces their efficiency; with cardiac glycosides - strengthens risk of development of glikozidny intoxication with development ventricular экстр asystolias as a result of a hypopotassemia.

Hormonal contraceptives strengthen action of a mazipredon.

Simultaneous use of a mazipredon and ethanol or non-steroidal anti-inflammatory drugs increases risk of emergence of erosive cankers and bleedings from a GIT (the drug dose decline can be required).

Emergence of a hirsutism, eels and hypostases is promoted by simultaneous use of a mazipredon with other steroid hormonal drugs (androgens, estrogen, oral contraceptives and steroid anabolic steroids).

Besides, simultaneous use with hormonal contraceptives is followed by strengthening of action of a mazipredon because of decrease in clearance of the last.

The risk of development of a cataract increases at simultaneous use of a mazipredon with antipsychotic means, Carbutamidum and Azathioprinum. Simultaneous use with inductors of microsomal enzymes of a liver (Phenytoinum and barbiturates, ephedrine, rifampicin, theophylline) leads to decrease in concentration and easing of effect of a mazipredon.

Simultaneous use of a mazipredon with M-holinoblokatorami, including antihistaminic drugs, tricyclic antidepressants, and nitrates promotes increase in intraocular pressure.

Reception of a mazipredon during treatment by a pazikvatel leads to decrease in concentration of the last.

The concomitant use with paracetamol increases hepatotoxic effect as a result of induction of hepatic enzymes and formation of a toxic metabolite of paracetamol.

The concomitant use with vitamin D reduces impact of the last on absorbability of calcium in intestines.

At a concomitant use with somatotropic hormone efficiency of the last decreases.

Metabolism amplifies and decrease concentration of an isoniazid and mekselitin in blood at their concomitant use with mazipredony, especially at slow acetylizers.

Inhibitors of a karboangidraza and loopback diuretics can promote development of osteoporosis.

Indometacin forces out мазипредон from communication with albumine and promotes development of osteoporosis.

Ergocalciferol and parathormone interfere with development of a glucocorticosteroid osteopathy.

AKTG strengthens action of a mazipredon.

Cyclosporine and кетоконазол, slowing down metabolism of a mazipredon, in some cases increase its toxicity.

At a concomitant use with Mitotanum and other inhibitors of function of bark of adrenal glands increase in doses of a mazipredon can be required.

Simultaneous use with live antiviral vaccines and other types of immunization promotes activation of viruses with development of infectious diseases.

Antititireoidny preparta reduce, and thyroid hormones increase clearance of a mazipredon.

Contraindications:

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

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

With care it is necessary to appoint drug at the following diseases and states:

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

Pregnancy.
USE DURING PREGNANCY AND BREASTFEEDING
During pregnancy (especially in the I trimester) apply only according to vital indications. At long therapy during pregnancy the possibility of a growth disorder of a fruit is not excluded. In case of use in Sh trimester of pregnancy there is a danger of emergence of an atrophy of bark of adrenal glands at a fruit that can demand performing replacement therapy from the newborn. As GKS get into breast milk, in case of need uses of drug during breastfeeding, feeding by a breast is recommended to be stopped.

Overdose:

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

Storage conditions:

At a temperature of 8-15 °C in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 1 ml of drug in an ampoule from brown glass of the first hydrolytic class. On 3 ampoules in a cardboard pack with the enclosed application instruction.