Dexamethasone

INSTRUCTION for medical use of the medicinal product DEXAMETHASONE (DEXAMETHASONE)

Composition:

Active substance: dexamethasone;

1 tablet contains 0.5 mg of dexamethasone;

Excipients: lactose monohydrate, pregelatinized starch, magnesium stearate, colloidal anhydrous silicon dioxide.

Pharmaceutical form. Tablets.

Main physico-chemical properties: round, white or almost white tablets with bevelled edges.

Pharmacotherapeutic group. Systemic corticosteroids, glucocorticoids.

ATC code H02AB02.

Pharmacological properties.

Pharmacodynamics.

Dexamethasone is a synthetic adrenocortical hormone (a corticosteroid) with glucocorticoid activity. It exerts anti-inflammatory and immunosuppressive effects and also affects energy metabolism, glucose metabolism, and (via negative feedback) the secretion of hypothalamic corticotropin-releasing factor and adenohypophyseal tropic hormones.

The mechanism of action of glucocorticoids is not yet fully understood. Currently, there is sufficient evidence supporting the mechanism of glucocorticoid action at the cellular level. Two well-defined receptor systems exist in the cytoplasm of cells. By binding to glucocorticoid receptors, corticosteroids exert anti-inflammatory and immunosuppressive effects and regulate glucose metabolism. By binding to mineralocorticoid receptors, they regulate sodium and potassium metabolism and water-electrolyte balance.

Glucocorticoids are lipid-soluble and readily penetrate target cells through the cell membrane. Hormone binding to the receptor induces a conformational change in the receptor, increasing its affinity for DNA. The hormone-receptor complex enters the cell nucleus and binds to a regulatory site on the DNA molecule, known as the glucocorticoid response element (GRE). The activated receptor, bound to the GRE or specific genes, regulates mRNA transcription, which may be either increased or decreased. The newly formed mRNA is transported to the ribosomes, leading to the synthesis of new proteins. Depending on the target cells and cellular processes, protein synthesis may be enhanced (e.g., tyrosine transaminase production in liver cells) or suppressed (e.g., IL-2 production in lymphocytes). Since glucocorticoid receptors are present in all tissue types, it can be assumed that glucocorticoids affect most cells in the body.

Effects on energy metabolism and glucose homeostasis

Dexamethasone, together with insulin, glucagon, and catecholamines, regulates energy storage and utilization. In the liver, it increases glucose formation from pyruvates or amino acids and promotes glycogen synthesis. In peripheral tissues, especially in muscles, glucose uptake is reduced, and amino acids are mobilized (from proteins), serving as substrates for hepatic gluconeogenesis. The direct effect on fat metabolism includes central redistribution of adipose tissue and enhanced lipolytic response to catecholamines.

Via receptors in the renal proximal tubules, dexamethasone increases renal blood flow and glomerular filtration, inhibits vasopressin synthesis and secretion, and enhances the kidney's ability to excrete acids.

By increasing the number and affinity of β-adrenergic receptors, which mediate the positive inotropic effect of catecholamines, dexamethasone directly enhances myocardial contractility and peripheral vascular tone.

When administered in high doses, dexamethasone inhibits fibroblast production of types I and III collagen and synthesis of glycosaminoglycans. Thus, by suppressing extracellular collagen and matrix formation, wound healing is delayed. Prolonged administration in high doses leads to progressive bone resorption via indirect effects and reduced osteogenesis via direct effects (increased parathyroid hormone secretion and decreased calcitonin secretion), resulting in a negative calcium balance due to reduced intestinal calcium absorption and increased urinary calcium excretion. This typically leads to secondary hyperparathyroidism and phosphaturia.

Effects on the pituitary and hypothalamus

Dexamethasone is approximately 30 times more potent than cortisol. Therefore, it is a more powerful inhibitor of corticotropin-releasing factor (CRF) and pituitary adrenocorticotropic hormone (ACTH) secretion compared to endogenous cortisol. This leads to reduced cortisol secretion and, after prolonged suppression of CRF and ACTH secretion, to adrenal gland atrophy. Adrenal insufficiency may develop as early as 5–7 days after initiating dexamethasone at a dose equivalent to 20–30 mg of prednisone per day, or after 30 days of low-dose therapy. After discontinuation of short-term therapy (up to 5 days) with high doses, adrenal function should recover within one week; after prolonged therapy, normalization takes longer, usually up to one year. In some patients, irreversible adrenal atrophy may develop.

Anti-inflammatory and immunosuppressive effects of glucocorticoids are based on their molecular and biochemical actions. The molecular anti-inflammatory effect results from binding to glucocorticoid receptors and altering the expression of several genes that regulate the formation of various signaling molecules, proteins, and enzymes involved in the inflammatory response. The biochemical anti-inflammatory action of glucocorticoids results from blocking the production and function of humoral mediators of inflammation: prostaglandins, thromboxanes, cytokines, and leukotrienes. Dexamethasone reduces leukotriene formation by inhibiting the release of arachidonic acid from cellular phospholipids via inhibition of phospholipase A2 activity. The effect on phospholipase A2 is not due to direct action but results from increased concentration of lipocortin (macrocortin), an inhibitor of phospholipase A2. Dexamethasone inhibits prostaglandin and thromboxane synthesis by reducing the formation of specific mRNA, and consequently, the amount of cyclooxygenase produced. Dexamethasone also reduces platelet-activating factor (PAF) production by increasing lipocortin concentration. Other biochemical anti-inflammatory effects include reduced production of tumor necrosis factor (TNF) and interleukin-1 (IL-1).

Pharmacokinetics.

Dexamethasone is rapidly and almost completely absorbed after oral administration. The bioavailability of dexamethasone in tablets is approximately 80% (literature sources report bioavailability ranging from 53 to 112%). Maximum plasma concentration is reached within 1–2 hours after oral administration, and the duration of effect after a single dose is approximately 2.75 days.

Approximately 77% of dexamethasone in plasma is protein-bound, primarily to albumin. Only a small amount binds to other proteins. Dexamethasone is lipophilic and thus freely penetrates cells and interstitial spaces. In the central nervous system (hypothalamus, pituitary), it binds to and acts via membrane receptors. In peripheral tissues, it binds and acts via cytoplasmic receptors. Its degradation occurs at the site of action, i.e., within the cell itself. Dexamethasone is primarily metabolized in the liver, and possibly also in the kidneys and other tissues. It is predominantly excreted in urine.

Clinical Characteristics.

Indications.

Endocrine disorders:

• Replacement therapy for primary or secondary (pituitary) adrenal insufficiency (except acute adrenal insufficiency, where hydrocortisone or cortisone are the drugs of choice due to their more pronounced hormonal effect); congenital adrenal hyperplasia; thyroiditis, subacute form and severe forms of radiation thyroiditis.

Rheumatic diseases:

• Rheumatoid arthritis, including juvenile rheumatoid arthritis and extra-articular manifestations of rheumatoid arthritis (rheumatoid lungs, cardiac and ocular involvement, cutaneous vasculitis), as adjunctive therapy during the period when basic therapy has not yet taken effect, and when analgesic and anti-inflammatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs) have been unsatisfactory.

Systemic connective tissue diseases, vasculitic syndromes, and amyloidosis (supportive and symptomatic treatment in certain cases during the course of the underlying disease):

• Systemic lupus erythematosus (treatment of polyserositis and internal organ involvement); Sjögren's syndrome (treatment of pulmonary, renal, and cerebral involvement);
• Systemic sclerosis (treatment of myositis, pericarditis, and alveolitis);
• Polymyositis, dermatomyositis;
• Systemic vasculitides;
• Amyloidosis (replacement therapy in adrenal insufficiency).

Skin diseases:

• Pemphigus;
• Bullous dermatitis herpetiformis;
• Exfoliative dermatitis;
• Erythema exudativum (severe forms);
• Erythema nodosum;
• Seborrheic dermatitis (severe forms);
• Psoriasis (severe forms);
• Lichen;
• Urticaria unresponsive to standard treatment;
• Mycosis fungoides;
• Scleroderma;
• Angioedema (Quincke's edema).

Allergic diseases (unresponsive to standard treatment):

• Asthma, contact dermatitis, atopic dermatitis, serum sickness, allergic rhinitis, drug allergy, urticaria following blood transfusion.

Ocular diseases:

• Inflammatory eye diseases (acute central choroiditis, optic neuritis), allergic diseases (conjunctivitis, uveitis, scleritis, keratitis, iritis);
• Systemic immune diseases (sarcoidosis, temporal arteritis);
• Proliferative changes in the orbit (endocrine ophthalmopathy, pseudotumor);
• Sympathetic ophthalmia;
• Immunosuppressive therapy in corneal transplantation.

Gastrointestinal diseases:

• Ulcerative colitis (severe exacerbation), Crohn's disease (severe exacerbation), chronic autoimmune hepatitis, graft rejection following liver transplantation.

Respiratory tract diseases:

• Acute toxic bronchiolitis, chronic bronchitis, allergic bronchopulmonary aspergillosis, exogenous allergic alveolitis, idiopathic fibrosing alveolitis, sarcoidosis, eosinophilic infiltration, focal or disseminated pulmonary tuberculosis (in combination with appropriate antituberculosis therapy), tuberculous pleurisy (in combination with appropriate antituberculosis therapy), pleurisy in systemic connective tissue diseases, pulmonary vasculitis, berylliosis (granulomatous inflammation);
• Obliterative bronchitis caused by toxic gas poisoning;
• Radiation or aspiration pneumonitis.

Hematological diseases:

• Acquired or congenital chronic aplastic anemia, autoimmune hemolytic anemia, secondary thrombocytopenia in adults, erythroblastopenia, acute lymphoblastic leukemia (induction therapy), myelodysplastic syndrome, angioimmunoblastic T-cell lymphoma (in combination with cytostatics), plasmacytoma (in combination with cytostatics), severe anemia following myelofibrosis with myeloid metaplasia or lymphoplasmacytoid immunocytoma, systemic histiocytosis (systemic dependence).

Renal diseases:

• Primary and secondary glomerulonephritis (Goodpasture's syndrome), renal failure in systemic connective tissue diseases (systemic lupus erythematosus, Sjögren's syndrome), systemic vasculitis (usually in combination with cyclophosphamide), glomerulonephritis in polyarteritis nodosa, Churg–Strauss syndrome, Wegener's granulomatosis, Schönlein–Henoch purpura, mixed cryoglobulinemia, renal failure in Takayasu arteritis, interstitial nephritis, immunosuppressive therapy in kidney transplantation, induction of diuresis and reduction of proteinuria in idiopathic nephrotic syndrome (without uremia), and renal failure in systemic lupus erythematosus.

Oncological diseases:

• Palliative treatment of leukemia and lymphoma in adults, acute leukemia in children, hypercalcemia in malignant diseases.

Cerebral edema:

• Cerebral edema due to primary or metastatic brain tumor, craniotomy, and traumatic brain injury.

Other indications:

• Tuberculous meningitis with subarachnoid block (in combination with appropriate antituberculosis therapy), trichinosis with neurological symptoms or myocardial trichinosis, diagnostic testing for adrenal hyperfunction.

Contraindications.

Hypersensitivity to dexamethasone or to any other ingredient of the medicinal product. Acute viral, bacterial, or systemic fungal infections (unless appropriate therapy is administered), Cushing's syndrome, live vaccine administration, and breastfeeding (except in emergency situations).

Interaction with other medicinal products and other types of interactions.

Concomitant use of dexamethasone and NSAIDs increases the risk of gastrointestinal bleeding and ulcer formation.

The effect of dexamethasone is reduced when used simultaneously with drugs that induce the CYP 3A4 enzyme (phenytoin, phenobarbital, carbamazepine, primidone, rifabutin, rifampicin) or increase the metabolic clearance of glucocorticoids (ephedrine and aminoglutethimide); in these cases, the dose of dexamethasone should be increased. Interaction between dexamethasone and all the above-mentioned medicinal products may distort the results of the dexamethasone suppression test. This should be taken into account when evaluating test results.

Concomitant use of dexamethasone and drugs that inhibit CYP 3A4 enzyme activity (ketoconazole, macrolides) may lead to increased serum concentrations of dexamethasone. Dexamethasone is a moderate inducer of CYP 3A4. Concurrent use with drugs metabolized by CYP 3A4 (indinavir, erythromycin) may increase their clearance, resulting in decreased serum concentrations.

By inhibiting CYP 3A4 enzyme activity, ketoconazole may increase dexamethasone serum concentration. On the other hand, ketoconazole may suppress adrenal synthesis of glucocorticoids, thus adrenal insufficiency may develop due to decreased dexamethasone concentration.

Dexamethasone reduces the therapeutic effect of antidiabetic and antihypertensive agents, praziquantel, and sodium-losing diuretics (therefore, the dose of these drugs should be increased), but enhances the activity of heparin, albendazole, and potassium-sparing diuretics (the dose of these drugs should be reduced if necessary).

Dexamethasone may alter the effect of coumarin anticoagulants; therefore, prothrombin time should be monitored more frequently when this combination is used.

Concomitant use of high-dose glucocorticoids and β2-adrenergic agonists increases the risk of hypokalemia. In patients with hypokalemia, cardiac glycosides are more likely to cause arrhythmias and have greater toxicity.

Dexamethasone reduces the therapeutic effect of anticholinesterase agents used in myasthenia gravis.

Antacids reduce the absorption of dexamethasone in the stomach. The effect of dexamethasone when taken simultaneously with food and alcohol has not been studied, but concomitant intake of the drug with food high in sodium is not recommended. Smoking does not affect the pharmacokinetics of dexamethasone.

Glucocorticoids enhance renal clearance of salicylates, thus achieving therapeutic salicylate concentrations in serum may sometimes be difficult. Caution should be exercised in patients gradually reducing the corticosteroid dose, as increased serum salicylate concentrations and salicylate toxicity may occur.

If oral contraceptives are used concomitantly, the half-life of glucocorticoids may be prolonged, enhancing their biological effect and potentially increasing the risk of adverse effects.

Concomitant use of ritodrine and dexamethasone is contraindicated during labor, as it may lead to maternal death due to pulmonary edema. Cases of maternal death due to this condition have been reported.

Concomitant use of dexamethasone and thalidomide may cause toxic epidermal necrolysis.

Interactions with therapeutic benefits: concomitant administration of dexamethasone with metoclopramide, diphenhydramine, prochlorperazine, or 5-HT3 receptor antagonists (serotonin or 5-hydroxytryptamine, type 3 receptors, such as ondansetron or granisetron) is effective for the prevention of nausea and vomiting induced by chemotherapy with cisplatin, cyclophosphamide, methotrexate, or fluorouracil.

Concomitant use with CYP3A inhibitors, including drugs containing cobicistat, is expected to increase the risk of systemic adverse effects. Such combinations should be avoided unless the benefit outweighs the risk of systemic corticosteroid side effects. In such cases, patients should be monitored for systemic corticosteroid effects.

Special precautions for use.

Systemic use of corticosteroids may be accompanied by severe psychiatric reactions. Symptoms usually appear within a few days or weeks after initiation of treatment. The risk of developing these symptoms increases with high-dose therapy. Most reactions resolve upon dose reduction or discontinuation of the drug. Close monitoring and timely detection of changes in mental status, especially depressive mood, suicidal thoughts, and intentions, are essential. Corticosteroids should be used with particular caution in patients with a history of affective disorders, including patients with allergic reactions to any other medications, as well as in patients with such reactions in close relatives. Undesirable effects can be prevented by using the lowest effective doses for the shortest possible duration or by administering the required daily dose once in the morning.

In patients undergoing prolonged dexamethasone therapy, discontinuation of treatment may lead to withdrawal syndrome (without apparent signs of adrenal insufficiency), with symptoms such as fever, rhinitis, conjunctival hyperemia, headache, dizziness, somnolence or irritability, muscle and joint pain, vomiting, weight loss, general weakness, and frequent occurrence of seizures. Therefore, the dose of dexamethasone should be tapered gradually. Abrupt discontinuation may result in a fatal outcome.

If a patient experiences severe stress (due to trauma, surgery, or serious illness) during therapy, the dose of dexamethasone should be increased. If such stress occurs during discontinuation of therapy, hydrocortisone or cortisone should be administered.

Patients who have undergone prolonged dexamethasone therapy and experience severe stress after stopping treatment should resume dexamethasone therapy, as adrenal insufficiency induced by dexamethasone may persist for several months after discontinuation of treatment. Treatment with dexamethasone or natural glucocorticoids may mask symptoms of existing or new infections, as well as symptoms of intestinal perforation.

Dexamethasone may exacerbate systemic fungal infections, latent amoebiasis, and pulmonary tuberculosis.

Patients with active pulmonary tuberculosis should receive dexamethasone (in combination with anti-tuberculosis agents) only in cases of fulminant or severe disseminated pulmonary tuberculosis. Patients with inactive pulmonary tuberculosis receiving dexamethasone, or patients who are tuberculin-positive, should receive chemoprophylaxis.

Caution and medical supervision are recommended for patients with osteoporosis, arterial hypertension, heart failure, tuberculosis, glaucoma, hepatic or renal insufficiency, diabetes, active peptic ulcer, recent intestinal anastomosis, ulcerative colitis, and epilepsy. Special care is required for patients during the first weeks after myocardial infarction, patients with thromboembolism, myasthenia gravis, glaucoma, hypothyroidism, psychosis or psychoneurosis, and elderly patients.

During treatment, diabetes may worsen or latent diabetes may progress to clinical manifestation.

During prolonged therapy, serum potassium levels should be monitored.

Vaccination with live vaccines is contraindicated during dexamethasone treatment. Vaccination with inactivated viral or bacterial vaccines may not lead to the expected antibody synthesis and may lack the anticipated protective effect. Dexamethasone should generally be administered at least 8 weeks before vaccination and should not be initiated earlier than 2 weeks after vaccination.

Patients who have been treated with high doses of dexamethasone for a prolonged period and have never had measles should avoid contact with infected individuals; in case of accidental exposure, prophylactic treatment with immunoglobulin is recommended.

Caution is advised for patients recovering from surgery or bone fractures, as dexamethasone may delay wound healing and bone tissue formation.

The effect of glucocorticoids is enhanced in patients with liver cirrhosis or hypothyroidism.

Corticosteroids may distort the results of skin allergy tests.

In post-marketing studies, tumor lysis syndrome (TLS) has been observed in patients with hematological malignancies after administration of dexamethasone alone or in combination with other chemotherapeutic agents. Close monitoring of patients at high risk of TLS, such as those with high proliferation rates, large tumor burden, and high sensitivity to cytotoxic agents, is required, along with appropriate preventive measures.

Visual disturbances

Systemic and local glucocorticoid therapy may lead to visual disturbances. If blurred vision or other visual disturbances occur, patients should be referred for ophthalmological examination to determine the cause, which may include cataract, glaucoma, or the rare condition choroidopathy, which has been reported during systemic and local corticosteroid therapy.

Pheochromocytoma crisis

Pheochromocytoma crisis, which may be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should be prescribed to patients with suspected or diagnosed pheochromocytoma only after appropriate risk/benefit assessment.

Special warnings regarding excipients

The medicine contains lactose; therefore, it should not be administered to patients with rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding.

Pregnancy

Harmful effects on the fetus and newborn infant cannot be excluded. The medicinal product suppresses intrauterine fetal development. Dexamethasone may be administered to pregnant women only in exceptional emergency cases when the expected benefit to the mother outweighs the potential risk to the fetus. Particular caution is recommended in cases of preeclampsia. According to general recommendations for glucocorticoid therapy during pregnancy, the lowest effective dose necessary to control the underlying disease should be used. Infants born to mothers who received glucocorticoids during pregnancy should be carefully monitored for adrenal insufficiency.

Glucocorticoids cross the placenta and reach high concentrations in the fetus. Dexamethasone is less actively metabolized in the placenta than, for example, prednisone. Therefore, high concentrations of dexamethasone may be detected in fetal serum. According to some data, even pharmacological doses of glucocorticoids may increase the risk of placental insufficiency, oligohydramnios, delayed fetal development, or intrauterine fetal death, elevated white blood cell count (neutrophils) in the fetus, and adrenal insufficiency. There is no evidence confirming the teratogenic effect of glucocorticosteroids in humans. Administration of corticosteroids to pregnant animals has resulted in fetal developmental abnormalities, including cleft palate, intrauterine growth retardation, and effects on brain growth and development. There is no evidence that corticosteroids increase the frequency of congenital anomalies in humans, such as cleft palate/cleft lip.

Additional doses of glucocorticoids are recommended during childbirth for women who received glucocorticoids during pregnancy. In cases of prolonged labor or planned cesarean section, intravenous administration of 100 mg hydrocortisone every 8 hours is recommended.

Breastfeeding

A small amount of glucocorticoids passes into breast milk; therefore, women receiving dexamethasone should not breastfeed, especially when the drug is used above physiological levels (approximately 1 mg). This may lead to impaired infant growth and reduced secretion of endogenous corticosteroids.

Ability to affect reaction speed when driving or operating machinery.

Dexamethasone does not affect the ability to drive a car or operate machinery.

Method of Administration and Dosage

The dose should be determined individually according to the patient's specific condition, the intended duration of treatment, corticoid tolerance, and individual response.

Treatment

The recommended initial dose for adults is 0.5–9 mg per day. The maintenance dose is usually 0.5–3 mg per day. The daily dose may be divided into 2–4 administrations.

Initial doses of dexamethasone should be administered until a clinical response is achieved, after which the dose should be gradually reduced to the lowest clinically effective level. If high-dose oral therapy continues for longer than several days, the dose should be tapered gradually over several consecutive days or even longer periods (typically by 0.5 mg every three days). The maximum daily dose is usually 15 mg, while the minimum effective dose is 0.5–1 mg per day.

During prolonged high-dose therapy, dexamethasone should be taken with food, and antacids may be used between meals.

Dosage for Children

The recommended oral dose for replacement therapy is 0.02 mg/kg body weight or 0.67 mg/m² body surface area per day, administered in three divided doses.

For all other indications, the initial dose range is 0.08–0.3 mg/kg per day or 2.5–10 mg/m² body surface area per day, given in 3–4 divided doses.

Diagnostic Testing for Adrenal Hyperfunction

The dexamethasone suppression test (Liddle’s test) is performed as either a low-dose (small) or high-dose (large) test.

In the low-dose test, dexamethasone is administered at 0.5 mg every 6 hours for 48 hours (i.e., at 8 a.m., 2 p.m., 8 p.m., and 2 a.m.). Urinary excretion of 17-hydroxycorticosteroids or free cortisol is measured before and after dexamethasone administration. These dexamethasone doses suppress corticosteroid production in nearly all healthy individuals. Plasma cortisol levels measured 6 hours after the last dose should be less than 135–138 nmol/L (4.5–5 µg/100 mL). A reduction in urinary 17-hydroxycorticosteroid excretion to less than 3 mg/day or free cortisol to less than 54–55 nmol/day (19–20 µg/day) excludes adrenal hyperfunction. In patients with Cushing's disease or Cushing's syndrome, corticosteroid excretion remains unchanged during the low-dose test.

In the high-dose test, dexamethasone is administered at 2 mg every 6 hours for 48 hours (i.e., 8 mg of dexamethasone per day). Urine is collected to measure 17-hydroxycorticosteroids or free cortisol (and plasma free cortisol may be measured if necessary). In Cushing's disease, a reduction in 17-hydroxycorticosteroid or free cortisol excretion by 50% or more is typically observed, whereas in adrenal tumors or ectopic ACTH (or ectopic corticoliberin) syndrome, corticosteroid excretion remains unchanged. In some patients with ectopic ACTH syndrome, suppression of corticosteroid excretion does not occur even after administration of dexamethasone at a dose of 32 mg/day.

Equivalent Corticosteroid Doses

These dosage ratios apply only to oral or intravenous administration of these drugs. When these drugs or their derivatives are administered intramuscularly or intra-articularly, their relative properties may vary significantly.

Children.

May be used in children from birth only when absolutely necessary. Careful monitoring of growth and development in children and adolescents is required during treatment with dexamethasone. Preterm newborns: available data indicate long-term neurological adverse effects following early treatment (within 96 hours) of preterm infants with chronic lung disease when initial doses of 0.25 mg/kg twice daily are used.

Overdose.

There have been isolated reports of acute overdose or fatal outcomes due to acute overdose.

Overdose, typically only after several weeks of excessive dosing, may cause most of the adverse effects listed in the section "Adverse Reactions," particularly Cushing's syndrome.

Single ingestion of a large number of tablets does not lead to clinically significant intoxication. There is no specific antidote. Management of overdose should be supportive and symptomatic. Hemodialysis is not an effective method for accelerating the elimination of dexamethasone from the body.

Side effects.

Side effects during short-term treatment with dexamethasone

Immune system: hypersensitivity reactions.

Endocrine system: transient suppression of adrenal function.

Metabolism and nutrition: decreased carbohydrate tolerance, increased appetite and weight gain, hypertriglyceridemia.

Psychiatric disorders: psychiatric disorders.

Gastrointestinal disorders: peptic ulcer, acute pancreatitis.

Side effects during long-term treatment with dexamethasone

Immune system: reduced immune response and increased susceptibility to infections.

Endocrine system: persistent suppression of adrenal function, growth retardation in children and adolescents, premature closure of epiphyseal growth plates.

Metabolism and nutrition: obesity.

Eye disorders: cataract, glaucoma, chorioretinopathy.

Vascular disorders: hypertension, telangiectasia.

Skin and subcutaneous tissue: skin thinning.

Musculoskeletal and connective tissue: muscle atrophy, osteoporosis, aseptic bone necrosis, fractures of long bones.

Additional side effects that may occur in individual organs and systems during dexamethasone treatment:

Blood and lymphatic system: thromboembolic complications; decreased number of monocytes and/or lymphocytes; leukocytosis; eosinophilia (as with other glucocorticoids); thrombocytopenia and non-thrombocytopenic purpura.

Immune system: rash, bronchospasm, anaphylactic reactions, development of opportunistic infections.

Cardiac disorders: multifocal ventricular extrasystoles, transient bradycardia, heart failure, cardiac arrest, myocardial perforation due to previous myocardial infarction.

Vascular disorders: hypertensive encephalopathy.

Respiratory, thoracic and mediastinal disorders: reactivation of latent tuberculosis.

Nervous system: optic nerve edema and increased intracranial pressure (benign intracranial hypertension) after discontinuation of treatment; dizziness; vertigo; headache; seizures.

Psychiatric disorders: personality and behavioral changes, more commonly manifested as euphoria; insomnia, irritability, hyperkinesia, depression, nervousness, restlessness, manic-depressive psychosis, delirium, disorientation, hallucinations, paranoia, mood lability, suicidal thoughts, psychosis, sleep disturbances, confusion, amnesia, worsening of schizophrenia, worsening of epilepsy.

Endocrine system: suppression of adrenal function and adrenal atrophy (reduced response to stress), Cushing's syndrome, menstrual cycle disturbances, hirsutism.

Metabolism and nutrition: transition from latent to clinical manifestation of diabetes; increased requirement for insulin and oral antidiabetic drugs in patients with diabetes mellitus; sodium and water retention; increased potassium loss; hypokalemic alkalosis; negative nitrogen balance due to protein catabolism; hypocalcemia.

Gastrointestinal disorders: dyspepsia, vomiting, nausea, hiccup, gastric or duodenal peptic ulcer, esophagitis, gastrointestinal perforations and hemorrhages (hematemesis, melena), pancreatitis, gallbladder perforation, intestinal perforation (especially in patients with inflammatory bowel diseases).

Musculoskeletal and connective tissue disorders: muscle weakness, steroid myopathy (muscle weakness due to muscle catabolism), compression fractures of the spine, tendon ruptures (especially when used concomitantly with certain quinolones), joint cartilage damage and bone necrosis (with frequent intra-articular injections).

Skin and subcutaneous tissue: delayed wound healing, striae, petechiae and bruising, increased sweating, acne, suppression of skin tests, angioedema (Quincke's edema), allergic dermatitis, urticaria, pruritus.

Eye disorders: increased intraocular pressure; exophthalmos; exacerbation of bacterial, fungal or viral eye infections; corneal thinning, blurred vision.

Reproductive system and breast: impotence, amenorrhea.

General disorders and administration site conditions: transient burning and tingling sensation in the perineum following intravenous administration or high-dose administration; swelling, hyper- or hypopigmentation of the skin, skin and subcutaneous tissue atrophy, sterile abscess, erythema.

Symptoms of glucocorticoid withdrawal syndrome

In patients treated with dexamethasone for prolonged periods, too rapid dose reduction may lead to withdrawal syndrome, resulting in adrenal insufficiency, arterial hypotension, or even fatal outcome. In some cases, symptoms of withdrawal may resemble those of worsening or relapse of the underlying disease being treated. If severe adverse reactions occur, treatment must be discontinued.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging to protect from light and moisture. No special temperature conditions are required for storage of this medicinal product.

Keep out of reach of children.

Packaging.

10 tablets in a blister made of aluminum foil/film with OPa/Al/PVC, with 1, 2, 3, 5, 6, 9, or 10 blisters, perforated or non-perforated, in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

KRKA, d.d., Novo mesto / KRKA, d.d., Novo mesto.

Manufacturer's address and location of operations.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia.