Dexamethasone krka

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Dexamethasone Krka (Dexamethason KRKA)

Composition:

Active substance: dexamethasone;

1 tablet contains 20 mg or 40 mg of dexamethasone;

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

Pharmaceutical form. Tablets.

Main physico-chemical properties:

20 mg tablets: white or almost white, round tablets with bevelled edges, a score line and an engraving "20" on one side; the tablet can be divided into two equal parts along the score line;

40 mg tablets: white or almost white, oval tablets with a score line on both sides; the tablet can be divided into two equal parts along the score line.

Pharmacotherapeutic group. Corticosteroids for systemic use, glucocorticoids.

ATC code H02AB02.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Dexamethasone is a highly potent, long-acting glucocorticoid with minimal sodium-retaining capacity, making it particularly suitable for use in patients with heart failure and arterial hypertension.

Its anti-inflammatory effect is 7 times stronger than that of prednisolone. Like other glucocorticoids, dexamethasone exerts anti-allergic, antipyretic, and immunosuppressive effects.

The elimination half-life of dexamethasone ranges from 36 to 54 hours, allowing its use in conditions requiring continuous glucocorticoid activity.

Pharmacokinetics.

Absorption and distribution

Dexamethasone is well absorbed after oral administration. Peak plasma concentrations are reached within 1 to 2 hours after administration and show a wide range of interindividual variability. The mean elimination half-life is 3.6 ± 0.9 hours. Dexamethasone binds to plasma proteins (approximately 77%), primarily to albumin. The percentage of dexamethasone protein binding, unlike cortisol, remains virtually unchanged with increasing steroid concentrations. Corticosteroids rapidly distribute into all body tissues, cross the placenta, and may be excreted in small amounts in breast milk.

Biotransformation

Dexamethasone is metabolized mainly in the liver and also in the kidneys.

Elimination

Dexamethasone and its metabolites are excreted from the body via urine.

Clinical characteristics.

Indications.

Oncological diseases

Palliative treatment of tumors.

Prevention and treatment of vomiting induced by cytostatics, emetogenic chemotherapy in combination with antiemetic agents.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Systemic infection if appropriate anti-infective therapy is not used.

Peptic ulcer of the stomach or duodenum.

Vaccination with live vaccines during treatment with high therapeutic doses of dexamethasone (and other corticosteroids) due to the risk of viral infection.

Interaction with other medicinal products and other forms of interaction.

Before administering Dexamethasone KRKA in combination with any other medicinal product, the instructions for medical use of that medicinal product should be read.

Pharmacodynamic interactions

Patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs) should be monitored, as NSAIDs may increase the frequency and/or severity of gastric ulcers. Acetylsalicylic acid should be used with caution in combination with corticosteroids in hypoprothrombinemia.

Renal clearance of salicylates increases during corticosteroid therapy. Therefore, the dose of salicylates may need to be reduced when steroid treatment is discontinued. Discontinuation of steroid therapy may lead to increased salicylate intoxication due to elevated serum concentrations.

Corticosteroids reduce the effect of antidiabetic agents such as insulin, sulfonylureas, and metformin. Hyperglycemia and diabetic ketoacidosis may occasionally occur.

Therefore, diabetic patients should have blood and urine tests more frequently at the beginning of treatment. The hypokalemic effect of acetazolamide injections, loop diuretics, thiazide diuretics, potassium-wasting diuretics, amphotericin B, glucomineralocorticosteroids, tetracosactide, and laxatives will be enhanced. Hypokalemia may lead to cardiac arrhythmias, particularly torsade de pointes, and increases the toxicity of cardiac glycosides. Hypokalemia should be corrected before initiating corticosteroid therapy, and electrolyte levels should be determined and ECG performed. In addition, concomitant use of amphotericin B and hydrocortisone has been reported to cause cardiac enlargement and heart failure.

Anti-ulcer agents. Carbenoxolone increases the risk of hypokalemia.

Chloroquine, hydroxychloroquine, and mefloquine. Increased risk of myopathy and cardiomyopathy.

Concomitant use with ACE inhibitors increases the risk of hematological disorders. Corticosteroids may affect the antihypertensive effect of antihypertensive drugs. Doses of antihypertensive agents may need to be adjusted during dexamethasone therapy.

Thalidomide. Particular caution is required when used concomitantly with thalidomide, as cases of toxic epidermal necrolysis have been reported.

Vaccination efficacy may be reduced during dexamethasone treatment.

Vaccination with live vaccines during treatment with high therapeutic doses of dexamethasone (and other corticosteroids) is contraindicated due to the risk of viral infection. In such cases, vaccination should be postponed for at least 3 months after completion of corticosteroid therapy. Other forms of immunization during treatment with high therapeutic doses of corticosteroids are hazardous due to the risk of neurological complications and lower or absent increases in antibody titers (compared to expected values), resulting in reduced protective effect. However, patients who have used corticosteroids locally or for a short period (less than 2 weeks) in lower doses may be vaccinated.

Cholinesterase inhibitors. Concomitant use of cholinesterase inhibitors and corticosteroids may result in severe muscle weakness in patients with myasthenia gravis. If possible, cholinesterase inhibitors should be discontinued at least 24 hours before starting corticosteroid therapy.

There is an increased risk of tendinitis and tendon rupture in patients receiving concomitant glucocorticoids and fluoroquinolones.

Pharmacokinetic interactions

Effect of other medicinal products on dexamethasone

Dexamethasone is metabolized via cytochrome P450 3A4 (CYP3A4).

Concomitant use of dexamethasone with CYP3A4 inducers such as ephedrine, barbiturates, rifabutin, rifampicin, phenytoin, and carbamazepine may lead to decreased plasma concentrations of dexamethasone; therefore, the dose of dexamethasone may need to be increased.

Aminoglutethimide may accelerate dexamethasone elimination and reduce its efficacy. If necessary, appropriate dose adjustment of dexamethasone should be performed.

Bile acid resins such as cholestyramine may reduce dexamethasone absorption.

Locally acting gastrointestinal agents, antacids, activated charcoal. Reduced absorption of glucocorticoids has been described when used concomitantly with prednisolone and dexamethasone. Therefore, glucocorticoids and locally acting gastrointestinal agents, antacids, or activated charcoal should be administered with an interval of at least two hours.

Concomitant use of dexamethasone with CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole), HIV protease inhibitors (e.g., ritonavir), and macrolides (e.g., erythromycin) may lead to increased plasma concentrations and reduced clearance of dexamethasone. If necessary, the dose of dexamethasone should be reduced.

Ketoconazole may not only increase dexamethasone plasma concentrations by inhibiting CYP3A4 but may also suppress adrenal corticosteroid synthesis and cause adrenal insufficiency after discontinuation of corticosteroid therapy.

Estrogens, including oral contraceptives, may inhibit the metabolism of certain corticosteroids and thereby enhance their effect.

Effect of dexamethasone on other medicinal products

Dexamethasone is a moderate inducer of CYP3A4. Concomitant use of dexamethasone with drugs metabolized by CYP3A4 may lead to increased clearance and decreased plasma concentrations of these drugs.

Antituberculosis agents. Decreased plasma concentrations of isoniazid have been observed when used concomitantly with prednisolone. Close monitoring of patients taking isoniazid is required.

Cyclosporine. Concomitant use of cyclosporine and corticosteroids may enhance the effect of both drugs. There is an increased risk of cerebral seizures.

Praziquantel. Reduced plasma concentrations of praziquantel may lead to treatment failure due to increased hepatic metabolism induced by dexamethasone.

Oral anticoagulants (coumarins). Concomitant corticosteroid therapy may potentiate or weaken the effect of oral anticoagulants. When high doses are used or treatment duration exceeds 10 days, there is an increased risk of bleeding specific to corticosteroid therapy (gastrointestinal mucosa damage, vascular fragility). Patients receiving corticosteroids in combination with oral anticoagulants should be closely monitored (control on day 8, then every two weeks during and after treatment).

Atropine and other anticholinergic agents. Increased intraocular pressure may occur when used concomitantly with dexamethasone.

Non-depolarizing muscle relaxants. Muscle relaxation effect may be prolonged.

Somatotropin. Growth hormone effect may be reduced.

Protirelin. The expected increase in TSH may be diminished during protirelin administration.

Concomitant use of 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 increased risk of systemic corticosteroid side effects, and in such cases, patients should be monitored for systemic corticosteroid effects.

Special precautions for use.

Adrenal insufficiency

Adrenal insufficiency caused by glucocorticoid therapy may persist for many months and, in some cases, more than one year after discontinuation of treatment, depending on the dose and duration of therapy. During dexamethasone treatment, temporary dose increases may be required in individual cases of physical stress (e.g., trauma, surgical procedures, childbirth, etc.). Due to the potential risk under stressful conditions, initial corticosteroid administration should be considered in patients undergoing prolonged therapy. Even after prolonged adrenal insufficiency following discontinuation of treatment, glucocorticoid administration may be necessary in patients experiencing severe stress. Acute adrenal insufficiency induced by therapy can be minimized by gradually tapering the dose before planned discontinuation of the drug.

Dexamethasone treatment should only be administered strictly according to indications, and, when necessary, additional targeted anti-infective therapy should be provided for the following diseases and conditions:

• Acute viral infections (herpes zoster, herpes simplex virus, varicella, herpetic keratitis);
• HBsAg-positive chronic hepatitis in the active phase;
• Approximately 8 weeks before and 2 weeks after live vaccination (see sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction");
• Systemic mycoses and parasitoses (e.g., nematodes);
• Poliomyelitis;
• Lymphadenitis following BCG vaccination;
• Acute and chronic bacterial infections;
• Tuberculosis in medical history (risk of reactivation), only with concomitant use of antituberculosis agents;
• Known or suspected strongyloidiasis (nematode infestation). Glucocorticoid treatment may lead to strongyloidiasis hyperinfection and widespread larval migration.

Furthermore, dexamethasone treatment should only be prescribed when strict indications are present, and additional specific treatment should be considered for the following conditions:

• Gastrointestinal ulcers;
• Severe osteoporosis (since corticosteroids negatively affect calcium balance);
• Hypertension that is difficult to control;
• Diabetes mellitus that is difficult to control;
• Psychiatric disorders (including history);
• Closed-angle glaucoma and open-angle glauopenia;
• Corneal ulcers and corneal trauma;
• Severe heart failure.

Anaphylactic reactions

Severe anaphylactic reactions may occur.

Tendinitis

There is an increased risk of developing tendinitis and tendon rupture in patients receiving concomitant glucocorticoids and fluoroquinolones.

Myasthenia

Pre-existing myasthenia may worsen at the beginning of dexamethasone treatment.

Visual disturbances

Cases of visual disturbances have been reported with both systemic and local use of corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, they should be referred to an ophthalmologist for evaluation of possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR), reported after systemic and local corticosteroid use.

Prolonged use of corticosteroids may lead to posterior subcapsular cataract, glaucoma with possible optic nerve damage, and may increase the risk of secondary ocular infections caused by fungi or viruses.

Corticosteroids should be used with caution in patients with ocular herpes due to the potential risk of corneal perforation.

Intestinal perforation

Due to the risk of intestinal perforation, dexamethasone should only be used under emergency indications and with appropriate monitoring in the following conditions:

• Severe ulcerative colitis with risk of perforation;
• Diverticulitis;
• Enteric anastomosis (immediately after surgery).

Signs of peritoneal irritation following gastrointestinal perforation may be absent in patients receiving high doses of glucocorticoids.

Diabetes mellitus

Increased insulin or oral antidiabetic drug requirements should be considered in diabetic patients receiving dexamethasone.

Cardiovascular system disorders

Regular monitoring of blood pressure is required in patients during dexamethasone treatment, especially when high doses are used and in patients with difficult-to-control hypertension. Careful monitoring is necessary in patients with severe heart failure due to the risk of worsening.

Bradycardia may occur in patients receiving high doses of dexamethasone.

Corticosteroids should be used with caution in patients who have recently suffered myocardial infarction, as cases of myocardial rupture have been reported.

Infections

Dexamethasone treatment may mask symptoms of existing or developing infections, complicating diagnosis. Prolonged use of even small doses of dexamethasone increases the risk of infection, even by microorganisms that rarely cause infections otherwise (so-called opportunistic infections).

Vaccination

Inactivated vaccines may be administered. However, it should be noted that higher corticosteroid doses may negatively affect immune response and thus reduce vaccination efficacy. During prolonged dexamethasone treatment, regular medical check-ups (including preventive eye examinations every three months) are recommended.

Metabolic disturbances

With high doses, monitoring of adequate calcium intake and sodium restriction, as well as serum potassium levels, is recommended. Depending on the duration and dosage of treatment, a negative effect on calcium metabolism may be expected; therefore, osteoporosis prevention is advised. This particularly applies to concomitant risk factors such as family predisposition, advanced age, postmenopausal period, inadequate protein and calcium intake, smoking, excessive alcohol consumption, and insufficient physical activity. Prevention includes adequate calcium and vitamin D intake and physical activity. Additional medical treatment should be considered in cases of existing osteoporosis.

Corticosteroids should be prescribed with caution to patients with migraine, as corticosteroid use may lead to fluid retention.

Psychological changes

Psychological changes may manifest in various forms, the most common being euphoria. Depression, psychotic reactions, and suicidal tendencies may also occur.

These conditions can be serious. They usually begin within days or weeks after starting treatment and are more likely with high-dose regimens. Most of these effects resolve with dose reduction or discontinuation of the drug. If such effects occur, patients may require treatment. In some cases, mental health problems have appeared during dose tapering or after discontinuation.

Brain edema and increased intracranial pressure

Corticosteroids should not be used in traumatic brain injury, as they are unlikely to be beneficial and may even be harmful.

Tumor lysis syndrome

Tumor lysis syndrome (TLS) has been observed in patients with hematological malignancies after dexamethasone administration 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.

Discontinuation of treatment

Glucocorticoid doses should be gradually tapered.

The following risks should be considered when interrupting or discontinuing prolonged glucocorticoid therapy:

• Exacerbation or relapse of the underlying disease, acute adrenal insufficiency, corticosteroid withdrawal syndrome (withdrawal syndrome may include fever, muscle and joint pain, nasal mucosal inflammation (rhinitis), weight loss, skin itching, and eye inflammation (conjunctivitis)).
• Some viral diseases (e.g., varicella, measles) in patients receiving glucocorticoids may have a severe course.
• Children and adults with weakened immune systems who have not had varicella or measles are particularly susceptible to adverse effects. If such individuals are exposed to measles or varicella during dexamethasone treatment, prophylactic treatment may be required.

Other

A pheochromocytoma crisis, which may be fatal, has been reported after systemic corticosteroid use. Corticosteroids should be administered to patients with suspected or confirmed pheochromocytoma only after appropriate risk-benefit assessment.

Children

Corticosteroids cause dose-dependent growth suppression in infants, children, and adolescents, as they may lead to premature epiphyseal closure, which can be irreversible. Therefore, strict indications are required for prolonged dexamethasone use in children, and growth in such patients should be monitored regularly.

Preterm newborns: Available data indicate long-term neurodevelopmental adverse effects after early treatment (< 96 hours) of preterm infants with chronic lung disease at initial doses of 0.25 mg/kg twice daily.

Geriatric patients

Adverse reactions to systemic corticosteroids, especially in elderly patients, may have serious consequences. These mainly include osteoporosis, arterial hypertension, hypokalemia, diabetes mellitus, increased susceptibility to infections, and skin atrophy. Careful clinical monitoring is necessary to prevent life-threatening reactions.

Effect on diagnostics

Glucocorticoids may suppress skin reactions in allergy testing. They may also affect the nitroblue tetrazolium test for detecting bacterial infections and may lead to false-negative results.

Note on doping

Dexamethasone use may result in a positive doping test.

The medicinal product Dexamethasone KRKA contains lactose. Patients with rare hereditary conditions associated with galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this product.

Use during pregnancy or breastfeeding.

Pregnancy

Dexamethasone crosses the placenta. Administration of corticosteroids to pregnant animals may cause 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 such as cleft palate/cleft lip in humans. Long-term or repeated corticosteroid therapy during pregnancy increases the risk of intrauterine growth retardation. Newborns exposed to corticosteroids before birth have an increased risk of adrenal insufficiency, which normally undergoes spontaneous postnatal regression, although this is rarely clinically significant. Dexamethasone should be used during pregnancy, especially in the first trimester, only if the benefit outweighs the risks to the mother and fetus.

Lactation

Corticosteroids pass into breast milk. There is insufficient information on the passage of dexamethasone into breast milk. Risk to newborns/infants cannot be excluded. Infants whose mothers receive high doses of systemic corticosteroids over a prolonged period may have suppressed adrenal function.

The decision to continue or discontinue breastfeeding and/or continue or discontinue dexamethasone therapy should be made considering the benefits of breastfeeding for the child and the benefits of dexamethasone therapy for the mother.

Fertility

Dexamethasone reduces testosterone biosynthesis and endogenous ACTH secretion, affecting spermatogenesis and the ovarian cycle.

Ability to influence reaction speed when driving or operating machinery.

Studies on the effect on the ability to drive or operate machinery have not been conducted.

Dexamethasone may cause confusion, hallucinations, dizziness, somnolence, fatigue, syncope, and blurred vision. During dexamethasone treatment, patients should be informed not to drive, operate machinery, or perform hazardous tasks.

Administration and dosage.

Dosage

Please note that these are high doses of the medicinal product. It is recommended to use the lowest effective dose of Dexamethasone Krka.

Dexamethasone is administered in usual doses ranging from 0.5 mg to 10 mg daily, depending on the disease being treated. In more severe conditions, doses exceeding 10 mg daily may be required. The dose should be adjusted according to the individual patient's response and the severity of the disease. The initial dose of dexamethasone is administered until a clinical response is achieved, after which the dose should be gradually reduced to the lowest clinically effective dose. Significantly higher doses are used for the treatment of acute severe conditions compared to chronic diseases. To minimize adverse reactions, the lowest effective dose should be used.

If otherwise not specified, the following dosage recommendations should be followed.

The dosage recommendations below are provided for informational purposes only. Initial and daily doses must always be determined based on the individual patient's response and the severity of the disease.

Palliative treatment of tumor diseases: the initial dose and duration of treatment depend on the cause and severity of the disease, 3–20 mg daily. Very high doses (up to 96 mg) may also be used for palliative treatment. For optimal dosing and to reduce the number of tablets, a combination of low doses (4 mg and 8 mg) and higher doses (20 mg or 40 mg) can be used.

Prevention and treatment of vomiting induced by cytostatic agents, emetogenic chemotherapy, in combination with antiemetic agents: orally 10–20 mg of dexamethasone before the start of chemotherapy, followed, if necessary, by 4–8 mg 2–3 times daily for 1–3 days (for moderate emetogenic therapy) and up to 6 days (for intensive emetogenic therapy).

Renal impairment

In patients undergoing active hemodialysis, the clearance of the drug may increase through the dialysate, so dose adjustment of steroids may be required.

Hepatic impairment

Patients with severe liver disease may require dose adjustment. In patients with severe hepatic insufficiency, the biological effects of dexamethasone may be enhanced due to slower metabolism (prolonged plasma half-life) and hypoalbuminemia (increased free drug concentration in plasma), which may also lead to more adverse reactions.

Elderly patients

Treatment of elderly patients, especially over prolonged periods, should take into account the more serious consequences of common corticosteroid adverse reactions in this population (osteoporosis, diabetes mellitus, arterial hypertension, reduced immunity, psychiatric changes). In such patients, plasma concentrations of dexamethasone may be higher and excretion slower compared to younger patients, so the dose should be appropriately reduced.

Long-term treatment

For long-term treatment of certain diseases after initial therapy, glucocorticoid treatment should be switched from dexamethasone to prednisone/prednisolone to reduce suppression of adrenal cortex function.

Discontinuation of treatment

Acute adrenal insufficiency may occur after abrupt discontinuation of prolonged high-dose glucocorticoid therapy. Therefore, in such cases, glucocorticoid doses should be gradually tapered to discontinue treatment (see section "Special precautions").

Administration method

Dexamethasone should be taken during or immediately after meals to minimize gastrointestinal irritation. Consumption of alcoholic or caffeinated beverages should be avoided.

Dexamethasone KRKA is available in tablet form containing 4 mg, 8 mg, 20 mg, and 40 mg. Tablets can be divided into equal parts to provide additional doses of 2 mg and 10 mg, facilitating tablet swallowing for the patient. When alternate-day therapy is not feasible, the total daily dose of glucocorticoids can usually be administered as a single morning dose; however, some patients may require splitting of the daily glucocorticoid doses.

Children.

The range of initial doses of dexamethasone is 0.08–0.3 mg/kg daily or 2.5 mg–10 mg/m² body surface area daily, administered in 3–4 divided doses. Dexamethasone elimination is approximately similar in children and adults when the dose is adjusted according to body surface area. Dosing should be individualized considering the potential impact on growth and development and the presence of signs of adrenal suppression. Preterm neonates: available data indicate prolonged neurological adverse reactions after early treatment (within 96 hours) of preterm infants with chronic lung disease at initial doses of 0.25 mg/kg twice daily.

Overdose.

Symptoms

Acute toxicity and/or fatal cases following glucocorticoid overdose have been rarely reported.

Overdose or prolonged use may exacerbate glucocorticoid side effects.

Treatment

No antidote exists. Treatment is symptomatic and supportive. Gradual reduction of the dexamethasone dose or slow discontinuation is expected, if possible. Treatment is likely unnecessary for reactions arising from chronic intoxication, unless the patient's condition renders them exceptionally susceptible to the negative effects of corticosteroids. In such cases, gastric lavage should be performed and symptomatic treatment initiated as needed. Anaphylactic reactions and hypersensitivity reactions can be treated with epinephrine (adrenaline), artificial ventilation with positive pressure, and aminophylline. The patient should be kept warm and at rest. The plasma half-life of dexamethasone is approximately 190 minutes.

Side effects.

Summary of safety profile

The frequency of expected adverse reactions correlates with the relative potency of the substance, dose, duration of administration, and length of treatment. The risk of adverse reactions is low during short-term therapy provided that dosage recommendations are followed and careful patient monitoring is performed.

Common adverse reactions associated with short-term treatment with dexamethasone (days/weeks) include weight gain, psychiatric disorders, impaired glucose tolerance, and transient adrenal insufficiency. Long-term treatment with dexamethasone (months/years) usually causes central obesity, skin fragility, muscle atrophy, osteoporosis, growth retardation, and long-term adrenal insufficiency (see also section "Special precautions").

System Organ Classes	Adverse Reactions (frequency unknown)
Infections and infestations	Increased susceptibility to infections* or exacerbation of latent infections, including sepsis, tuberculosis, ocular infections, chickenpox, measles, fungal and viral infections, with masking of clinical symptoms; opportunistic infections
Blood and lymphatic system	Leukocytosis, lymphopenia, eosinopenia, polycythemia, coagulation disorders
Immune system	Allergic reactions, including anaphylaxis, decreased immunity (see also "Infections and infestations").
Endocrine system	Suppression of the hypothalamic-pituitary-adrenal axis and induction of Cushing's syndrome (typical symptoms: moon face, facial flushing (plethora), central obesity), secondary adrenal and pituitary insufficiency* (especially under stress such as trauma or surgery), growth suppression in infants, children, and adolescents, menstrual irregularities and amenorrhea, hirsutism
Metabolism and nutrition	Weight gain, negative protein and calcium balance, increased appetite, sodium and water retention, potassium loss* (caution: arrhythmia), hypokalemic alkalosis, manifestation of latent diabetes mellitus, impaired carbohydrate tolerance requiring increased doses of antidiabetic agents*, hypercholesterolemia, hypertriglyceridemia
Psychiatric*	Psychological dependence, depression, insomnia, exacerbation of schizophrenia, psychiatric disorders ranging from euphoria to severe psychosis
Nervous system	Increased intracranial pressure with papilledema in children (idiopathic intracranial hypertension), usually after discontinuation of treatment; manifestation of latent epilepsy, increased frequency of seizures in existing epilepsy, dizziness, headache
Eye organs	Increased intraocular pressure, glaucoma*, papilledema, cataract*, mainly posterior subcapsular opacity, corneal and scleral atrophy, increased incidence of viral, fungal, and bacterial ocular infections, worsening of symptoms related to corneal ulcers*, blurred vision, chorioretinopathy
Cardiac	Rupture of cardiac muscle following recent myocardial infarction, congestive heart failure in predisposed patients, cardiac decompensation*
Vascular	Arterial hypertension, vasculitis, increased atherosclerosis and risk of thrombosis/embolism (increased blood coagulation may lead to thromboembolic complications)
Respiratory, thoracic and mediastinal	Hiccups
Gastrointestinal	Dyspepsia, abdominal distension*, gastric ulcers with perforation and hemorrhage, acute pancreatitis, ulcerative esophagitis, esophageal candidiasis, flatulence, nausea, vomiting, hiccups
Skin and subcutaneous tissue	Hypertrichosis, skin atrophy, telangiectasias, striae, erythema, steroid acne, petechiae, ecchymoses, allergic dermatitis, urticaria, angioneurotic edema, hair thinning, pigmentary disturbances, increased capillary fragility, perioral dermatitis, hyperhidrosis, tendency to bruise
Musculoskeletal and connective tissue	Premature epiphyseal closure, osteoporosis, vertebral and long bone fractures, aseptic necrosis of femoral and humeral heads, tendon rupture*, proximal myopathy, muscle weakness, loss of muscle mass
Reproductive system and breast	Impotence
General	Reduced response to vaccination and skin tests. Delayed wound healing, discomfort, malaise, corticosteroid withdrawal syndrome: too rapid dose reduction after prolonged therapy may result in acute adrenal insufficiency, hypotension, and death. Withdrawal syndrome may present as fever, myalgia, arthralgia, rhinitis, conjunctivitis, development of painful, itchy skin nodules, and weight loss.

*See also section "Special precautions for use".

Description of selected adverse reactions

Adrenal insufficiency

Adrenal insufficiency caused by glucocorticoid therapy may persist for many months and, in some cases, over a year after discontinuation of treatment, depending on the dose and duration of therapy (see section "Special precautions for use").

Psychiatric disturbances

Psychiatric disturbances may manifest in various forms, the most common being euphoria. Depression, psychotic reactions, and suicidal tendencies are also possible. These disorders can be serious and usually occur within a few days or weeks after starting treatment. They are more likely to occur with high-dose therapy. Most of these problems resolve upon dose reduction or discontinuation of the drug (see section "Special precautions for use").

Infections

Dexamethasone treatment may mask signs of existing or developing infections. This complicates diagnosis and may lead to an increased risk of infection (see section "Special precautions for use").

Gastrointestinal perforation

Corticosteroids may be associated with an increased risk of colonic perforation in severe ulcerative colitis with impending perforation, diverticulitis, and enteric anastomosis (immediately after surgery).

Signs of peritoneal irritation following gastrointestinal tract perforation may be absent in patients receiving high doses of glucocorticoids (see section "Special precautions for use").

Cardiovascular disorders

Bradycardia, worsening of severe heart failure, and poorly controlled hypertension may occur. Corticosteroids should be used with caution in patients who have recently suffered myocardial infarction, as cases of myocardial rupture have been reported (see section "Special precautions for use").

Children

Corticosteroids may cause dose-dependent growth retardation in infants, children, and adolescents, as corticosteroids may lead to premature closure of epiphyses, which may be irreversible (see section "Special precautions for use").

Elderly patients

Adverse effects of systemic corticosteroids may have serious consequences, particularly in elderly patients. These mainly include osteoporosis, arterial hypertension, hypokalemia, diabetes mellitus, increased susceptibility to infections, and skin atrophy (see section "Special precautions for use").

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance System at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

No special temperature storage conditions are required for this medicinal product.

Keep in the original packaging to protect from light and moisture.

Keep out of reach of children.

Packaging.

20 mg: 10 tablets in a blister; 1, 2 or 3 blisters in a cardboard box.

40 mg: 5 tablets in a blister; 2, 4 or 6 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

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

Manufacturer's address and place of business.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia / Smarjeska cesta 6, 8501 Novo mesto, Slovenia.