Dexamethasone-Vial (Solution) Instructions for Use

Marketing Authorization Holder

Vial, LLC (Russia)

Manufactured By

CSPC Ouyi Pharmaceutical, Co. Ltd. (China)

Labeled By

OZON, LLC (Russia)

ATC Code

H02AB02 (Dexamethasone)

Active Substance

Dexamethasone (Rec.INN registered by WHO)

Dosage Form

Dexamethasone-Vial

Injection solution 4 mg/1 ml: amp. 5 or 10 pcs.

Dosage Form, Packaging, and Composition

1 ml – ampoules (10) – carton packs.
1 ml – ampoules (5) – contour plastic packs (1) – carton packs.
1 ml – ampoules (5) – contour plastic packs (2) – carton packs.
1 ml – dark glass ampoules (10) – carton boxes.
1 ml – dark glass ampoules (10) – carton packs.
1 ml – dark glass ampoules (5) – carton packs.
1 ml – dark glass ampoules (5) – contour plastic packs (1) – carton packs.
1 ml – dark glass ampoules (5) – contour plastic packs (2) – carton packs.

Clinical-Pharmacological Group

Injectable corticosteroids

Pharmacotherapeutic Group

Systemic corticosteroids; glucocorticoids

Pharmacological Action

Glucocorticosteroid (GCS) – a methylated derivative of fluprednisolone, inhibits the release of interleukin-1, interleukin-2, and interferon gamma from lymphocytes and macrophages. It has anti-inflammatory, anti-allergic, desensitizing, anti-shock, antitoxic, and immunosuppressive effects.

It suppresses the release of adrenocorticotropic hormone (ACTH) and beta-lipotropin by the pituitary gland but does not reduce the level of circulating beta-endorphin. It inhibits the secretion of thyroid-stimulating hormone (TSH) and follicle-stimulating hormone (FSH).

It increases the excitability of the central nervous system, reduces the number of lymphocytes and eosinophils, and increases the number of red blood cells (stimulates the production of erythropoietins).

It interacts with specific cytoplasmic receptors and forms a complex that penetrates the cell nucleus and stimulates the synthesis of mRNA; the latter induces the formation of proteins, including lipocortin, which mediate cellular effects. Lipocortin inhibits phospholipase A2, suppresses the release of arachidonic acid, and inhibits the synthesis of endoperoxides, prostaglandins, and leukotrienes, which contribute to inflammation and allergy processes.

Protein metabolism: reduces the amount of protein in 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 thyroglobulin (TG), redistributes fat (accumulation of fat mainly in 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 release of glucose from the liver into the blood; increases the activity of phosphoenolpyruvate carboxykinase and the synthesis of aminotransferases, leading to the activation of gluconeogenesis.

Water-electrolyte metabolism: retains sodium ions and water in the body, stimulates the excretion of potassium ions (mineralocorticosteroid activity), reduces the absorption of calcium ions from the gastrointestinal tract, “leaches” calcium ions from bones, increases the excretion of calcium ions by the kidneys.

The anti-inflammatory effect is associated with the inhibition of the release of inflammatory mediators by eosinophils; induction of lipocortin formation and a decrease in the number of mast cells producing hyaluronic acid; as well as with a decrease in capillary permeability; stabilization of cell membranes and organelle membranes (especially lysosomal).

The anti-allergic effect develops as a result of suppression of the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, a decrease in the number of circulating basophils, suppression of the development of lymphoid and connective tissue, a decrease in the number of T- and B-lymphocytes, mast cells, a decrease in the sensitivity of effector cells to allergy mediators, inhibition of antibody formation, and a change in the body’s immune response.

In chronic obstructive pulmonary diseases (COPD), the action is based mainly on the inhibition of inflammatory processes, inhibition of the development or prevention of mucosal edema, inhibition of eosinophilic infiltration of the bronchial epithelium submucosal layer, deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucosa. It increases the sensitivity of beta-adrenergic receptors of small and medium caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces mucus viscosity by inhibiting or reducing its production.

The anti-shock and antitoxic effect is associated with an increase in blood pressure (due to an increase in the concentration of circulating catecholamines and restoration of sensitivity to them of adrenergic receptors, as well as vasoconstriction), a decrease in vascular wall permeability, membrane-stabilizing properties, and activation of liver enzymes involved in the metabolism of endo- and xenobiotics.

The immunosuppressive effect is due to the inhibition of the release of cytokines (interleukin-1 and interleukin-2, interferon gamma) from lymphocytes and macrophages.

It suppresses the synthesis and secretion of ACTH and secondarily – the synthesis of endogenous GCS. It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

A feature of the action is significant inhibition of pituitary function and an almost complete absence of mineralocorticosteroid activity. Doses of 1-1.5 mg/day suppress the adrenal cortex; the biological half-life is 32-72 hours (duration of suppression of the hypothalamic-pituitary-adrenal system).

In terms of glucocorticoid activity, 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

After intramuscular injection, it is absorbed slowly, maximum plasma concentration is reached after 7-9 hours.

Plasma protein binding is 80%. It penetrates the blood-brain barrier and placental barrier.

It is metabolized in the liver. T_1/2 is 3-5 hours. It is excreted by the kidneys (a small part – by the lactating glands).

Indications

• Shock (burn, traumatic, surgical, toxic) when other therapy is ineffective;
• Allergic reactions (acute, severe forms), blood transfusion shock, anaphylactic shock, anaphylactoid reactions;
• Cerebral edema (including against the background of a brain tumor or associated with surgery, radiation therapy, or head injury);
• Bronchial asthma (severe form), status asthmaticus;
• Systemic connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis);
• Acute adrenal insufficiency;
• Thyrotoxic crisis;
• Acute hepatitis, hepatic coma;
• Poisoning with caustic fluids (reduction of inflammatory phenomena and prevention of cicatricial strictures).

ICD codes

Dosage Regimen

The dosage regimen is individual and depends on the indications, the patient’s condition, and their response to therapy. The drug is administered intravenously slowly as a bolus or by drip (in acute and emergency conditions); intramuscularly; local injection (into the pathological focus) is also possible. To prepare a solution for intravenous (IV) drip infusion, isotonic sodium chloride solution or 5% dextrose solution should be used.

Dexamethasone sodium phosphate: intra-articularly, into the lesion focus – 0.2-6 mg, repeated once every 3 days or 3 weeks.

IM or IV – 0.5-9 mg/day.

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

For treatment of shock – IV 20 mg in the first administration, then 3 mg/kg over 24 hours as IV infusions or IV bolus – from 2 to 6 mg/kg as a single injection or 40 mg as a single injection administered every 2-6 hours; IV administration of 1 mg/kg as a single dose is possible. Shock therapy should be discontinued as soon as the patient’s condition stabilizes, the usual duration is no more than 2-3 days.

Allergic diseases – IM in the first injection 4-8 mg. Further treatment is carried out with oral dosage forms.

For nausea and vomiting during chemotherapy – IV 8-20 mg 5-15 minutes before the chemotherapy session. Further chemotherapy should be carried out using oral dosage forms.

For treatment of neonatal respiratory distress syndrome – IM 4 injections of 5 mg every 12 hours, then from the seventh day once every 24 hours. Maximum daily dose is 80 mg.

For children: for the treatment of adrenal insufficiency – IM 23 mcg/kg (0.67 mg/m²) once every 3 days, or 7.8-12 mcg/kg (0.23-0.34 mg/m²/day), or 28-170 mcg/kg (0.83-5 mg/m²) every 12-24 hours.

Adverse Reactions

The frequency and severity of side effects depend on the duration of use, the dose used, and the possibility of observing the circadian rhythm of administration.

From the endocrine system: decreased glucose tolerance, “steroid” diabetes mellitus or manifestation of latent diabetes mellitus, suppression of adrenal function, Itsenko-Cushing syndrome (moon face, pituitary-type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia, striae), delayed sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, “steroid” gastric and duodenal ulcer, erosive esophagitis, gastrointestinal bleeding and perforation, increased or decreased appetite, 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 severity of chronic heart failure, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction – spread of the necrosis focus, slowing of scar tissue formation, 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, cerebellar pseudotumor, headache, convulsions.

From the sensory organs: sudden loss of vision (with parenteral administration in the head, neck, nasal conchae, scalp, deposition of drug crystals in the eye vessels is possible), posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, tendency to develop secondary bacterial, fungal or viral eye infections, trophic changes in the cornea, exophthalmos.

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

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

From the musculoskeletal system: slowing of growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rarely – pathological bone fractures, aseptic necrosis of the humeral and femoral head), muscle tendon rupture, “steroid” myopathy, decrease in muscle mass (atrophy).

From the skin and mucous membranes: delayed wound healing, petechiae, ecchymoses, skin thinning, hyper- or hypopigmentation, steroid acne, striae, tendency to develop pyoderma and candidiasis.

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

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

Local with parenteral administration: burning, numbness, pain, paresthesia and infections at the injection site, rarely – necrosis of surrounding tissues, scar formation at the injection site; atrophy of the skin and subcutaneous tissue with IM injection (especially dangerous when injected into the deltoid muscle).

With IV administration: arrhythmias, “flushing” of the face, convulsions.

With intracranial administration – nosebleed.

With intra-articular administration – increased joint pain.

Contraindications

• For short-term use for “vital” indications, the only contraindication is hypersensitivity.

For intra-articular administration: previous arthroplasty, pathological bleeding (endogenous or caused by the use of anticoagulants), intra-articular bone fracture, infectious (septic) inflammatory process in the joint and periarticular infections (including in history), as well as a general infectious disease, severe periarticular osteoporosis, absence of signs of inflammation in the joint (so-called “dry” joint, for example, in osteoarthritis without synovitis), severe bone destruction and joint deformity (sharp narrowing of the joint space, ankylosis), joint instability as an outcome of arthritis, aseptic necrosis of the bone epiphyses forming the joint.

With caution

• Parasitic and infectious diseases of viral, fungal or bacterial nature (current or recently suffered, including recent contact with a patient) – herpes simplex, herpes zoster (viremic phase), chickenpox, measles; amoebiasis, strongyloidiasis (established or suspected) systemic mycosis; active and latent tuberculosis. 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 states (including AIDS or HIV infection);
• Gastrointestinal diseases: gastric and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, recently created intestinal anastomosis, ulcerative colitis with threat of perforation or abscess formation, diverticulitis;
• Cardiovascular diseases, including recently suffered myocardial infarction (in patients with acute and subacute myocardial infarction, spread of the necrosis focus, slowing of scar tissue formation and, as a result, rupture of the heart muscle is possible), decompensated chronic heart failure, arterial hypertension, hyperlipidemia;
• Endocrine diseases – diabetes mellitus (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itsenko-Cushing’s disease;
• Severe chronic renal and/or hepatic failure, nephrourolithiasis;
• Hypoalbuminemia and conditions predisposing to its occurrence;
• Systemic osteoporosis, myasthenia gravis, acute psychosis, obesity (III-IV degree), poliomyelitis (except for the form of bulbar encephalitis), open-angle and closed-angle glaucoma.

For intra-articular administration: the patient’s general severe condition, ineffectiveness (or short duration) of the action of 2 previous injections (taking into account the individual properties of the glucocorticosteroids used).

Use in Pregnancy and Lactation

During pregnancy (especially in the first trimester), the drug can be used only when the expected therapeutic effect outweighs the potential risk to the fetus. During long-term therapy in pregnancy, the possibility of impaired fetal growth cannot be ruled out. If used at the end of pregnancy, there is a danger of atrophy of the fetal adrenal cortex, 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.

Use in Hepatic Impairment

Use with caution in severe chronic liver failure.

Use in Renal Impairment

Use with caution in severe chronic renal failure.

Pediatric Use

Children who have been in contact with patients with measles or chickenpox during treatment with the drug are prophylactically prescribed specific immunoglobulins. Glucocorticosteroids should be used in children during the growth period only for absolute indications and under the especially careful supervision of the attending physician.

Special Precautions

Children who have been in contact with patients with measles or chickenpox during treatment are prophylactically prescribed specific immunoglobulins. Glucocorticosteroids should be used in children during the growth period only for absolute indications and under the especially careful supervision of the attending physician.

It must be taken into account that in patients with hypothyroidism, the clearance of glucocorticosteroids decreases, and in patients with thyrotoxicosis, it increases.

Overdose

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

Treatment: symptomatic, there is no specific antidote.

Drug Interactions

Dexamethasone is pharmaceutically incompatible with other medicinal products (it may form insoluble compounds).

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

It accelerates the excretion of acetylsalicylic acid and reduces the content of its metabolites in the blood (when dexamethasone is discontinued, the concentration of salicylates in the blood increases and the risk of side effects increases).

When used concomitantly with live antiviral vaccines and against the background of other types of immunization, it increases the risk of virus activation and the development of infections.

It increases the metabolism of isoniazid and mexiletine (especially in “fast acetylators”), which leads to a decrease in their plasma concentrations.

It increases the risk of hepatotoxic action of paracetamol (induction of “hepatic” enzymes and formation of a toxic metabolite of paracetamol).

It increases (with long-term therapy) the folic acid content.

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

In high doses, it reduces the effect of somatropin.

Dexamethasone reduces the action of hypoglycemic medicinal products; enhances the anticoagulant effect of coumarin derivatives.

It weakens the effect of vitamin D on the absorption of calcium ions in the intestinal lumen.

Ergocalciferol and parathyroid hormone prevent the development of osteopathy caused by glucocorticosteroids.

It 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; sodium-containing medicinal products increase the risk of edema and increased blood pressure.

NSAIDs and ethanol increase the risk of ulceration of the gastrointestinal mucosa and bleeding; in combination with NSAIDs for the treatment of arthritis, a reduction in the dose of glucocorticosteroids is possible due to the summation of the therapeutic effect.

Indomethacin, displacing Dexamethasone from binding with albumins, increases the risk of its side effects.

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

The therapeutic effect of glucocorticosteroids is reduced under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of “hepatic” microsomal enzymes (increased metabolic rate).

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

The clearance of glucocorticosteroids increases against the background of thyroid hormones.

Immunosuppressants increase the risk of infections and lymphoma or other lymphoproliferative disorders associated with the Epstein-Barr virus.

Estrogens (including oral estrogen-containing contraceptives) reduce the clearance of glucocorticosteroids, prolong their half-life and their therapeutic and toxic effects.

The appearance of hirsutism and acne is facilitated by the simultaneous use of other steroid hormonal medicinal products – androgens, estrogens, anabolic agents, oral contraceptives.

Tricyclic antidepressants may increase the severity of depression caused by the use of glucocorticosteroids (they are not indicated for the treatment of these side effects).

The risk of developing cataracts increases when used against the background of other glucocorticosteroids, antipsychotic medicinal products (neuroleptics), carbobutamide and azathioprine.

Concomitant administration with m-cholinolytics (including antihistamine medicinal products, tricyclic antidepressants) and nitrates contributes to the development of increased intraocular pressure.

With simultaneous intrathecal use with iofendylate, the risk of arachnoiditis increases.

Storage Conditions

Store in a light-protected place at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.