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

Excipients: methylparahydroxybenzoate 1.5 mg, propyl parahydroxybenzoate 0.2 mg, sodium disulfite 1.0 mg, sodium citrate aqueous 10.0 mg, propylene glycol 50.0 mg, sodium hydroxide (q.s. up to pH 7.0-8.5), water for injection up to 1 ml.

Description:Transparent, colorless or slightly yellowish solution.

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:

Glucocorticosteroid (GCS) is 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 penetrating into the nucleus cells and stimulating 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 activation of gluconeogenesis.

Water-electrolyte exchange: delays 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,inhibition 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 (by increasing the concentration of circulating catecholamines and restoring 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 is caused by inhibition of the release of cytokines (interleukin-1 and interleukin-2, gamma-interferon) from lymphocytes and macrophages.

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.

Doses of 1-1.5 mg / day inhibit the adrenal cortex; biological half-life (T_1/2) - 32-72 h (the duration of oppression of the hypothalamic-pituitary-adrenal system).

Pharmacokinetics:

After intramuscular injection is absorbed slowly, the maximum concentration in the plasma is achieved after 7-9 hours. Communication with plasma proteins - 80%. Penetrates through the blood-brain barrier and placental barrier. Metabolised in the liver. T_1/2- 3-5 hours.It is excreted by the kidneys (a small part by the lactating glands).

Indications:

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

- 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 in patients 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): allergic conjunctivitis, keratitis, keratoconjunctivitis without epithelial damage, irit, iridocyclitis, blepharitis, blepharoconjunctivitis, scleritis, episcleritis, inflammation after eye injuries and surgical interventions, sympathetic ophthalmia, immunosuppressive treatment after transplantation cornea;

- 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 according to "vital" indications, the only contraindication is hypersensitivity to the components of the drug.

Carefully:

With the following diseases and conditions:

Systemic parasitic and infectious diseases of viral, fungal or bacterial nature (currently or recently transferred, including recent contact with the patient) - herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amoebiasis, strongyloidiasis (or suspected); systemic mycosis; 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.

Diseases of the cardiovascular system (CVS),including a recently transferred myocardial infarction (in patients with acute and subacute myocardial infarction, a necrosis focus, a delay in the formation of scar tissue and, as a consequence, a rupture of the heart muscle), 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 and / or hepatic insufficiency, nephrourolythiasis.

Hypoalbuminemia and conditions predisposing to its occurrence.

Liver failure.

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

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

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

Pregnancy.

In children during growth Dexamethasone It should be used only under absolute indications and under very careful supervision of the attending physician.

Pregnancy and lactation:

During pregnancy (especially in the first trimester) the drug can be applied only when the expected therapeutic effect for the mother 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, breast-feeding 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 (iv) slowly struino or drip (with acute and urgent conditions); intramuscularly (intramuscularly); possibly also local (in pathological education) introduction. In order to prepare a solution for intravenous infusion, an isotonic solution of sodium chloride or a 5% solution of dextrose should be used.

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. With other indications, the recommended dose is from 0.02776 to 0.1666 mg / kg body weight or 0.833 to 5 mg / m² body surface area every 12-24 hours.

Long-term use of high doses of the drug requires a gradual dose reduction in order to prevent the development of acuteinsufficiency of the adrenal cortex.

Side effects:The frequency of development and severity of side effects depend on duration of application, the amount of dose used, and the possibility of observing the circadian rhythm of the appointment.

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.

From the digestive system: nausea, vomiting, pancreatitis, "steroid" stomach ulcers and 12 duodenal ulcer, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, flatulence, hiccups. In rare cases - increased activity of "liver" transaminases and alkaline phosphatase.

From the CAS side: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of CHF, changes in the electrocardiogram, 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, nasal concha, scalp may precipitate crystals of the drug in the vessels of the eye), posterior subcapsular cataracts, increased intraocular pressure with possible damage to the optic nerve, propensity to develop secondary bacterial, fungal or viral infections eye, trophic changes of the cornea, exophthalmos.

From the side of metabolism: increased excretion of Ca²⁺, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

Caused by mineralocorticoid activity - fluid retention and Na⁺ (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

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

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

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

Other: development or exacerbation of infections (the emergence of this side effect is facilitated by jointly used immunosuppressants and vaccination), leukocyturia, withdrawal syndrome.

Local for parenteral administration: 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).

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

Overdose:

It is possible to strengthen the above described dose-dependent side effects. It is necessary to reduce the dose of Dexamethasone. Treatment is symptomatic.

Interaction:

Dexamethasone is pharmaceutically incompatible with other drugs (LS) (can form insoluble compounds). It is recommended to inject it separately from other drugs (iv bolus, or through 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 use with live antiviral vaccines and against other types of immunizations, increases the risk of virus activation and the development of infections.

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

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

Weaken the influence of vitamin D on absorption of Ca²⁺ 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 its 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.

Special instructions:

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

In order to reduce side effects, it is necessary to increase the intake 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 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 prolonged therapy with Dexamethasone in connection with the possible development of a relative insufficiency of the adrenal cortex in stressful situations.

With the sudden withdrawal of Dexamethasone, especially in the case of prior application of high doses, the development of acute adrenal insufficiency is possible; withdrawal syndrome (not caused by adrenal insufficiency): decreased appetite, nausea, vomiting, retardation, headache, generalized musculoskeletal pain, asthenia; as well as exacerbation of the disease, which was appointed Dexamethasone.

Patients with diabetes should monitor blood glucose and, if necessary, adjust dosages of hypoglycemic drugs.

Children who were in contact with sick measles or chickenpox during the treatment period prophylactically prescribe specific immunoglobulins. Children during long-term treatment with Dexamethasone need careful monitoring of the dynamics of growth and development.

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

During the period of treatment it is necessary to refrain from driving motor 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:

For pharmacies:

For 1 or 2ml of the drug in a vial of dark glass with a dot or ring fracture.

For 2 ml of the drug in a bottle of dark glass, ukuporenny rubber stopper, obkatannoy aluminum cap.

For 5 ampoules or vials in the contour mesh packaging / pallet.

1, 2, 3, 4 or 5 contour mesh packages / pallets (5, 10, 15, 20, 25 ampoules or vials) are placed together with the instructions for use in a cardboard pack.

For hospitals:

For 1 or 2 ml of the drug in a vial of dark glass with a dot or kink ring.

For 2 ml of the drug in a bottle of dark glass, ukuporenny rubber stopper, obkatannoy aluminum cap.

5 ampoules or bottles are placed in a contour mesh package / pallet.

2, 4, 8, 20, 40, 60 contour squares / pallets (10, 20, 40, 100, 200, 300 ampoules or vials) together with an equal number of instructions for use in the cardboard box.

Storage conditions:

In a dry place, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001018

Date of registration:18.10.2011 / 11.03.2016

Expiration Date:18.10.2016

The owner of the registration certificate:S.P.Inkomed Pvt.LtdS.P.Inkomed Pvt.Ltd India

Manufacturer: & nbsp

S.P.INCOMED, Pvt.Ltd. India

Representation: & nbspSP.INKOMED LLCSP.INKOMED LLC

Information update date: & nbsp20.03.2017

Illustrated instructions

Instructions

Dexamethasone (Dexamethasone)