Dexamed - instructions for use, doses, side effects, contraindications

*Active substance:*
dexamethasone sodium phosphate, which	4.75 mg
is equivalent to dexamethasone phosphate	4.00 mg
*Excipients:*
sodium phosphate disubstituted dodecahydrate	12.60 mg
methylparahydroxybenzoate	1.80 mg
propyl parahydroxybenzoate	0.20 mg
sodium metabisulphite	1.00 mg
sodium chloride	2.00 mg
sodium citrate dihydrate	2.28 mg
disodium edetate	1.00 mg
water for injections	up to 1.0 ml

Description:Transparent, colorless or slightly yellowish 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 (GCS) - methylated derivative of fluoride prednisolone. Has anti-inflammatory, antiallergic, desensitizing, immunosuppressive, anti-shock and antitoxic action, increases the sensitivity of beta-adrenoreceptors to endogenous catecholamines.

Interacts with specific cytoplasmic receptors (receptors for GCS are present in all tissues, especially in the liver), with the formation of a complex inducing the formation of proteins (including enzymes that regulate vital processes in cells).

Protein metabolism: reduces the number of globulins in the plasma, increases the synthesis of albumins in the liver and kidneys (with an increase in the albumin / globulin ratio); reduces synthesis and enhances protein catabolism in muscle tissue.

Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (mobilization from the subcutaneous tissue of the extremities and accumulation of fat mainly in the region 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 (increased intake of glucose from the liver into the blood); increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases (activation of gluconeogenesis); promotes the development of hyperglycemia.

Water-electrolyte exchange: delays Na⁺ and water in the body, stimulates the excretion of K⁺(mineralocorticoid activity), reduces the absorption of Ca²⁺ from the gastrointestinal tract, causing "washout" of calcium from the bones and increase its renal excretion, reduces bone mineralization.

Anti-inflammatory effect is associated with the suppression of the release of eosinophils and mast cells 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 (especially lysosomal) and membranes of organelles. It works on all stages of the inflammatory process: it inhibits the synthesis of prostaglandins (Pg) at the level of arachidonic acid (lipocortin oppresses phospholipase A₂Suppresses liberatiou arachidonic acid and endoperekisey inhibits the biosynthesis of the leukotrienes contribute to inflammation, allergies, etc.), synthesis of "proinflammatory cytokine" (interleukin-1, tumor necrosis factor alpha, etc.)..; increases the resistance of the cell membrane to the action of various damaging factors.

Immunodepressive effect caused by the involution of lymphoid tissue,inhibition of the proliferation of lymphocytes (especially T-lymphocytes), suppression of B-cell migration and interaction of T and B lymphocytes, inhibition of the release of cytokines (interleukin-1, 2, gamma-interferon) from lymphocytes and macrophages and a decrease in the formation of antibodies.

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

In obstructive airway diseases, the effect is mainly due to the inhibition of inflammatory processes, the prevention or reduction of the degree of edema of the mucous membranes, the decrease in the eosinophilic infiltration of the submucosal layer of the bronchial epithelium and the deposition of circulating immune complexes in the bronchial mucosa, as well as the 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 by reducing its production. It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

Suppresses the synthesis and secretion of ACTH and, again, the synthesis of endogenous GCS.

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).

By the force of glucocorticoid activity 0.5 mg dexamethasone correspond to about 3.5 mg of prednisone (or prednisolone), 15 mg of hydrocortisone or cortisone 17.5 mg.

Pharmacokinetics:

Blood is bound (60-70%) with a specific transporter protein - transcortin. Easily passes through the histohematological barriers (including through blood-brain and placental). Metabolised in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites. It is excreted by the kidneys (a small part by the lactating glands).The half-life of dexamethasone from the plasma is 3-5 hours.

Indications:

Diseases requiring the introduction of a fast-acting glucocorticosteroid, as well as cases where oral administration of the drug is not possible:

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

- 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, 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 suffering from malignant tumors, with the impossibility of oral treatment;

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

- severe infectious diseases (in combination with antibiotics);

- in ophthalmic practice (subconjunctival, retrobulbar or parabulbar injection): allergic conjunctivitis, keratitis, keratoconjunctivitis without epithelial damage, irit, 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.

Contraindications:

The only contraindication for short-term use for life indications is hypersensitivity to dexamethasone or the components of the drug.

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

Carefully:

With the following diseases and conditions:

- Diseases of the gastrointestinal tract - gastric ulcer and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with perforation or abscessing threat, diverticulitis.

- Parasitic and infectious diseases of viral, fungal or bacterial nature (currently occurring or recently transferred, including recent contact with the patient) - herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amebiasis, strongyloidiasis; systemic mycosis; active and latent tuberculosis. The 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, incl. recently suffered myocardial infarction (in patients with acute and subacute myocardial infarction it is possible to spread a foci of necrosis,slowing the formation of scar tissue and as a result - rupture of the heart muscle), severe chronic heart failure, hypertension, hyperlipidemia.

- Endocrine diseases - diabetes (including a violation of carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease, obesity (III-IV c).

- Severe chronic renal and / or hepatic insufficiency, nephrourolythiasis.

- Hypoalbuminemia and conditions predisposing to its occurrence (cirrhosis of the liver, nephrotic syndrome).

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

- Pregnancy.

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:

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

The drug is administered intravenously slowly by jet or drip (in acute and urgent conditions); intramuscularly; possibly also local (in pathological education) introduction.

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

In an acute period with various diseases and at the beginning of therapy, Dexamed® is used in higher doses. Within a day, you can inject 4 to 20 mg of Dexamed ® 3-4 times.

Doses of the drug for children (intramuscularly):

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. With other indications, the recommended dose is from 0.02776 to 0.1666 mg / kg body weight or 0.833 to 5 mg / m²body surface area every 12-24 hours.

When the effect is achieved, the dose is reduced to a maintenance dose or until the treatment is discontinued. The duration of parenteral use is usually 3-4 days, then switch to maintenance therapy with dexamethasone in tablets.

Long-term use of high doses of the drug requires a gradual dose reduction in order to prevent the development of acute adrenocortical insufficiency.

Side effects:

Usually Dexamed® is well tolerated. It has a low mineralocorticoid activity, i.e. its effect on water-electrolyte exchange is small. As a rule, low and medium doses of Dexamed® do not cause delays in sodium and water in the body, increased excretion of potassium.

The following side effects are described:

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, muscle weakness, striae), delay in sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, digestive disorders, flatulence, hiccups. In rare cases - increased activity of "liver" transaminases and alkaline phosphatase

From the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased heart failure, 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, cerebral palsy, headache, convulsions.

From the sense organs: sudden loss of vision (with parenteral administration in the head, neck,turbinate, the scalp may be deposited drug crystals in the blood vessels of the eye), posterior subcapsular cataracts, increased intraocular pressure with possible damage to the optic nerve, the propensity to develop secondary bacterial, fungal or viral infections of the eyes, corneal trophic changes, exophthalmos.

From the side of metabolism: increased calcium excretion, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

Due to mineralocorticoid activity - fluid retention and sodium (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

From the musculoskeletal system: slowing growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rare - pathological fractures, aseptic necrosis of the humeral head and femur), rupture of tendons of muscles, steroid myopathy, loss of muscle mass (atrophy).

From the skin and mucous membranes: delayed healing of wounds, petechiae, ecchymosis, thinning of the skin, hyper or hypopigmentation, acne, striae, a tendency to develop pyoderma and candidiasis.

Allergic reactions: generalized (skin rash, itching, anaphylactic shock), local allergic reactions.

Local: burning, numbness, pain, tingling, flushing 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: development or exacerbation of infections (the appearance of this side effect is facilitated by jointly used immunosuppressants and vaccination), leukocyturia. withdrawal syndrome.

With IV introduction: arrhythmias, "tides" of blood to the face, seizures.

Overdose:

It is possible to strengthen the above described side effects. It is necessary to reduce the dose of Dexamed ®. Treatment is symptomatic.

Interaction:

The pharmaceutical incompatibility of Dexamed ® with other intravenously administered drugs is possible - it is recommended to administer it separately from other drugs (iv bolus, or via another drip as a second solution).When a solution of dexamethasone is mixed with heparin, a precipitate forms.

Simultaneous administration of Dexamed® with:

- inducers of "hepatic" microsomal enzymes (phenobarbital, rifampicin, phenytoin, theophylline, ephedrine) leads to a decrease in its concentration;

- Diuretics (especially "thiazide" and inhibitors of carbonic anhydrase) and amphotericin B can lead to increased excretion of K⁺;

- with sodium-containing drugs - development of edema and increased blood pressure;

- amphotericin B - the risk of developing heart failure increases;

- cardiac glycosides - their tolerance is worsened and the likelihood of developing ventricular extrasystole (due to induced hypokalemia) increases;

- indirect anticoagulants weakens (less intensifies) their effect (dose adjustment required);

- anticoagulants and thrombolytics - Increased risk of bleeding from ulcers in the gastrointestinal tract;

- ethanol and non-steroidal anti-inflammatory drugs (NSAIDs) - the risk of erosive and ulcerative lesions in the gastrointestinal tract and the development of bleeding (in combination with NSAIDs in the treatment of arthritisit is possible to reduce the dose of glucocorticosteroids due to the summation of the therapeutic effect);

- paracetamol - The risk of hepatotoxicity increases (induction of hepatic enzymes and the formation of a toxic metabolite of paracetamol);

- acetylsalicylic acid - accelerates its excretion and reduces the concentration in the blood (with the dexamethasone withdrawal, the level of salicylates in the blood increases and the risk of side effects increases);

- insulin and oral hypoglycemic drugs, antihypertensive drugs - their effectiveness is reduced;

- vitamin D - its effect on the absorption of Ca decreases²⁺ in the intestine;

- Growth hormone - reduces the effectiveness of the latter, and with praziquantel - him concentration;

- M-holinoblokatorami (including antihistamines and tricyclic antidepressants) and nitrates - promotes increased intraocular pressure;

- isoniazid and mexelitin - increases their metabolism (especially in "slow" acetylators), which leads to a decrease in their plasma concentrations.

Carboangidrase inhibitors and looped diuretics may increase the risk of osteoporosis.

Indomethacin, displacing Dexamed® from its association with albumin, increases the risk of developing its side effects.

ACTH enhances the action of Dexamed®.

Ergocalciferol and parathyroid hormone interfere with the development of osteopathy caused by Dexamed®.

Cyclosporine and ketoconazole, slowing the metabolism of Dexamed®, can in some cases increase its toxicity.

Simultaneous appointment androgen and steroid anabolic drugs with Dexamed® contributes to the development of peripheral edema and hirsutism, the appearance of acne.

Estrogens and oral estrogen-containing contraceptives reduce the clearance of Dexamed ®, which can be accompanied by an increase in the severity of its action.

Mitotan and other inhibitors of adrenal cortex function may necessitate increasing the dose of Dexamed®.

With simultaneous application with living antiviral vaccines and against other types of immunization increases the risk of virus activation and the development of infections.

Antipsychotic drugs (antipsychotics) and azathioprine increase the risk of developing cataracts when prescribing Dexamed®.

With simultaneous application with antithyroid drugs It decreases, and with thyroid hormones - the clearance of Dexamed ® increases.

Special instructions:

Before the beginning of treatment (if it is impossible due to the urgency of the condition - during the 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 formula of blood, the content of glucose and electrolytes in the blood plasma.

During treatment with Dexamed ® (especially long-term) it is necessary to observe the oculist, control blood pressure and condition of the water-electrolyte balance, as well as pictures of peripheral blood and blood glucose level.

In order to reduce side effects, it is necessary to increase the intake of K⁺ in the body (diet, potassium preparations). 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 hypothyroidism and liver cirrhosis.

The drug may enhance existing emotional instability or psychotic disorders.When referring to psychoses in an anamnesis, Dexamed® in high doses is prescribed under the strict supervision of a physician.

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 connection with an increase in the need for glucocorticosteroids. Patients should be monitored carefully within a year after the end of prolonged therapy with Dexamed ®, in connection with the possible development of relative insufficiency of the adrenal cortex in stressful situations.

In case of sudden cancellation, especially in case of prior application of high doses, it is possible to develop the "withdrawal" syndrome (anorexia, nausea, block, generalized musculoskeletal pain, general weakness), as well as exacerbation of the disease that Dexamed® was assigned to.

During treatment with Dexamed®, vaccination should not be given due to a decrease in its effectiveness (immune response).

When prescribing Dexamed® for intercurrent infections, septic states and tuberculosis, it is necessary to simultaneously perform antibiotic treatment with bactericidal action.

Children during prolonged treatment with Dexamed ® 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.

Patients with diabetes should monitor blood glucose and, if necessary, correct therapy.

An x-ray control of the osteoarticular system (images of the spine, hands) is shown.

In patients with latent infectious diseases of the kidneys and urinary tracts, Dexamed® can cause leukocyturia, which can be of diagnostic significance.

Dexamed® increases the metabolites content of 11- and 17-oxyketocorticosteroids.

Form release / dosage:Solution for intravenous and intramuscular injection, 4 mg / ml.

Packaging:

By 1.0 ml or 2.0 ml into dark glass ampoules (class I).

5 ampoules per contour mesh package made of PVC film with PVC coating.

2 contour squares, together with instructions for use, are placed in a cardboard box.

For 20 contour packs with instructions for use in cardboard pack.

Storage conditions:

In a dry place, protected from light and out of reach of children, at a temperature not exceeding 25 ° C.

Shelf life:

3 of the year.

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

Terms of leave from pharmacies:On prescription

Registration number:P N 015488/01

Date of registration:15.12.2008 / 11.09.2012

Expiration Date:Unlimited

The owner of the registration certificate:Medocemi Co., Ltd.Medocemi Co., Ltd. Cyprus

Manufacturer: & nbsp

MEDOCHEMIE, Ltd. Cyprus

Representation: & nbspMEDOKEMI LTD. MEDOKEMI LTD. Cyprus

Information update date: & nbsp20.03.2017

Illustrated instructions

Instructions

Dexamed® (Dexamed®)