Dexamethasone

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXAMETHASONE

Composition:

Active substance: dexamethasone;

1 ml of solution contains 4 mg of dexamethasone sodium phosphate;

Excipients: propylene glycol, glycerol, phosphate buffer solution, disodium edetate, methylparahydroxybenzoate (E 218), propylparahydroxybenzoate (E 216), water for injections.

Medicinal form. Solution for injection.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Corticosteroids for systemic use. Glucocorticoids. ATC code H02A B02.

Pharmacological properties.

Pharmacodynamics. Dexamethasone is a synthetic adrenocortical hormone (corticosteroid) that exerts glucocorticoid activity. It produces anti-inflammatory and immunosuppressive effects and also influences energy metabolism, glucose metabolism, and (via negative feedback) the secretion of hypothalamic activation factor and tropic hormones of the adenohypophysis.

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. Within the cell cytoplasm, two well-defined receptor systems exist. By binding to glucocorticoid receptors, corticosteroids exert anti-inflammatory and immunosuppressive effects and regulate glucose metabolism; through 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, enhancing 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 GRE or specific genes, modulates mRNA transcription, which may be either increased or decreased. The newly formed mRNA is transported to the ribosome, leading to the synthesis of new proteins. Depending on the target cells and cellular processes involved, 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, glucocorticoids can be considered to affect most cells in the body.

Clinical efficacy and safety in the treatment of COVID-19

Clinical efficacy

An individual, randomized, controlled, open-label, adaptive platform trial RECOVERY (Randomised Evaluation of Covid-19 Therapy)¹, initiated by investigators, was conducted to evaluate outcomes of potential treatments in patients hospitalized with COVID-19.

The trial was conducted across 176 hospitals in the United Kingdom. A total of 6425 patients were randomized to receive either dexamethasone (2104 patients) or usual care (4321 patients). Laboratory-confirmed SARS-CoV-2 infection was present in 89% of patients.

At randomization, 16% of patients were receiving invasive mechanical ventilation or extracorporeal membrane oxygenation, 60% received oxygen alone (with or without non-invasive ventilation), and 24% received neither.

The mean age of patients was 66.1 ± 15.7 years. Women comprised 36% of the study population. Medical history included diabetes in 24%, heart disease in 27%, and chronic lung disease in 21%.

Primary endpoint

Mortality at day 28 was significantly lower in the dexamethasone group compared to the usual care group: 482 of 2104 patients (22.9%) versus 1110 of 4321 patients (25.7%), respectively (rate ratio 0.83; 95% confidence interval (CI) 0.75–0.93; P < 0.001).

Among patients receiving invasive mechanical ventilation, the dexamethasone group had lower mortality than the usual care group (29.3% vs. 41.4%; rate ratio 0.64; 95% CI 0.51–0.81). Similarly, among patients receiving oxygen without invasive ventilation, mortality was lower in the dexamethasone group (23.3% vs. 26.2%; rate ratio 0.82; 95% CI 0.72–0.94).

There was no clear benefit of dexamethasone among patients who did not require respiratory support at randomization (17.8% vs. 14.0%; rate ratio 1.19; 95% CI 0.91–1.55).

Secondary endpoint

Hospitalization duration was shorter in the dexamethasone group compared to the usual care group (median 12 days vs. 13 days), and the probability of hospital discharge within 28 days was higher (rate ratio 1.10; 95% CI 1.03–1.17).

Consistent with the primary endpoint, the greatest reduction in hospitalization duration by day 28 was observed in patients receiving invasive mechanical ventilation at randomization (rate ratio 1.48; 95% CI 1.16–1.90). A somewhat smaller effect was seen in patients receiving oxygen alone (rate ratio 1.15; 95% CI 1.06–1.24). No beneficial effect was observed in patients not receiving oxygen (rate ratio 0.96; 95% CI 0.85–1.08).

* The ratio of outcomes was adjusted for age based on 28-day mortality and hospital discharge results. The risk ratios were adjusted for age regarding the outcome of receiving invasive mechanical ventilation or death, and its components.

† Patients who received invasive mechanical ventilation at randomization were excluded from this category.

Safety

During the study, 4 serious adverse events related to the investigational treatment were recorded: 2 cases of hyperglycemia, 1 case of steroid-induced psychosis, and 1 case of upper gastrointestinal tract bleeding. All events were resolved.

Subgroup Analysis

Effects of dexamethasone on 28-day mortality, according to age and respiratory support received at randomization²

Effects of dexamethasone on 28-day mortality, according to respiratory support modality and presence of any chronic comorbidity, obtained at randomization3

1 www.recoverytrial.net

2, 3 (source: Horby P. et al., 2020; https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1;

doi: https://doi.org/10.1101/2020.06.22.20137273).

Pharmacokinetics. After intravenous administration, peak plasma concentrations of dexamethasone phosphate are achieved within just 5 minutes, while after intramuscular administration, they are reached within 1 hour. When administered locally by injection into joints or soft tissues, absorption is slower. The effect of the drug begins rapidly after intravenous administration. Following intramuscular administration, clinical effects are observed approximately 8 hours after injection. The duration of action is prolonged: from 17 to 28 days after intramuscular administration and from 3 days to 3 weeks after local application. The biological half-life of dexamethasone ranges from 24 to 72 hours. In plasma and synovial fluid, dexamethasone phosphate is rapidly converted into dexamethasone.

Approximately 77% of dexamethasone in plasma is protein-bound, primarily to albumin. Only a small amount binds to other plasma proteins. Dexamethasone is a lipophilic substance and therefore distributes into extracellular and intracellular spaces. It exerts its effects in the central nervous system (hypothalamus, pituitary gland) by binding to membrane receptors. In peripheral tissues, it binds and acts via cytoplasmic receptors. Dexamethasone is metabolized at the site of its action, i.e., within the cell. Dexamethasone is primarily metabolized in the liver. Small amounts of dexamethasone are metabolized in the kidneys and other tissues. The main route of elimination is via the kidneys.

Clinical characteristics.

Indications. Dexamethasone is administered intravenously or intramuscularly in emergency situations and when oral administration is not feasible in the following conditions:

Endocrine disorders:

• Replacement therapy for primary or secondary (pituitary) adrenal insufficiency (hydrocortisone or cortisone are drugs of choice; synthetic analogs may be used as needed, often in combination with mineralocorticoids; in pediatric practice, concomitant use with mineralocorticoids is extremely important);
• Acute adrenal insufficiency (hydrocortisone or cortisone are drugs of choice; combination with mineralocorticoids may be necessary, especially when synthetic analogs are used);
• Preoperatively and in cases of severe trauma or illness in patients with established adrenal insufficiency or uncertain adrenocortical reserve;
• Shock unresponsive to conventional therapy, when adrenal insufficiency is present or suspected;
• Congenital adrenal hyperplasia;
• Nonsuppurative thyroiditis;
• Hypercalcemia associated with malignancy.

Rheumatic diseases: as adjunctive therapy for short-term use (to control acute episodes or flares) in:

• Post-traumatic osteoarthritis;
• Synovitis associated with osteoarthritis;
• Rheumatoid arthritis, including juvenile rheumatoid arthritis (some cases may require low-dose maintenance therapy);
• Epicondylitis;
• Acute and subacute bursitis;
• Acute nonspecific tenosynovitis;
• Acute gouty arthritis;
• Psoriatic arthritis;
• Ankylosing spondylitis.

Collagen diseases: during periods of exacerbation or as supportive therapy in selected cases of:

• Systemic lupus erythematosus;
• Acute rheumatic carditis.

Skin diseases:

• Pemphigus;
• Severe multiforme erythema (Stevens–Johnson syndrome);
• Exfoliative dermatitis;
• Bullous dermatitis herpetiformis;
• Severe seborrheic dermatitis;
• Severe psoriasis;
• Mycosis fungoides.

Allergic diseases: control of severe or disabling allergic conditions unresponsive to conventional treatment:

• Bronchial asthma;
• Contact dermatitis;
• Atopic dermatitis;
• Serum sickness;
• Chronic or seasonal allergic rhinitis;
• Drug allergy;
• Transfusion-related urticaria;
• Acute noninfectious laryngeal edema (epinephrine is the drug of choice).

Ophthalmic diseases: severe acute and chronic allergic and inflammatory processes involving the eye:

• Ocular involvement due to Herpes zoster;
• Iritis, iridocyclitis;
• Chorioretinitis;
• Diffuse posterior uveitis and choroiditis;
• Optic neuritis;
• Sympathetic ophthalmia;
• Anterior segment inflammation;
• Allergic conjunctivitis;
• Keratitis;
• Allergic marginal corneal ulcer.

Gastrointestinal diseases: to manage critical periods in:

• Ulcerative colitis (systemic therapy);
• Crohn’s disease (systemic therapy).

Respiratory diseases:

• Symptomatic sarcoidosis;
• Berylliosis;
• Focal or disseminated pulmonary tuberculosis (in combination with appropriate antituberculosis chemotherapy);
• Löffler’s syndrome refractory to other treatments;
• Aspiration pneumonitis.

Hematologic diseases:

• Acquired (autoimmune) hemolytic anemia;
• Idiopathic thrombocytopenic purpura in adults (intravenous administration only; intramuscular administration is contraindicated);
• Secondary thrombocytopenia in adults;
• Erythroblastopenia (erythrocytic anemia);
• Congenital (erythroid) hypoplastic anemia.

Oncologic diseases:

• Palliative treatment of leukemia and lymphoma in adults;
• Acute leukemia in children.

Conditions associated with edema:

• Stimulation of diuresis or reduction of proteinuria in idiopathic nephrotic syndrome (without uremia) and renal dysfunction associated with systemic lupus erythematosus.

Diagnostic testing of adrenal function.

Cerebral edema:

• Cerebral edema due to primary or metastatic brain tumors, craniotomy, or head trauma.

The use of dexamethasone for cerebral edema does not replace appropriate neurosurgical evaluation and definitive interventions such as neurosurgical procedures or other specific therapies.

Coronavirus disease 2019 (COVID-19):

• Treatment of coronavirus disease 2019 (COVID-19) in adults and adolescent patients (aged 12 years and older with body weight ≥40 kg) who require supplemental oxygen therapy.

Other indications:

• Tuberculous meningitis with subarachnoid block or risk of block (in combination with appropriate antituberculosis therapy);
• Trichinosis with neurological symptoms or myocardial involvement.

Indications for intra-articular or soft tissue injection: as adjunctive therapy for short-term use (to manage acute episodes or flares) in:

• Rheumatoid arthritis (severe inflammation of a single joint);
• Synovitis associated with osteoarthritis;
• Acute and subacute bursitis;
• Acute gouty arthritis;
• Epicondylitis;
• Acute nonspecific tenosynovitis;
• Post-traumatic osteoarthritis.

Local injection (injection at the site of lesion):

• Keloid lesions;
• Localized hypertrophic, inflammatory, and infiltrated lesions in herpes zoster, psoriasis, and granuloma annulare;
• Discoid lupus erythematosus;
• Lipoid (lipoidic) atrophic dermatitis of Oppenheim;
• Localized alopecia.

May also be used for cystic tumors of aponeurosis or tendons (ganglia).

Contraindications. Intramuscular injection is contraindicated in patients with severe coagulation disorders. Local injection is contraindicated in the presence of bacteremia, systemic fungal infections, unstable joints, or local site infections, including septic arthritis due to gonorrhea or tuberculosis.

Hypersensitivity to dexamethasone or to any other ingredient of the preparation.

Acute viral, bacterial, or systemic fungal infections (unless appropriate therapy is administered), Cushing's syndrome, live vaccine administration.

Interaction with other medicinal products and other forms of interactions. Concomitant use of dexamethasone and nonsteroidal anti-inflammatory drugs increases the risk of gastrointestinal bleeding and ulcer formation.

The effect of dexamethasone is reduced when used concurrently 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 such cases, the dose of dexamethasone should be increased. Interaction between dexamethasone and all the above-mentioned drugs may distort the dexamethasone suppression test results. This should be considered when interpreting test outcomes.

Concomitant use of dexamethasone and drugs that inhibit CYP 3A4 enzyme activity (ketoconazole, macrolides) may increase 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, leading to reduced serum concentrations.

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

By inhibiting CYP 3A4 enzyme activity, ketoconazole may increase serum concentrations of dexamethasone. Conversely, ketoconazole may suppress adrenal synthesis of glucocorticoids, potentially leading to adrenal insufficiency due to reduced dexamethasone concentrations.

Dexamethasone reduces the therapeutic effect of drugs used to treat diabetes mellitus, hypertension, praziquantel, and natriuretic agents (thus, doses of these drugs may need to be increased); however, it enhances the activity of heparin, albendazole, and potassium-wasting diuretics (doses of these drugs may need to be reduced if necessary).

Dexamethasone may alter the effect of coumarin anticoagulants; therefore, prothrombin time should be monitored more frequently when these drugs are used together.

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

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 use 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, making it sometimes difficult to achieve therapeutic serum salicylate concentrations. Caution is required in patients being gradually tapered off corticosteroids, as serum salicylate concentrations may rise, potentially leading to salicylate toxicity.

Concomitant use of oral contraceptives may prolong the half-life of glucocorticoids, enhancing their biological effects and increasing the risk of adverse effects.

Concomitant use of ritodrine and dexamethasone is contraindicated during labor, as it may lead to fatal pulmonary edema in the mother. Fatal outcomes have been reported due to this condition.

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.

Special precautions for use.

In patients who have been treated with dexamethasone for a prolonged period, discontinuation of treatment may result in a 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 often seizures. Therefore, the dose of dexamethasone should be gradually reduced. Abrupt discontinuation may be fatal.

Rarely, hypersensitivity reactions may occur during parenteral corticosteroid therapy; therefore, appropriate precautions should be taken before initiating dexamethasone treatment, considering the possibility of allergic reactions (especially in patients with a history of allergic reactions to any other drugs).

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 treatment, hydrocortisone or cortisone should be used.

If patients have received prolonged dexamethasone therapy and experience severe stress after stopping treatment, dexamethasone therapy should be reinstated, as adrenal insufficiency induced by dexamethasone may persist for several months after discontinuation.

Severe psychiatric reactions may accompany systemic corticosteroid use. Symptoms usually appear within several days or weeks after starting treatment. The risk of these symptoms increases with high-dose therapy. Most reactions resolve upon dose reduction or discontinuation of the drug. Close monitoring and timely detection of psychiatric changes, especially depressive mood, suicidal thoughts, and intentions, are essential. Corticosteroids should be used with particular caution in patients with a history of affective disorders, especially those with a history of allergic reactions to any other medications or in their close relatives. Adverse 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.

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 amebiasis, and pulmonary tuberculosis.

Patients with active pulmonary tuberculosis should receive dexamethasone (in combination with anti-tuberculosis agents) only in rapidly progressive or widely disseminated forms of tuberculosis. Patients with inactive pulmonary tuberculosis who are treated with 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 monitoring is required during the first weeks after myocardial infarction, in patients with thromboembolism, severe myasthenia gravis, glaucoma, hypothyroidism, psychosis or psychoneurosis, and elderly patients.

During treatment, worsening of diabetes or transition from latent to clinical diabetes may occur.

Serum potassium levels should be monitored during prolonged treatment.

Vaccination with live vaccines is contraindicated during dexamethasone treatment. Vaccination with inactivated viral or bacterial vaccines may not elicit the expected antibody production and protective effect. Dexamethasone should generally not be administered within 8 weeks before vaccination or initiated earlier than 2 weeks after vaccination.

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

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

Systemic corticosteroids should not be discontinued in patients already receiving (oral) corticosteroids for other reasons (e.g., patients with chronic obstructive pulmonary disease) who do not require additional oxygen.

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

Intra-articular administration of dexamethasone may lead to local and systemic effects. Frequent use may cause cartilage damage or bone necrosis.

Before intra-articular injection, synovial fluid should be aspirated from the joint and examined (to check for infection). Corticosteroids should not be injected into infected joints. If joint infection develops after injection, appropriate antibiotic therapy should be initiated.

Patients should be advised to avoid physical stress on affected joints until inflammation resolves.

Injection into unstable joints should be avoided.

Corticosteroids may distort the results of skin allergy tests.

Hypertrophic cardiomyopathy has been reported in preterm infants following systemic administration of corticosteroids, including dexamethasone. Most reported cases were reversible after discontinuation of treatment. In preterm infants receiving systemic dexamethasone, diagnostic evaluation and monitoring of cardiac function and structure are recommended.

Pheochromocytoma crisis.

Pheochromocytoma crisis, which may lead to fatal outcomes, has been reported after systemic corticosteroid therapy. Corticosteroids should be administered to patients with suspected or diagnosed pheochromocytoma only after appropriate benefit-risk assessment.

Special information about certain excipients.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., practically sodium-free.

The presence of methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216) in the formulation may cause allergic reactions (possibly delayed), and in individual cases, bronchospasm.

Use during pregnancy or breastfeeding. Harmful effects on the fetus and newborn infant cannot be excluded. The drug suppresses fetal development in utero. Dexamethasone may be prescribed to pregnant women only in rare emergency cases when the expected benefit to the mother outweighs the potential risk to the fetus. Particular caution is recommended in preeclampsia. According to general guidelines for glucocorticoid therapy during pregnancy, the lowest effective dose should be used to control the underlying disease. 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, prednisolone, so high concentrations of dexamethasone may be observed in fetal serum. Some data suggest that even pharmacological doses of glucocorticoids may increase the risk of placental insufficiency, oligohydramnios, delayed fetal development or intrauterine death, elevated white blood cell count (neutrophils) in the fetus, and adrenal insufficiency. There is no evidence confirming teratogenic effects of glucocorticosteroids.

Studies have shown an increased risk of neonatal hypoglycemia after prenatal short-term use of corticosteroids, including dexamethasone, in women at risk of late preterm delivery.

Additional doses of glucocorticoids are recommended during delivery 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.

Lactation. Use during breastfeeding is contraindicated (except in emergency cases). A small amount of glucocorticoids passes into breast milk; therefore, breastfeeding is not recommended for mothers treated with dexamethasone, especially when used above physiological levels (approximately 1 mg). This may lead to impaired growth in the infant and reduced secretion of endogenous corticosteroids.

Ability to affect reaction speed when driving or operating machinery. Dexamethasone does not affect the ability to drive or operate machinery.

Method of administration and dosage. To be administered to adults and children from the neonatal period. Administered intravenously (as injection or infusion), intramuscularly, or locally—via intra-articular injection or injection into the affected skin area or soft tissue infiltrate.

For intravenous infusion, use 0.9% sodium chloride solution or 5% glucose solution as diluent.

Solutions intended for intravenous infusion or further dilution of the drug must not contain preservatives if administered to infants, especially preterm infants.

When the drug is mixed with an infusion solution, aseptic techniques must be followed. Since infusion solutions generally do not contain preservatives, mixtures should be used within 24 hours.

Parenteral preparations should be visually inspected for particulate matter and discoloration immediately before administration to determine solution and container suitability.

The dose should be individually determined based on the patient's specific condition, expected treatment duration, corticosteroid tolerance, and individual response.

Intravenous and intramuscular administration

The recommended initial dose ranges from 0.5 to 9 mg per day, depending on the diagnosis. In milder cases, a dose below 0.5 mg may be sufficient, while in severe conditions, a dose exceeding 9 mg per day may be required.

Initial doses of dexamethasone should be administered until a clinical response is achieved, then the dose should be gradually reduced to the lowest clinically effective level. If high doses are administered for more than several days, the dose should then be gradually tapered over 5–7 days or longer.

If no satisfactory clinical response occurs after an appropriate period, dexamethasone phosphate injections should be discontinued and alternative treatment initiated.

Symptoms requiring dose adjustment should be carefully monitored, including changes in clinical status due to remission or exacerbation of disease, individual response to the drug, and stress effects (e.g., surgery, infection, trauma). Dose may need to be temporarily increased during stress.

If administration must be discontinued after more than 2–3 days of treatment, withdrawal should be gradual.

Intravenous dosing is usually equivalent to oral dosing. However, in certain acute, life-threatening situations, doses exceeding usual levels may be justified and combined with oral dosing. Note that absorption after intramuscular injection is slower.

Shock

In current medical practice, high (pharmacological) doses of corticosteroids are used to treat shock resistant to conventional therapy. The following dexamethasone phosphate injection regimens are used:

• 3 mg/kg body weight over 24 hours by continuous intravenous infusion after an initial intravenous bolus of 20 mg.
• 2–6 mg/kg body weight as a single intravenous injection.
• Initial 40 mg, followed by repeated intravenous injections every 4–6 hours while shock symptoms persist.
• Initial 40 mg, followed by repeated intravenous injections every 2–6 hours while shock symptoms persist.
• 1 mg/kg body weight as a single intravenous injection.

High-dose corticosteroid therapy should continue only until patient stabilization and usually not longer than 48–72 hours.

Cerebral edema

Dexamethasone injection solution is usually administered at an initial dose of 10 mg intravenously, followed by 4 mg intramuscularly every 6 hours until symptoms resolve.

Response to treatment is usually observed within 12–24 hours. Dosage may be reduced after 2–4 days of treatment. The drug should be discontinued gradually over 5–7 days. For palliative use in patients with recurrent or inoperable brain tumors, maintenance therapy at a dose of 2 mg 2–3 times daily may be effective.

Severe allergic conditions

For acute allergic conditions that resolve spontaneously or severe exacerbations of chronic allergic diseases, the following dosing regimen combining parenteral and oral therapy is recommended:

Dexamethasone injection solution, 4 mg/mL: Day 1 – 1 or 2 mL (4 or 8 mg), intramuscularly.

Dexamethasone tablets, 0.5 mg: Days 2 and 3 – 6 tablets in two divided doses daily; Day 4 – 3 tablets in two divided doses; Days 5 and 6 – 1.5 tablets daily; Day 7 – no treatment; Day 8 – follow-up visit.

This regimen is designed to ensure adequate treatment during exacerbation episodes, reducing the risk of overdosing in chronic cases.

COVID-19 treatment

Adults and children aged 12 years and older with body weight ≥40 kg: 6 mg dexamethasone intravenously once daily for up to 10 days.

Treatment duration is individually determined based on the patient's clinical condition.

Elderly patients, patients with renal or hepatic impairment. Dose adjustment is not required.

Local administration

Intra-articular, intralesional, or soft tissue injection is usually used when involvement is limited to one or two joints (areas). Dose and frequency depend on the condition and site of injection. Usual dose: 0.2–6 mg. Repeat intra-articular injection may be performed after 3–4 months. Up to three or four injections may be given into one joint during a lifetime, and no more than two joints should be injected simultaneously. Frequent intra-articular injections may damage joint cartilage and cause bone necrosis.

Intra-articular corticosteroid injection may lead to systemic effects in addition to local effects.

Intra-articular corticosteroid injection into infected joints should be avoided.

Corticosteroids should not be injected into unstable joints.

Some typical single doses are listed below:

Dexamethasone, solution for injection, is particularly recommended for use in combination with one of the less soluble long-acting steroids for intra-articular and soft tissue administration.

Pediatric doses

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

For all other indications, the initial dose range is 0.02–0.3 mg/kg/day given in 3–4 injections (0.6–9 mg/m² body surface area/day).

For comparison, the equivalent milligram doses of various corticosteroids are listed below.

A dose of 0.75 mg of dexamethasone is equivalent to 2 mg of paramethasone, or 4 mg of methylprednisolone and triamcinolone, or 5 mg of prednisone and prednisolone, or 20 mg of hydrocortisone, or 25 mg of cortisone, or 0.75 mg of betamethasone.

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

Children. Should be used in neonates only when absolutely necessary. Careful monitoring of growth and development in children and adolescents is required during treatment with dexamethasone.

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

Overdose usually occurs only after several weeks of administration. Overdose may cause most of the adverse effects listed in the section "Side effects," particularly Cushing's syndrome. There is no specific antidote. Management of overdose should be supportive and symptomatic. Hemodialysis is not an effective method for enhancing the elimination of dexamethasone from the body.

Adverse Reactions.

Adverse effects during short-term dexamethasone therapy:

Immune system disorders: Hypersensitivity reactions.

Endocrine system disorders: Transient suppression of adrenal gland function.

Nutrition and metabolism disorders: Decreased carbohydrate tolerance, increased appetite, weight gain, hypertriglyceridemia.

Psychiatric disorders: Psychiatric disturbances.

Gastrointestinal disorders: Peptic ulcer, acute pancreatitis.

Adverse effects during long-term dexamethasone therapy:

Immine system disorders: Reduced immune response and increased susceptibility to infections.

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

Nutrition and metabolism disorders: Obesity.

Eye disorders: Cataract, glaucoma.

Vascular disorders: Hypertension; telangiectasia.

Skin and subcutaneous tissue disorders: Skin thinning.

Musculoskeletal and connective tissue disorders: Muscle atrophy, osteoporosis, aseptic bone necrosis, long bone fractures.

Adverse effects that may also occur in individual organs and systems during dexamethasone therapy:

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

Immune system disorders: 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, hypertrophic cardiomyopathy in premature infants.

Vascular disorders: Hypertensive encephalopathy.

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

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

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

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

Nutrition and metabolism disorders: Transition from latent to clinical diabetes; increased insulin and oral antidiabetic drug requirements in diabetic patients; sodium and water retention; increased potassium loss; hypokalemic alkalosis; negative nitrogen balance due to protein catabolism; hypocalcemia.

Gastrointestinal disorders: Dyspepsia, vomiting, nausea, hiccup, peptic ulcer of the stomach or duodenum, 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), vertebral compression fractures, tendon ruptures (especially when used concomitantly with certain quinolones), joint cartilage damage and bone necrosis (with frequent intra-articular injections).

Skin and subcutaneous tissue disorders: 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.

Reproductive system and breast disorders: 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, atrophy of the skin and subcutaneous tissue, sterile abscess, skin redness.

Signs 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 death. In some cases, withdrawal symptoms may resemble 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 at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Incompatibilities. The product should not be mixed with other medicinal products except 0.9% sodium chloride solution or 5% glucose solution.

Precipitation occurs when dexamethasone is mixed with chlorpromazine, diphenhydramine, doxapram, doxorubicin, daunorubicin, idarubicin, hydromorphone, ondansetron, prochlorperazine, potassium nitrate, and vancomycin.

Approximately 16% of dexamethasone degrades in a solution of 2.5% glucose and 0.9% sodium chloride with amikacin.

Some medicinal products, such as lorazepam, should be mixed with dexamethasone in glass vials, not in plastic bags (lorazepam concentration drops below 90% within 3–4 hours when stored in polyvinyl chloride bags at room temperature).

Some medicinal products, such as metaraminol, exhibit so-called "delayed incompatibility" — developing over 24 hours when mixed with dexamethasone.

Dexamethasone with glycopyrrolate: The pH of the residual solution is 6.4, which is outside the stability range.

Packaging. 1 ml or 2 ml in ampoules, packs of 5, 10 in a carton; 5 in a blister pack in a carton.

Prescription status. Prescription only.

Manufacturer.

Limited Liability Company "Research Plant 'GNCLS'".

LIMITED LIABILITY COMPANY "CORPORATION 'ZDOROVIYA'".

Manufacturer's name and address of place of business.

Ukraine, 61057, Kharkiv region, city of Kharkiv, Vorobiova Street, 8.

(Limited Liability Company "Research Plant 'GNCLS')

Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, 22.

(LIMITED LIABILITY COMPANY "CORPORATION 'ZDOROVIYA')