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

Dexamethasone is a synthetic hormone of the adrenal cortex, a glucocorticosteroid (GCS), a methylated derivative of fluoride prednisolone. Has anti-inflammatory, antiallergic, desensitizing, anti-shock, antitoxic and immunosuppressive action.

Interacts with specific cytoplasmic receptors of glucocorticosteroids with the formation of a complex that penetrates into the nucleus of the cell and stimulates the synthesis of matrix ribonucleic acid, the latter induces the formation of proteins,including lipocortin, mediating cellular effects. Lipocortin depresses phospholipase A2, inhibits the release of arachidonic acid and inhibits the synthesis of endoperoxides, prostaglandins, leukotrienes, which promote inflammation, allergies, etc.

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 occurs 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 (GIT); increases the activity of glucose-6-phosphatase, which leads 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, which leads to the activation of gluconeogenesis.

Water-electrolyte exchange: retards 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, "wash out" Sa²⁺ from bones, increases excretion of Ca²⁺ kidneys.

Anti-inflammatory effect is associated with inhibition of eosinophil release by inflammatory mediators; inducing lipocortin formation and reducing the number of mast cells producing hyaluronic acid; with a decrease in the permeability of capillaries; stabilization of cell membranes and membranes of organelles (especially lysosomal).

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

In chronic obstructive pulmonary disease action is based mainly on inhibition of inflammatory processes,oppression of the development or prevention of edema of the mucous membranes, inhibition of eosinophilic infiltration of the submucosal layer of the bronchial epithelium, deposition of circulating immune complexes in the mucosa of the bronchi, and 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 due to oppression or reduction of its production.

Anti-shock and antitoxic action is associated with an increase in blood pressure (BP) due to an increase in the concentration of circulating catecholamines and restoration of the sensitivity of adrenoreceptors to them, as well as vasoconstriction), a decrease in the permeability of the vascular wall, membrane-protective properties, activation of liver enzymes involved in the metabolism of endo- and xenobiotics.

Immunodepressive effect due to inhibition of the release of cytokines (interleukin-1 and interleukin-2, gamma interferon) from lymphocytes and macrophages. Dexamethasone has a 30-fold more pronounced effect than endogenous cortisol.Therefore, it is a more potent inhibitor of the secretion of corticotropin-releasing hormone and ACTH.

In pharmacological doses depresses the hypothalamic-pituitary-adrenal system, promotes the development of secondary adrenal insufficiency. Suppresses the synthesis and release of pituitary adrenocorticotropic hormone (ACTH) and the second - the synthesis of endogenous GCS.

Oppressing the secretion of thyroid-stimulating hormone and follicle-stimulating hormone.

Suppresses the release of beta-lipotropin, but does not reduce the content of circulating beta-endorphin.

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

It increases the excitability of the central nervous system, reduces the number of lymphocytes and eosinophils, increases erythrocytes (by stimulating the production of erythropoietins).

A feature of the action is a significant inhibition of the pituitary function and a virtually complete absence of mineralocorticoid activity.

Pharmacokinetics:

Absorption

The maximum concentration of dexamethasone in the blood plasma is reached only 5 minutes after intravenous administration and 1 hour after intramuscular injection.

Distribution

The connection with plasma proteins (mainly with albumins) is 77%. Penetrates through blood-brain and placental barriers. The half-life (T_1/2) from the plasma is 190 min.

Metabolism

Metabolised in the liver. A small amount of dexamethasone is metabolized in the kidneys and other organs.

Excretion

Up to 65% of the dose is excreted by the kidneys within 24 hours.

The time of development of the clinical effect

With intravenous application, the effect develops rapidly; with intramuscular application, the clinical effect develops after 8 hours.

The action is prolonged: from 17 to 28 days after intramuscular administration and from 3 days to 3 weeks after topical application.

With local injection into the joints or soft tissues (in the lesion), absorption is slower than with intramuscular application.

Indications:

Substitution therapy with adrenocortical insufficiency (in combination with sodium chloride and / or mineralocorticosteroids): acute adrenal cortex insufficiency (Addison's disease, bilateral adrenalectomy); the relative insufficiency of the adrenal cortex, which develops after the cessation of treatment with SCS; primary or secondary insufficiency of the adrenal cortex.

Symptomatic and pathogenetic therapy of other diseases requiring the introduction of a fast-acting glucocorticosteroid, as well as in cases when oral administration of the drug is impossible:

- endocrine diseases: congenital hyperplasia of the adrenal cortex, subacute thyroiditis;

- shock (burn, traumatic, operational, toxic) - with ineffectiveness of vasoconstrictors, plasma-substituting drugs and other symptomatic therapy;

- cerebral edema (only after confirming the symptoms of increased intracranial pressure by the results of magnetic resonance or computed tomography) due to brain tumor, craniocerebral trauma, neurosurgical intervention, cerebral hemorrhage, encephalitis, meningitis, radiation injury);

- asthmatic status; severe bronchospasm (exacerbation of bronchial asthma);

- severe allergic reactions, anaphylactic shock;

- 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 inpatients with malignant tumors, with the impossibility of oral treatment;

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

- in ophthalmic practice (subconjunctival, retrobulbar or parabulbar injection): keratitis, keratoconjunctivitis without epithelial damage, iritis, iridocyclitis, blepharitis, blepharoconjunctivitis, scleritis, episcleritis, inflammatory process after eye injuries and surgical interventions, sympathetic ophthalmia, immunosuppressive treatment after corneal transplantation;

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

- poisoning with cauterizing fluids (reducing inflammation and preventing cicatricial narrowing).

Contraindications:

For short-term use of "vital" indications, the only contraindication is hypersensitivity to any of the components of the drug.

The period of breastfeeding, systemic mycoses, the simultaneous use of live and weakened vaccines with immunosuppressive doses of the drug Dexamethasone.

Carefully:

Carefully the drug should be administered in the following diseases and conditions: systemic parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transferred, including recent contact with a patient) - herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amoebiasis, strongyloidiasis (or suspected); active or latent tuberculosis. Application in severe infectious diseases is permissible only against the background of specific antimicrobial therapy.

The vaccination period (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.

Liver failure.

Hypoalbuminemia and conditions predisposing to its occurrence.

Diseases of the cardiovascular system (CVS),including recently suffered myocardial infarction, decompensated chronic heart failure (CHF), hypertension, hyperlipidemia.

Endocrine diseases - diabetes (including impaired tolerance to carbohydrates), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease, obesity III-IV degree.

Severe chronic renal failure, nephrourolythiasis.

Systemic osteoporosis, myasthenia gravis gravis, poliomyelitis (except for the form of bulbar encephalitis), epilepsy, "steroid" myopathy.

Acute psychosis, severe affective disorders (including in the anamnesis, especially "steroid" psychosis).

Open and closed angle glaucoma, herpes of the eye (risk of corneal perforation).

Pregnancy.

Elderly patients - in connection with a high risk of osteoporosis and hypertension.

In children during the growth period, the drug Dexamethasone It should be used only under absolute indications and under especially careful supervision of the doctor.

Pregnancy and lactation:

Dexamethasone penetrates the placenta and can reach high concentrations in the fetus. During pregnancy (especially in the first trimester) or in women planning pregnancy, taking the drug Dexamethasone is shown if the expected therapeutic effect of the drug exceeds the risk of negative effects on the mother and fetus. Dexamethasone should be prescribed in pregnancy only on absolute indications.

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.

A small amount of dexamethasone penetrates into breast milk. If treatment with the drug is necessary during breastfeeding, breastfeeding should be discontinued, as this may delay the growth of the child and reduce the secretion of its endogenous corticosteroids.

Dosing and Administration:

The dosage regimen is individual and depends on the indications, the patient's condition and his reaction to therapy.

The drug is administered intravenously (iv) slowly struino or drip (with acute and urgent conditions); intramuscularly (intramuscularly); possibly also local (in pathological formation) and subconjunctival, retrobulbar or parabulbar injection.

To prepare a solution for intravenous infusion, an isotonic solution of sodium chloride or 5% solution of dextrose.

The drug is administered intravenously and / or in a dose of 0.5-24 mg / day in 2 divided doses (equivalent to 1 / 3-1 / 2 oral dose) as short as possible in the lowest effective dose, and the treatment is gradually withdrawn. Long-term treatment should be carried out at a dose not exceeding 0.5 mg / day. In / m in the same place is injected no more than 2 ml of solution.

When urgent conditions are used in higher doses: the initial dose is 4-20 mg, which is repeated until the desired effect is achieved, the total daily dose rarely exceeds 80 mg. After achieving a therapeutic effect dexamethasone Enter 2-4 mg, if necessary, followed by a gradual withdrawal of the drug.

To maintain a long-term effect, the drug is injected every 3-4 hours or as a continuous drip infusion. After relief of acute conditions, the patient is transferred to dexamethasone intake.

Doses of the drug for children (IM):

The dose of the drug during replacement therapy (with adrenal cortex deficiency) is 0.0233 mg / kg body weight or 0.67 mg / m² body surface area divided into 3 doses, every 3rd day or 0.00776-0.01165 mg / kg body weight or 0.233-0.335 mg / m² body surface area daily. For other indications, the recommended the dose ranges from 0.02776 to 0.1666 mg / kg body weight or 0.833 to 5 mg / m² body surface area 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.

Disorders from the endocrine system: reduced glucose tolerance, "steroid" diabetes or a manifestation of latent diabetes mellitus, adrenal suppression, Cushing's syndrome (moon face, obesity, pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, "steroid" striae), delay sexual development in children.

Disorders from the hematopoiesis system: moderate leukocytosis, lymphopenia, eosinopenia, polycythemia.

Disorders from the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, bleeding and perforation of the intestinal or stomach wall, increased or decreased appetite, flatulence, hiccough, abdominal pain,a feeling of discomfort in the epigastric region. In rare cases - increased activity of "liver" transaminases and alkaline phosphatase.

Heart Disease: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of CHF; changes in the electrocardiogram, characteristic of hypokalemia. 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.

Vascular disorders: increased blood pressure, hypercoagulation, thrombosis; with iv introduction: "tides" of blood to the face, vasculitis, increased fragility of capillaries.

Disturbances from the nervous system: increased intracranial pressure, dizziness, vertigo, pseudotumor of the cerebellum, headache, convulsions.

Disorders from the psyche: nervousness or anxiety, insomnia, emotional lability, delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, suicidal tendencies.

Impaired sensory organs: sudden loss of vision (with parenteral administration in the area of the head, neck, nasal concha, scalp may deposition of drug crystals 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 of the cornea; exophthalmos; chemosis, ptosis, mydriasis, corneal perforation, central serous chorioretinopathy.

Metabolic disorders: increased excretion of Ca²⁺, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating, hypercholesterolemia. Caused by mineralocorticoid activity - fluid retention and Na⁺(peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue). Epidural lipomatosis.

Disturbances from musculoskeletal and connective tissue: slowing growth and ossification processes in children (premature closure of epiphyseal growth zones),osteoporosis (very rare - pathological bone fractures, aseptic necrosis of the head of the humerus and thigh bone), rupture of the tendons of the muscles, steroid myopathy, decrease in muscle mass (atrophy).

Disturbances from the skin and mucous membranes: delayed healing of wounds, petechiae, ecchymosis, thinning of the skin, skin atrophy, telangiectasia, hypertrichosis, hyper- or hypopigmentation, "steroid" acne, steroid striae, propensity to develop pyoderma and candidiasis, rosace-like perioral dermatitis, suppression of reactions during skin tests .

Immune system disorders: generalized (skin rash, skin itching, anaphylactic shock) and local allergic reactions.

Disorders from the urinary system: leukocyturia.

Infectious and parasitic diseases: development or exacerbation of infections (the emergence of this side effect is facilitated by jointly used immunosuppressants and vaccination).

General disorders and disorders at the site of administration: withdrawal syndrome; burning, numbness, pain, paresthesia and infection 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).

Overdose:

Symptoms: increased blood pressure, edema (peripheral), peptic ulcer, hyperglycemia, impaired consciousness.

Treatment: symptomatic, there is no specific antidote.

Interaction:

Dexamethasone is pharmaceutically incompatible with other drugs (LS) - insoluble compounds can form. It is recommended to administer it separately from other drugs (iv bolus, or via another dropper, as a second solution). When a solution of dexamethasone is mixed with heparin, a precipitate forms.

Dexamethasone increases the toxicity of cardiac glycosides (because of the resulting hypokalemia, the risk of arrhythmias increases).

Accelerates the removal of acetylsalicylic acid, reduces the content of its metabolites in the blood (with the abolition of dexamethasone, the concentration of salicylates in the blood increases and the risk of side effects increases).

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

Increases the metabolism of isoniazid, mexiletine (especially in "fast acetylators"), which leads to a decrease in their concentrations in the blood plasma.

Increases the risk of hepatotoxic effects of paracetamol (induction of liver enzymes and the formation of a toxic metabolite of paracetamol).

Increases (with prolonged therapy) the content of folic acid.

Hypokalemia caused by dexamethasone may increase the severity and duration of muscle blockade against the background of muscle relaxants.

In high doses reduces the effect of growth hormone.

Dexamethasone reduces the effect of hypoglycemic J1C; enhances the anticoagulant effect of coumarin derivatives.

Weaken the influence of vitamin D on absorption of Ca²⁴ in the lumen of the intestine. Ergocalciferol and parathyroid hormone interfere with the development of osteopathy caused by dexamethasone.

Reduces the concentration of praziquantel in the blood.

Cyclosporine (inhibits metabolism) and ketoconazole (reduces clearance) increase toxicity.

Thiazide diuretics, carbonic anhydrase inhibitors, other glucocorticosteroids and amphotericin B increase the risk of hypokalemia, Na-containing drugs - edema and increased blood pressure.

Non-steroidal anti-inflammatory drugs (NSAIDs) and ethanol increase the risk of ulceration of the gastrointestinal mucosa and bleeding, in combination with NSAIDs for the treatment of arthritis, it is possible to reduce the dose of GCS due to the summation of the therapeutic effect. Indomethacin, displacing dexamethasone from association with albumin, increases the risk of developing its side effects.

Amphotericin B and carbonic anhydrase inhibitors increase the risk of osteoporosis.

The therapeutic effect of dexamethasone decreases under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of microsomal liver enzymes (an increase in metabolic rate).

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

The clearance of dexamethasone rises on the background of the use of drugs of thyroid hormones.

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

Estrogens (including oral estrogen-containing contraceptives) reduce the clearance of dexamethasone, lengthen T_1/2 and their therapeutic and toxic effects.

The emergence of hirsutism and acne is facilitated by the simultaneous use of other steroid hormone drugs - androgens, estrogens, anabolic, oral contraceptives.

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

The risk of developing cataracts increases when used against other SCS, antipsychotic drugs (neuroleptics), carbutamide and azathioprine.

Simultaneous appointment with m-holinoblokatorami (including antihistamines, tricyclic antidepressants), nitrates contributes to the development of increased intraocular pressure.

With simultaneous use with fluoroquinolones, the risk of tendonitis (predominantly Achilles tendon) increases in elderly patients and in patients with tendon diseases.

Anti-malarial drugs increase the side effects of glucocorticosteroids.

Chlorokhin, hydroxychloroquine, mefloquine in combination with dexamethasone may increase the risk of myopathy, cardiomyopathy.

ACE inhibitors, when used concomitantly with dexamethasone, sometimes alter the composition of peripheral blood.

Special instructions:

During treatment with the drug Dexamethasone (especially long) it is necessary to observe the oculist, monitor blood pressure and the state of water-electrolyte balance, as well as patterns of peripheral blood and blood glucose concentration.

In order to reduce side effects, antacids should be prescribed, as well as increased intake into the body of K⁺ (diet, preparations K⁺). 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 cirrhosis of the liver.

It should be noted that in patients with hypothyroidism, the clearance of dexamethasone decreases, and in patients with thyrotoxicosis - increases.

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

It should be carefully monitored by the patient within a year after the end of long-term therapy with the drug Dexamethasone in connection with the possible development of a relative insufficiency of the adrenal cortex in stressful situations. Long-term use of high doses of the drug requires a gradual dose reduction in order to prevent the development of acute adrenocortical insufficiency.

With the use of dexamethasone, there is a risk of developing severe anaphylactic reactions, bradycardia.

On the background of therapy with the drug, the risk of activation of strongyloidiasis is increased.

The dose of dexamethasone should be temporarily increased in case of stressful situations (surgical intervention, trauma). The dose of dexamethasone is recommended to be increased before the planned surgical intervention and to apply an increased dose of the drug during the early postoperative period.

Against the background of treatment with dexamethasone, it is necessary to use specific antibacterial therapy for the therapy of latent tuberculosis, lymphadenitis after BCG vaccination, poliomyelitis, acute and chronic bacterial, parasitic infections and specific therapy in patients with peptic ulcer and osteoporosis.

During therapy with the drug, careful monitoring of the condition of patients with chronic heart failure,uncontrolled arterial hypertension, trauma and ulcerative lesions of the cornea, glaucoma.

May worsen myasthenia flow.

With a sudden withdrawal of the drug Dexamethasone, especially in the case of prior application of high doses, the development of acute adrenal insufficiency is possible; withdrawal syndrome (not due to adrenal insufficiency): decreased appetite, nausea, vomiting, retardation, headache, generalized musculoskeletal pain, asthenia; as well as the aggravation of the disease, in connection with which the drug was prescribed Dexamethasone. therefore Dexamethasone it is necessary to cancel by gradual reduction of doses for the prevention of the development of acute adrenal insufficiency.

In patients with diabetes mellitus, the concentration of blood glucose should be monitored and if necessary, dosages of hypoglycemic drugs should be corrected.

A drug Dexamethasone may increase susceptibility or mask the symptoms of infectious diseases.

The drug may mask the symptoms of peritoneal irritation in patients with a perforation of the intestinal wall or stomach.

With the use of glucocorticosteroids, a change in the mobility and quantity of spermatozoa is possible.

Veterinary pox, measles and other infections can be more severe and even fatal in non-immune individuals. Immunosuppression often develops with prolonged use, but it can also occur with short-term treatment with a drug Dexamethasone.

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

At children during long treatment by a preparation Dexamethasone it is necessary to closely monitor the dynamics of growth and development.

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

During the treatment period, it is necessary to refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for injection, 4 mg / ml.

Packaging:

1 ml or 2 ml in a vial of dark glass.

5 ampoules per contour cell pack.

For 1, 2, 3, 4 or 5 contour squares (5, 10, 15, 20, 25 ampoules), together with the instructions for use and the scarifier are placed in a cardboard box.

At 5, 10, 15, 20, 25 ampoules in a cellular cardboard lattice, one lattice together with an instruction for use and a scarifier are placed in a cardboard pack.

When using ampoules with a dot or a ring of fracture, the ampoule scaper is not inserted.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003438

Date of registration:02.02.2016

Expiration Date:02.02.2021

The owner of the registration certificate:Jodas Expo Pvt.LtdJodas Expo Pvt.Ltd India

Manufacturer: & nbsp

JODAS EXPOIM, Pvt. Ltd. India

Representation: & nbspJodas Expoim, Open CompanyJodas Expoim, Open Company

Information update date: & nbsp21.03.2017

Illustrated instructions

Instructions

Dexamethasone (Dexamethasone)