Dexamethasone - instructions for use, dose, side effects, contraindications

Excipients: glycerol (glycerin distilled) 22.5 mg, disodium edetate (Trilon B) 0.1 mg, sodium hydrogen phosphate dodecahydrate (sodium phosphate disubstituted 12-water) 0.8 mg, water for injection up to 1 ml.

Description:Transparent colorless or light yellow liquid.

Pharmacotherapeutic group:Glucocorticosteroid

ATX: & nbsp

H.02.A.B.02 Dexamethasone

S.01.B.A.01 Dexamethasone

H.02.A.B Glucocorticoids

S.01.B.A Corticosteroids

Pharmacodynamics:

Synthetic glucocorticosteroid is a methylated derivative of fluoride prednisolone. Has anti-inflammatory, antiallergic desensitizing, anti-shock, antitoxic and immunosuppressive action.

Interacts with specific cytoplasmic receptors and forms a complex that penetrates into the nucleus of the cell and stimulates the synthesis of mRNA; the latter induces the formation of proteins,in t.ch. lipocortin, mediating cellular effects. Lipocortin depresses phospholipase A₂, suppresses the release of arachidonic acid and inhibits the biosynthesis of endoperoxides, prostaglandins, leukotrienes, contributing to inflammation processes, allergies, and others.

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 gastrointestinal 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 the activation of gluconeogenesis.

Antagonistic action in relation to vitamin D: "washing away" calcium from bones and increasing its renal excretion.

Anti-inflammatory effect is associated with 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).

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 caused by inhibition of the release of cytokines (interleukin) and interleukin₂, gamma-interferon) from lymphocytes and macrophages.

Suppresses the synthesis and secretion of adrenocorticotropic hormone and, secondarily, the synthesis of endogenous glucocorticosteroids. The peculiarity of the action is a significant inhibition of the pituitary function and a virtually complete absence of mineralocorticosteroid activity.

Doses of 1-1.5 mg / day inhibit the function of the adrenal cortex; the biological half-life is 32-72 hours (the duration of oppression of the hypothalamic-pituitary-cortical adrenal gland system).

The strength of the glucocorticosteroid activity of 0.5 mg of dexamethasone corresponds to approximately 3.5 mg of prednisone (or prednisolone), 15 mg of hydrocortisone, or 17.5 mg of cortisone.

Pharmacokinetics:

Blood is bound (60-70%) with a specific transporter protein - transcortin. Easily passes through the histohematological barriers (including through the blood-brain barrier and placental). In small amounts excreted in breast milk. Metabolised in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites. It is excreted by the kidneys.

Indications:

The drug is used for diseases requiring the introduction of a fast-acting glucocorticosteroid, and also in those cases when oral administration of the drug is impossible:

- endocrine diseases (acute insufficiency of the adrenal cortex, primary or secondary insufficiency of the adrenal cortex, congenital hyperplasia of the adrenal cortex, subacute thyroiditis);

- shock, resistant to standard therapy; anaphylactic shock;

- cerebral edema (with a brain tumor, craniocerebral trauma, neurosurgical intervention, cerebral hemorrhage, encephalitis, meningitis, radiation injury);

- asthmatic status; severe bronchospasm (exacerbation of bronchial asthma, chronic obstructive bronchitis);

- severe allergic reactions;

- rheumatic diseases;

- systemic connective tissue diseases;

- acute severe dermatoses;

- malignant diseases (palliative treatment of leukemia and lymphoma in adult patients, acute leukemia in children, hypercalcemia in patients with malignant tumors, with the impossibility of oral treatment);

- diagnostic study of adrenal hyperfunction;

- blood diseases (acute hemolytic anemia, agranulocytosis, idiopathic thrombocytopenic purpura in adults);

- severe infectious diseases (in combination with antibiotics);

- intraarticular and intrasynovial administration: arthritis of various etiologies, osteoarthritis, acute and subacute bursitis, acute tendovaginitis, epicondylitis, synovitis;

- local application (in the area of pathological education): keloids, discoid lupus erythematosus, annular granuloma.

Contraindications:

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

For intraarticular administration: previous arthroplasty, abnormal bleeding (endogenous or caused by the use of anticoagulants), intraarticular fracture, infection (septic) inflammatory process in the joints and periarticular infections (including history), and also common infectious disease marked periarticular osteoporosis, no signs inflammation of the joint (so-called "dry" joint, such as osteoarthritis without synovitis), bone destruction and severe joint deformity (sharp narrowing of the joint space, ankylosis) , joint instability as the outcome of arthritis, aseptic necrosis of the joints forming the epiphyses of bones.

Carefully:

Parasitic and infectious diseases of viral, fungal or bacterial origin (currently or recently transferred, including the recent contact with the patient) - herpes simplex, herpes zoster (viremicheskaya phase), chicken pox, measles; amoebiasis, strongyloidiasis (or suspected); systemic mycosis; active and latent tuberculosis. The use in severe infectious diseases is permissible only against the background of specific therapy.

Post-vaccination period (period of 8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination. Immunodeficiency conditions (including AIDS or HIV infection).

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).

Diseases of the cardiovascular system, incl. recently suffered myocardial infarction (in patients with acute and subacute myocardial infarction, a necrosis foci may spread, a delay in the formation of scar tissue and, as a consequence, a rupture of the heart muscle), uncompensated chronic heart failure, hypertension, hyperlipidemia.

Endocrine diseases - diabetes (including a violation of tolerance to carbohydrates), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease.

Severe chronic renal and / or hepatic insufficiency, nephrourolythiasis.

Hypoalbuminemia and conditions predisposing to its occurrence.

Systemic osteoporosis, myasthenia gravis gravis, acute psychosis, obesity (III-IV ), poliomyelitis (except for the form of bulbar encephalitis), open and closed angle glaucoma, pregnancy, lactation.

For intraarticular administration: the general severe condition of the patient, the ineffectiveness (or short-term) of the effect of the previous 2 injections (taking into account the individual properties of the glucocorticosteroids used).

Pregnancy and lactation:

During pregnancy (especially in the first trimester) the drug can be applied only when the expected therapeutic effect exceeds the potential risk to the fetus. With prolonged therapy during pregnancy, the possibility of impaired fetal growth is not ruled out. In case of application at the end of pregnancy, there is a risk of atrophy of the adrenal cortex in the fetus, which may require replacement therapy in the newborn.

If it is necessary to carry out treatment with the drug during breastfeeding, then breastfeeding should be discontinued.

Dosing and Administration:

Intra-articular, in the lesion - 0,2-6 mg, with a repetition of 1 time in 3 days or 3 weeks. Intramuscularly or intravenously, 0.5-9 mg / day.

For the treatment of cerebral edema - 10 mg in the first injection, then 4 mg intramuscularly every 6 hours until the symptoms disappear. The dose can be reduced after 2-4 days with a gradual cancellation in the period of 5-7 days after the removal of cerebral edema. Maintenance dose - 2 mg 3 times / day.

To treat shock - intravenously 20 mg in the first administration, then 3 mg / kg for 24 hours in the form of intravenous infusions or intravenously spray-2 to 6 mg / kg as a single injection or 40 mg as a single injection, administered every 2 to 6 hours; possibly intravenous administration of 1 mg / kg once. The shock therapy should be canceled, as soon as the patient's condition stabilizes, the usual duration is not more than 2-3 days. Allergic diseases - intramuscularly in the first injection of 4-8 mg. Further treatment is carried out by oral dosage forms.

With nausea and vomiting, during chemotherapy - intravenously 8-20 mg for 5-15 minutes before the chemotherapy session. Further chemotherapy should be performed using oral dosage forms.

For the treatment of respiratory distress syndrome of newborns - intramuscularly 4 injections of 5 mg every 12 hours for two days.

The maximum daily dose is 80 mg.

For children: for treatment of adrenal insufficiency - intramuscularly at 23 mcg / kg (0.67 mg / sq.m) every 3 days, or 7.8-12 μg / kg (0.23-0.34 mg / m2 / day), or 28-170 μg / kg (0.83-5 mg / sq. m) every 12-24 hours.

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 side of metabolism: delay sodium and water in the body; hypokalemia; hypokalemic alkalosis; negative nitrogen balance, caused by increased protein catabolism, increased appetite, weight gain.

From the cardiovascular system: higher risk of thrombus formation (especially in immobilized patients), arrhythmias, increased blood pressure, development or aggravation of chronic heart failure, myocardial dystrophy, steroid vasculitis.

From the musculoskeletal system: muscle weakness, steroid myopathy, muscle mass reduction, osteoporosis, vertebral compression fractures, aseptic necrosis of the head of the femoral and humerus bones, pathological fractures of long bones.

From the digestive system: nausea, vomiting, erosive-ulcerative lesions of the gastrointestinal tract (which may be the cause of perforations and bleeding), hepatomegaly, pancreatitis, ulcerative esophagitis.

Dermatological reactions: thinning and vulnerability of the skin, petechiae and subcutaneous hemorrhages, ecchymosis, striae, steroid acne, delayed wound healing, increased sweating.

From the central nervous system: increased fatigue, dizziness, headache, mental disorders, seizures and false brain tumor symptoms (increased intracranial pressure with a congestive optic nerve disc).

From the endocrine system: depression of glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, oppression of the adrenal gland function, Itenko-Cushing syndrome (lunar face, obesity of the pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia, striae), delay in sexual development in children.

On the part of the organs of vision: posterior subcapsular cataract, increased intraocular pressure, exophthalmos.

Side effects associated with immunosuppressive action: more frequent occurrence of infections and aggravation of the severity of their course.

Other: allergic reactions.

Local reactions (at the place of administration): hyperpigmentation and leukoderma, atrophy of subcutaneous tissue and skin, aseptic abscess, hyperemia at the injection site, arthropathy.

Overdose:

Symptoms: increased blood pressure, swelling, peptic ulcer, hyperglycemia, impaired consciousness.

Treatment: symptomatic, there is no specific antidote.

Interaction:

Simultaneous use with phenobarbital, rifampicin, phenytoin or ephedrine can accelerate the biotransformation of dexamethasone, thereby weakening its effect.

Hormonal contraceptives increase the effect of dexamethasone.

Simultaneous use with diuretics (especially "loop") can lead to increased excretion of potassium from the body.

With simultaneous administration with cardiac glycosides, the possibility of cardiac arrhythmias increases.

Dexamethasone weakens (less intensifies) the effect of coumarin derivatives, which requires correction of their dose.

Dexamethasone increases the side effect of non-steroidal anti-inflammatory drugs, especially their effect on the gastrointestinal tract (increased risk of erosive ulcerative lesions and bleeding from the gastrointestinal tract).In addition, it reduces the concentration of non-steroidal anti-inflammatory drugs in the blood serum and thereby their effectiveness.

Inhibitors of carbonic anhydrase increase the risk of hypernatremia, edema, hypokalemia, osteoporosis.

Reduces the effectiveness of insulin and oral hypoglycemic drugs, antihypertensive drugs.

Antacids weaken the action of dexamethasone.

In combination with paracetamol leads to an increased risk of hepatotoxicity, due to the induction of hepatic enzymes and the formation of a toxic metabolite of paracetamol.

Simultaneous use of androgens, steroid anabolics contributes to the appearance of edema, hirsutism and acne; estrogens, oral contraceptives - leads to a decrease in clearance, an increase in the toxic effects of dexamethasone.

The risk of developing cataracts is increased when antipsychotic drugs (antipsychotics) and azathioprine are used against dexamethasone.

Simultaneous appointment with M-holinoblokatorami (including antihistamines, tricyclic antidepressants) and nitrates contribute to the development of glaucoma.

With simultaneous use with live antiviral vaccines and against other types of immunizations, increases the risk of virus activation and the development of infections.Sodium-containing drugs or supplements increase the likelihood of edema and increased blood pressure.

Amphotericin B increases the risk of heart failure.

In combination with anticoagulants and thrombolytics, the risk of ulcers of the gastrointestinal tract and bleeding increases.

Reduces the concentration in the plasma of salicylates (increases the excretion of salicylates).

Increases the metabolism of mexiletine, reducing its concentration in the plasma.

Special instructions:

Children who are in contact with sick measles or chickenpox during the treatment period prophylactically prescribe special immunoglobulins.

In children during growth, glucocorticosteroids should be used only in absolute indications and under the strictest supervision of a physician.

It should be borne in mind that in patients with hypothyroidism, the clearance of glucocorticosteroids decreases, and in patients with thyrotoxicosis, it increases.

Effect on the ability to drive transp. cf. and fur:

During treatment, it is not recommended to drive vehicles, as well as engage in activities that require speed of psychomotor reactions and precise movements.

Form release / dosage:

Solution for injection, 4 mg / ml.

Packaging:

1 ml per ampoule of neutral glass.

For 10 ampoules, together with the instruction for use and the ampoule opening opener or ampoule scarifier, is placed in a cardboard box.

5 ampoules per contour cell packaging made of polyvinyl chloride film.

For 1 or 2 contour packs with instructions for use and a knife for opening ampoules or a scarifier ampullum are placed in a pack of cardboard.

When using ampoules with incisions, rings and break points, a scarifier ampoule or a knife for opening ampoules is allowed not to be put.

Storage conditions:

In the dark place at a temperature of 5 to 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001203

Date of registration:11.11.2011

Expiration Date:11.11.2016

The owner of the registration certificate:DALHIMFARM, OJSC DALHIMFARM, OJSC Russia

Manufacturer: & nbsp

DALHIMFARM, OJSC Russia

Representation: & nbspDALHIMFARM, OJSCDALHIMFARM, OJSC

Information update date: & nbsp20.03.2017

Illustrated instructions

Instructions

Dexamethasone (Dexamethasone)