The hormonal agent shows antiallergic, anti-inflammatory and immunosuppressive activity. Injections are prescribed for antitoxic, desensitizing, antishock therapy. Due to the active components, the susceptibility of adrenergic receptors to endogenous catecholamines increases.
Composition and release form
Tablets - 1 tablet:
- Active ingredient: Dexamethasone – 0.0005 g
- Excipients: potato starch – 0.0340 g; sucrose (sugar) – 0.1140 g; stearic acid – 0.0015 g.
Tablets weighing 0.15 g.
Tablets 0.5 mg.
10, 14 tablets in a blister pack made of polyvinyl chloride film and aluminum foil.
5, 10 blister packs of 10 tablets each or 4 blister packs of 14 tablets each with instructions for use in a cardboard pack.
Description of the dosage form
Tablets are white, flat-cylindrical with a chamfer.
Pharmacokinetics
Absorption
After oral administration, it is quickly and completely absorbed, the maximum concentration of dexamethasone in the blood plasma is 1-2 hours.
Distribution
In the blood it binds (60–70%) to a specific carrier protein – transcortin. Easily passes through histohematic barriers (including the blood-brain and placental barriers).
Metabolism
Metabolized in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites.
Removal
Excreted by the kidneys (a small amount of dexamethasone passes into breast milk). Half-life is 3-5 hours.
Pharmacodynamics
Dexamethasone is a synthetic glucocorticosteroid (GCS), a methylated derivative of fluoroprednisolone. It has anti-inflammatory, antiallergic, desensitizing, immunosuppressive, antishock and antitoxic effects.
Inhibits the secretion of thyroid-stimulating hormone and follicle-stimulating hormone.
Increases the excitability of the central nervous system, reduces the number of lymphocytes and eosinophils, increases the number of red blood cells (stimulates the production of erythropoietin). Interacts with specific cytoplasmic receptors and forms a complex that penetrates the cell nucleus, stimulates the synthesis of matrix ribonucleic acid (mRNA); the latter induces the formation of proteins, including lipocortin, that mediate cellular effects. Lipocortin inhibits phospholipase A2, suppresses the release of arachidonic acid and suppresses the synthesis of endoperoxides, prostaglandins, leukotrienes, which contribute to inflammation, allergies and others.
Effect on protein metabolism: reduces the amount of protein in plasma (due to globulins) with an increase in the albumin/globulin ratio, increases albumin synthesis in the liver and kidneys; enhances protein catabolism in muscle tissue.
Effect on lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (fat accumulation mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.
Effect on carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract (GIT); increases the activity of glucose-6-phosphatase, leading to an increase in the flow of glucose from the liver into the blood; increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases, which leads to the activation of gluconeogenesis.
Effect on water-electrolyte metabolism: retains sodium ions and water in the body, stimulates the excretion of potassium ions (mineralocorticosteroid activity), reduces the absorption of calcium ions from the gastrointestinal tract, “washes out” calcium ions from the bones, increases the excretion of calcium ions by the kidneys.
The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils; inducing the formation of lipocortins and reducing the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes and organelle membranes (especially lysosomal ones).
The antiallergic effect develops as a result of suppression of the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, a decrease in the number of circulating basophils, suppression of the development of lymphoid and connective tissue, a decrease in the number of T and B lymphocytes, mast cells, reducing the sensitivity of effector cells to allergy mediators, suppressing antibody formation, changing the body's immune response.
In chronic obstructive pulmonary disease, the effect is based mainly on inhibition of inflammatory processes, inhibition of development or prevention of swelling of the mucous membranes, inhibition of eosinophilic infiltration of the submucosal layer of the bronchial epithelium, deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucous membrane. Increases the sensitivity of beta-adrenergic receptors of small and medium-caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of bronchial secretions due to inhibition or reduction of its production.
Antishock and antitoxic effects are associated with an increase in blood pressure (due to an increase in the concentration of circulating catecholamines and restoration of the sensitivity of adrenergic receptors to them, as well as vasoconstriction), a decrease in the permeability of the vascular wall, membrane protective properties, and activation of liver enzymes involved in the metabolism of endo- and xenobiotics.
The immunosuppressive effect is due to inhibition of the release of cytokines (interleukin-1, interleukin-2; interferon gamma) from lymphocytes and macrophages. Suppresses the synthesis and secretion of adrenocorticotropic hormone (ACTH), and secondarily the synthesis of endogenous GCS.
The peculiarity of the action is significant inhibition of pituitary function and the almost complete absence of mineralocorticosteroid activity. Doses of 1-1.5 mg/day inhibit the adrenal cortex; biological half-life is 32-72 hours (duration of inhibition of the hypothalamic-pituitary-adrenal cortex system).
In terms of the strength of glucocorticoid activity, 0.5 mg of dexamethasone corresponds to approximately 3.5 mg of prednisolone, 15 mg of hydrocortisone or 17.5 mg of cortisone for oral dosage forms.
Indications for use of Dexamethasone
Systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, periarteritis nodosa, dermatomyositis, rheumatoid arthritis).
Acute and chronic inflammatory diseases of the joints: gouty and psoriatic arthritis, osteoarthritis (including post-traumatic), polyarthritis, glenohumeral periarthritis, ankylosing spondylitis (ankylosing spondylitis), juvenile arthritis, syndrome
Stilla in adults, bursitis, nonspecific tenosynovitis, synovitis and epicondylitis.
Rheumatic fever, acute rheumatic carditis.
Acute and chronic allergic diseases: allergic reactions to drugs and foods, serum sickness, urticaria, allergic rhinitis, angioedema, drug exanthema, hay fever.
Skin diseases: pemphigus, psoriasis, eczema, atopic dermatitis, diffuse neurodermatitis, contact dermatitis (affecting a large surface of the skin), toxicerma, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell's syndrome), bullous dermatitis herpetiformis, malignant exudative erythema (syndrome) Stevens-Johnson).
Brain edema (only after confirmation of symptoms of increased intracranial pressure by magnetic resonance or computed tomography) caused by a brain tumor and/or associated with surgery or radiation injury.
Allergic eye diseases: allergic corneal ulcers, allergic forms of conjunctivitis.
Inflammatory eye diseases: sympathetic ophthalmia, severe sluggish anterior and posterior uveitis, optic neuritis.
Primary or secondary adrenal insufficiency (including the condition after removal of the adrenal glands).
Congenital adrenal hyperplasia.
Kidney diseases of autoimmune origin (including acute glomerulonephritis); nephrotic syndrome.
Subacute thyroiditis.
Diseases of the hematopoietic organs - agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lymphoid and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital (erythroid) hypoplastic anemia.
Lung diseases: acute alveolitis, pulmonary fibrosis, stage II-III sarcoidosis. Bronchial asthma (for bronchial asthma, the drug is prescribed only in severe cases, ineffectiveness or inability to take inhaled corticosteroids).
Tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy).
Berylliosis, Loeffler's syndrome (not amenable to other therapy).
Lung cancer (in combination with cytostatics).
Multiple sclerosis.
Gastrointestinal diseases: ulcerative colitis, Crohn's disease, local enteritis.
Hepatitis.
Prevention of transplant rejection as part of complex therapy.
Hypercalcemia due to cancer, nausea and vomiting during cytostatic therapy.
Multiple myeloma.
Conducting a test for the differential diagnosis of hyperplasia (hyperfunction) and tumors of the adrenal cortex.
Contraindications to the use of Dexamethasone
- For short-term use for “life-saving” indications, the only contraindication is hypersensitivity; systemic mycosis;
- simultaneous use of live and attenuated vaccines with immunosuppressive doses of the drug;
- sucrose intolerance, isomaltase/sucrase deficiency, glucose-galactose malabsorption; breastfeeding period; children up to 3 years old.
Carefully:
Parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently suffered, including recent contact with a patient) –
- herpes simplex, herpes zoster (viremic phase), chicken pox, measles;
- amebiasis, strongyloidiasis (established or suspected);
- active and latent tuberculosis.
Use of Dexamethasone during pregnancy and children
Dexamethasone crosses the placenta (can reach high concentrations in the fetus) and into breast milk. During pregnancy, especially in the first trimester, or in women planning pregnancy, the use of Dexamethasone is indicated only if the expected therapeutic effect outweighs the risk of negative effects on the mother or fetus. GCS should be prescribed during pregnancy only for absolute indications. With long-term therapy during pregnancy, the possibility of fetal damage cannot be excluded. If used in the third trimester of pregnancy, there is a risk of atrophy of the adrenal cortex in the fetus, which may require replacement therapy in the newborn. If it is necessary to carry out treatment with the drug during breastfeeding, breastfeeding should be stopped.
Breakthrough from the past
Effective: 35 regions will receive the first batches of Avifavir
Deliveries will be made in two weeks
Immunosuppressants, which include the anti-inflammatory drug dexamethasone, can help fight severe coronavirus infection. As Oleg Batishchev, deputy director for scientific work at the Institute of Physics and Chemistry of the Russian Academy of Sciences, told Izvestia, this remedy helps with complications caused by overactivity of the immune system (the so-called cytokine storm).
— As far as I know, quite a lot of drugs were tested that were supposed to help combat the development of this path of the disease. “All of them have existed for a long time, and they were used in the treatment of a number of other, mainly autoimmune, pathologies,” the scientist said. “The fact that dexamethasone showed its effectiveness is certainly an important finding. I hope this will help treat severe forms of COVID-19.
Researchers at the University of Oxford previously announced breakthrough results. A report on their website suggests that inexpensive and long-established dexamethasone reduces mortality in hospitalized patients with severe respiratory complications of COVID-19. British infectious disease specialists conducted a randomized trial in which 2,104 patients received 6 mg of this drug once a day (in tablet form or intravenously) for ten days.
Photo: tass/dpa/Marcel Kusch
The results were so impressive that WHO immediately reported them. This is despite the fact that the study itself has not yet been published. The WHO Director General called the data on the effectiveness of dexamethasone a “scientific breakthrough.” According to him, the anti-inflammatory drug reduces the risk of death of patients with COVID-19 connected to ventilators by 35%. And among patients receiving oxygen - by 20%.
Izvestia Help
Dexamethasone has been widely used since the 1980s. This is a medicine from the group of glucocorticosteroids, which has a pronounced anti-inflammatory, antiallergic, decongestant and immunosuppressive (suppressing immunity) effect on the body. The product is of synthetic origin; in fact, it is an analogue of a person’s own hormones secreted by the adrenal glands. It suppresses the functions of tissue macrophages and also limits the migration of leukocytes to the area of inflammation. As experts emphasize, the use of this drug is dangerous, since all steroids have a large number of serious side effects.
Side effects of Dexamethasone
The incidence and severity of side effects depend on the duration of use, the size of the dose used and the ability to comply with the circadian rhythm of the prescription. Dexamethasone is usually well tolerated. It has low mineralocorticoid activity, that is, its effect on water and electrolyte metabolism is small. As a rule, low and medium doses of dexamethasone do not cause sodium and water retention in the body or increased potassium excretion.
- Endocrine system disorders: decreased glucose tolerance, “steroidal” diabetes mellitus or manifestation of latent diabetes mellitus, suppressed adrenal function, Itsenko-Cushing syndrome (moon face, pituitary type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae), delayed sexual development in children.
- Blood and lymphatic system disorders: moderate leukocytosis, leukocyturia, lymphopenia, eosinopenia, polycythemia.
- Gastrointestinal tract disorders: nausea, vomiting, abdominal pain, discomfort in the epigastric region, pancreatitis, “steroid” gastric and duodenal ulcers, erosive esophagitis, bleeding and perforation of the stomach and intestinal wall, increased or decreased appetite , flatulence, hiccups. In rare cases, increased activity of liver transaminases and alkaline phosphatase.
- Disorders of the heart and blood vessels: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or progression of CHF, electrocardiographic changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis and thromboembolism, vasculitis, increased capillary fragility. In patients with acute and subacute myocardial infarction, the necrosis focus spreads, the formation of scar tissue slows down, which can lead to rupture of the heart muscle.
- Nervous system disorders: increased intracranial pressure, cerebellar pseudotumor, headache, convulsions.
- Mental disorders: nervousness or anxiety, insomnia, emotional lability, delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, suicidal tendencies.
- Visual disorders: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral eye infections, trophic changes in the cornea, exophthalmos, corneal perforation, central serous chorioretinopathy.
- Hearing and labyrinthine disorders: dizziness, vertigo.
- Metabolic and nutritional disorders: hypercholesterolemia, increased excretion of calcium ions, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating, epidural lipomatosis. Caused by mineralocorticosteroid activity - fluid and sodium ion retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).
- Disorders of the musculoskeletal and connective tissue: slowing of growth and ossification processes in children (premature closure of the epiphyseal growth plates), osteoporosis (very rarely - pathological bone fractures, aseptic necrosis of the head of the humerus and femur), rupture of muscle tendons, "steroid" myopathy, decreased muscle mass (atrophy).
- Disorders of the skin and subcutaneous tissues: delayed healing of wounds, petechiae, ecchymoses, thinning of the skin, atrophy of the skin and subcutaneous tissue, hyper- or hypopigmentation, “steroid” acne, stretch marks, a tendency to develop pyoderma and candidiasis, impaired skin pigmentation (hypo- or hyperpigmentation), telangiectasia.
- Immune system disorders: generalized (skin rash, skin itching, anaphylactic shock), local allergic reactions.
- Infectious and parasitic diseases: development or exacerbation of infections (the appearance of this side effect is facilitated by jointly used immunosuppressants and vaccination), masking of infections.
- General disorders and disorders at the injection site: withdrawal syndrome.
What does Dexamethasone help with, indications and contraindications
The drug is a synthetic corticosteroid, an analogue of the hormone of the adrenal cortex. The component composition of the medication helps:
- normalize the functioning of extracellular structures of cartilage and bone tissues;
- reduce the level of capillary permeability;
- stabilize membranes;
- slow down the processes of cytokine release from lymphocytes and macrophages;
- accelerate protein catabolism;
- slow down glucose utilization and calcium absorption;
- retain water and sodium ions in tissues.
The processing of components occurs in the liver, partially in the kidneys and other organs. Metabolic products are excreted through the genitourinary system.
The drug is used against pathologies amenable to systemic therapy, as an addition to the main course of treatment. Intravenous and intramuscular injections are given when tablets or local medications are ineffective.
Dexamethasone is prescribed to patients:
- with allergies and rheumatic diseases;
- swelling of brain tissue;
- shock states of various origins;
- individual kidney lesions;
- autoimmune disorders;
- diseases of the respiratory tract, blood;
- acute severe dermatoses.
The drug is prescribed for hormone replacement therapy and the fight against inflammatory bowel pathologies. Dexamethasone is contraindicated:
- with hypersensitivity to the component composition;
- infectious, parasitic diseases of bacterial and viral origin;
- systemic mycoses, osteoporosis, immunodeficiency;
- myasthenia gravis, ulcers, colitis and other gastrointestinal diseases;
- lesions of the cardiovascular department;
- diabetes mellitus, psychosis, acute renal or liver failure.
The medicine is not injected into the joints if they are unstable, spontaneous bleeding of the apparatus, fractures or infectious lesions. The ban includes periarticular osteoporosis, the postoperative period - after arthroplasty.
Drug interactions
Dexamethasone increases the toxicity of cardiac glycosides (due to the resulting hypokalemia, the risk of developing arrhythmias increases).
Accelerates the elimination of acetylsalicylic acid, reduces its concentration in the blood (when dexamethasone is discontinued, the concentration of salicylates in the blood increases and the risk of side effects increases).
When used simultaneously with live antiviral vaccines and against the background of other types of immunizations, it increases the risk of viral activation and the development of infections.
Increases the metabolism of isoniazid, mexiletine (especially in “fast acetylators”), which leads to a decrease in their plasma concentrations.
Increases the risk of developing the hepatotoxic effect of paracetamol (induction of “liver” enzymes and the formation of a toxic metabolite of paracetamol).
Increases (with long-term therapy) the content of folic acid.
Hypokalemia caused by GCS can increase the severity and duration of muscle blockade due to muscle relaxants.
In high doses, it reduces the effect of somatropin.
Antacids reduce the absorption of corticosteroids.
Dexamethasone reduces the effect of hypoglycemic drugs; enhances the anticoagulant effect of coumarin derivatives.
Weakens the effect of vitamin D on the absorption of calcium ions in the intestinal lumen.
Ergocalciferol and parathyroid hormone prevent the development of osteopathy caused by GCS.
Reduces the concentration of praziquantel in the blood.
Cyclosporine (inhibits metabolism) and ketoconazole (reduces clearance) increase toxicity.
Thiazide diuretics, carbonic anhydrase inhibitors, other corticosteroids and amphotericin B increase the risk of hypokalemia, sodium-containing drugs - edema and increased blood pressure.
Non-steroidal anti-inflammatory drugs and ethanol increase the risk of developing ulceration of the gastrointestinal mucosa and bleeding; in combination with non-steroidal anti-inflammatory drugs for the treatment of arthritis, it is possible to reduce the dose of GCS due to the summation of the therapeutic effect.
Indomethacin, displacing dexamethasone from its association with albumin, increases the risk of developing its side effects.
Amphotericin B and carbonic anhydrase inhibitors increase the risk of osteoporosis.
The therapeutic effect of GCS is reduced under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of “liver” microsomal enzymes (increased metabolic rate).
Mitotane and other inhibitors of adrenal function may necessitate an increase in the dose of GCS.
The clearance of GCS increases against the background of thyroid hormones.
Immunosuppressants increase the risk of developing infections and lymphoma or other lymphoproliferative disorders associated with Epstein-Barr virus.
Estrogens (including oral estrogen-containing contraceptives) reduce the clearance of corticosteroids, prolong the half-life and their therapeutic and toxic effects.
The appearance of hirsutism and acne is facilitated by the simultaneous use of other steroid hormonal drugs - androgens, estrogens, anabolic steroids, oral contraceptives.
Tricyclic antidepressants may increase the severity of depression caused by taking dexamethasone (not indicated for the treatment of these side effects).
The risk of developing cataracts increases when used in conjunction with other corticosteroids, antipsychotic drugs (neuroleptics), carbutamide and azathioprine.
Simultaneous administration with m-anticholinergics (including antihistamines, tricyclic antidepressants), nitrates contributes to the development of increased intraocular pressure.
When used simultaneously with fluoroquinolones, the risk of tendonopathy (mainly Achilles tendon) increases in elderly patients and in patients with tendon diseases.
Antimalarials (chloroquine, hydroxychloroquine, mefloquine) in combination with dexamethasone may increase the risk of developing myopathy and cardiomyopathy.
Angiotensin-converting enzyme inhibitors, when administered concomitantly with dexamethasone, can change the composition of peripheral blood.
Instructions for use DEXAMETHASON solution
Allergic reactions may occur (although rarely) during parenteral use of corticoids. Appropriate measures should be taken before starting treatment, taking into account this possibility (especially in patients with a history of allergic reactions to any drugs).
Patients undergoing long-term treatment with dexamethasone may experience corticoid withdrawal syndrome. Therefore, the dosage of dexamethasone should be gradually reduced.
If during therapy or when discontinuing a drug the patient is exposed to unexpected stress (trauma, surgery or serious illness), then the dose of dexamethasone should be increased or hydrocortisone or cortisone prescribed. In patients who have experienced severe stress after discontinuation of long-term dexamethasone, dexamethasone should be restarted as induced adrenal insufficiency may persist for several months after discontinuation of treatment.
Treatment with dexamethasone or natural glucocorticoids may mask signs of existing or new infection and signs of interstitial perforation.
Dexamethasone can aggravate the course of systemic fungal infections, latent amebiasis and pulmonary tuberculosis.
In patients with active pulmonary tuberculosis, dexamethasone should be prescribed (in combination with antituberculosis therapy) in cases of fulminant or severe disseminated pulmonary tuberculosis. Patients with inactive tuberculosis who are taking dexamethasone or patients with a positive tuberculin test should receive chemoprophylaxis.
Particular caution and close medical monitoring should be performed in patients with osteoporosis, hypertension, heart failure, tuberculosis, glaucoma, liver failure, renal failure, diabetes, active gastric and duodenal ulcers, recent intestinal anastomosis, ulcerative colitis and epilepsy. Particular attention should be paid to patients in the first weeks after myocardial infarction, as well as patients with thromboembolism, asthenic bulbar palsy, glaucoma, hypothyroidism, psychosis or psychoneurosis, and elderly patients.
During treatment with dexamethasone, an exacerbation of diabetes or a transition from a latent form to the form of clinical manifestations of diabetes may occur.
During long-term treatment, it is necessary to monitor serum potassium levels. Vaccination with live vaccines is contraindicated during treatment with dexamethasone. Immunization with killed viral or bacterial vaccines does not lead to the expected increase in antibodies and does not have the expected protective effect. Dexamethasone is usually not prescribed 8 weeks before and 2 weeks after vaccination. Patients receiving or taking high doses of dexamethasone for a long time should avoid contact with people with measles; In case of accidental contact, prophylactic treatment with immunoglobulin is recommended. Caution is advised in patients recovering from recent surgery and a bone fracture, as dexamethasone may delay the healing of wounds and fractures.
The effect of glucocorticoids is potentiated in patients with liver cirrhosis or hypothyroidism. Intra-articular administration of corticoids can cause local and systemic effects. Frequent use may cause damage to articular cartilage and bone necrosis.
Before intra-articular injection, synovial fluid should be evacuated from the joint and examined (for possible infection). Injecting corticosteroids into infected joints should be avoided. If septic inflammation of the joint develops after the injection, then appropriate antibacterial treatment must be started.
Patients should be informed that it is necessary to avoid putting stress on the joints into which the injection was performed until the inflammatory process has completely resolved.
Injections into unstable joints are not recommended. Corticosteroids may interfere with allergy skin test results. Dexamethasone is used in children and adolescents only under strict indications. During treatment with dexamethasone, the growth and development of children and adolescents should be carefully monitored.
Special information about some of the ingredients of the drug.
This drug contains less than 1 mmol (23 mg) sodium per dose, which is a negligible amount.
Pregnancy and lactation.
Dexamethasone should be prescribed to pregnant women only in selected urgent cases when the expected benefit to the mother justifies the risk to the fetus.
Particular care should be taken in case of preeclampsia. According to general recommendations for glucocorticoid treatment during pregnancy, the lowest effective dose to control the underlying disease should be used.
Glucocorticoids are excreted in small quantities in breast milk. Therefore, breastfeeding is not recommended for mothers taking dexamethasone, especially when using high physiological doses (about 1 mg). This can lead to fetal growth retardation and decreased secretion of endogenous corticosteroids.
Impact on the ability to drive a car or use other machinery.
Dexamethasone does not affect the ability to drive a car or operate machinery.
Dexamethasone dosage
Orally, in individually selected doses, the amount of which is determined by the type of disease, the degree of its activity and the nature of the patient’s response.
The average daily dose is 0.75-9 mg. In severe cases, large doses can be used, divided into 3-4 doses. The maximum daily dose is usually 15 mg. After achieving a therapeutic effect, the dose is gradually reduced (usually by 0.5 mg every 3 days) to a maintenance dose of 2-4.5 mg/day. The minimum effective dose is 0.5-1 mg/day.
Children (depending on age) are prescribed 83.3-333.3 mcg/kg or 2.5-10 mg/sq.m/day in 3-4 doses.
The duration of dexamethasone use depends on the nature of the pathological process and the effectiveness of treatment and ranges from several days to several months or more. Treatment is stopped gradually (at the end several injections of corticotropin are prescribed).
For bronchial asthma, rheumatoid arthritis, ulcerative colitis – 1.5-3 mg/day; for systemic lupus erythematosus – 2-4.5 mg/day; for oncohematological diseases – 7.5-10 mg.
For the treatment of acute allergic diseases, it is advisable to combine parenteral and oral administration: 1 day – 4-8 mg parenterally; Day 2 – orally, 4 mg 3 times a day; 3, 4 days – orally, 4 mg 2 times a day; 5, 6 days – 4 mg/day, orally; Day 7 – drug withdrawal.
Dexamethasone test (Liddle test). It is carried out in the form of small and large tests. For a small test, dexamethasone is given to the patient 0.5 mg every 6 hours during the day (that is, at 8 a.m., 2 p.m., 8 p.m., and 2 a.m.). Urine for the determination of 17-hydroxycorticosteroids or free cortisol is collected from 8 a.m. to 8 a.m. 2 days before the administration of dexamethasone and also 2 days at the same time intervals after taking the indicated doses of dexamethasone. These doses of dexamethasone inhibit the formation of corticosteroids in almost all apparently healthy individuals. 6 hours after the last dose of dexamethasone, plasma cortisol levels are below 135-138 nmol/l (less than 4.5-5 mcg/100 ml). Reducing the excretion of 17-hydroxycorticosteroids below 3 mg/day, and free cortisol below 54-55 nmol/day (below 19-20 mcg/day) excludes hyperfunction of the adrenal cortex. In persons suffering from Cushing's disease or syndrome, no changes in the secretion of corticosteroids are observed during a small test.
When conducting a large test, dexamethasone is prescribed 2 mg every 6 hours for 2 days (that is, 8 mg dexamethasone per day). Urine is also collected to determine 17-hydroxycorticosteroids or free cortisol (if necessary, determine free cortisol in plasma). With Itsenko-Cushing's disease, there is a decrease in the excretion of 17-hydroxycorticosteroids or free cortisol by 50% or more, while with adrenal tumors or adrenocorticotropic-ectopic (or corticoliberin-ectopic) syndrome, the excretion of corticosteroids does not change. In some patients with adrenocorticotropic-ectopic syndrome, a decrease in the excretion of corticosteroids is not detected even after taking dexamethasone at a dose of 32 mg/day.
Dexamethasone withdrawal
Adrenal cortical atrophy develops with long-term therapy and may persist for many years after cessation of treatment.
Therefore, withdrawal of corticosteroids after long-term therapy should always be gradual to avoid acute adrenal insufficiency and tapered over weeks or months depending on the dose and duration of treatment.
For patients taking corticosteroids in doses above physiological doses (approximately 1 mg dexamethasone) for more than 3 weeks, discontinuation should not be abrupt. The method of dose reduction largely depends on the likelihood of disease relapse. Upon discontinuation, clinical assessment of disease activity may be required. If relapse of the disease is unlikely when systemic corticosteroids are discontinued, but there is concern about suppression of the hypothalamic-pituitary-adrenal (HPA) axis, the dose of systemic corticosteroids can be reduced sharply to achieve physiological values. After reaching a daily dose of 1 mg of dexamethasone, a slow dose reduction is necessary until the hypothalamic-pituitary-adrenal axis is completely restored. Abrupt discontinuation of systemic corticosteroid treatment, for up to 3 weeks, is appropriate if disease relapse is unlikely. A sudden reduction in the daily dose of dexamethasone after 3 weeks of therapy to 6 mg is unlikely to lead to significant suppression of the hypothalamic-pituitary-adrenal axis in most patients.
In the following groups of patients, gradual withdrawal of systemic glucocorticoid therapy is strictly indicated even after a 3-week therapeutic course:
- Patients who have received repeated courses of systemic corticosteroids, especially if taken for more than 3 weeks.
- When this course is prescribed during the first year after stopping a long course (months or years) of glucocorticoid treatment.
- Patients predisposed to adrenal insufficiency except for therapy with exogenous corticosteroids.
- Patients taking dexamethasone at a dose exceeding 6 mg/day.
- Patients taking repeated doses in the evening.
With long-term glucocorticoid therapy, any intercurrent illness, injury or surgery requires a temporary increase in dosage; If corticosteroids have been stopped shortly before, they may need to be reintroduced temporarily.
Anti-inflammatory/immunosuppressive effects and infection
Suppression of the immune response and immune function during systemic glucocorticoid therapy increases the body's susceptibility to infections. The clinical picture of diseases can be distorted and the course of such serious infections as septicopyemia and tuberculosis can be masked and recognized only at a fairly critical stage.
In some cases, for example, with tuberculosis, viral and fungal eye diseases, it is necessary to combine glucocorticoid therapy with antibacterial therapy.
Particular attention should be paid to chickenpox. Chickenpox disease can be fatal in immunosuppressed patients. Therefore, patients (as well as parents of small children) who have not previously had chickenpox are strictly recommended to avoid contact with patients with chickenpox or herpes zoster, and if this cannot be avoided, they must immediately come under strict medical control. Unimmunized but exposed patients on glucocorticoid therapy or who have been on glucocorticoid therapy within the previous 3 months receive passive immunization with herpes zoster immunoglobulin. Immunization must be carried out within 10 days after exposure. If a patient is diagnosed with chickenpox, strict medical monitoring and immediate therapeutic measures are necessary. Treatment with glucocorticoids should not be stopped, and the dose should be increased if necessary.
Measles
Patients should avoid contact with people with measles, and if this happens, they should immediately consult a doctor and undergo preventive immunization by intramuscular injection of immunoglobulin.
Live vaccines should not be used if the immune response is suppressed. The immune response to other vaccines may also be weakened.
Impaired visual perception
Visual disturbances may occur with the use of systemic and local corticosteroids. If a patient exhibits symptoms such as blurred vision or other visual disturbances, consider referring the patient to an ophthalmologist to evaluate possible causes, which may include cataracts, glaucoma, or a rare condition such as central serous chorioretinopathy (CSCR). These data have been reported following the use of systemic and topical corticosteroids.
Special Precautions
Patients with the following conditions who plan to initiate systemic glucocorticoid therapy should take special precautions and be under close medical supervision.
- Osteoporosis (at a special risk group for postmenopausal women).
- Hypertension or chronic heart failure.
- A history of acute affective disorders (in particular, steroid psychosis)
- Diabetes mellitus (or family history)
- History of tuberculosis, since glucocorticoids may contribute to its reactivation
- Glaucoma (or family history)
- Liver failure
- Kidney failure
- Epilepsy
- Ulcers of the gastrointestinal tract
- Migraine
- Some parasitic infestations, in particular amoebiasis
- With prolonged use of glucocorticoids, a slowdown in growth and ossification processes in children may be observed (premature closure of the epiphyseal growth zones)
- Cushing's syndrome.
Injections into the space between the tendon sheath and the tendon when treating tendinitis or tenosynovitis should be done with caution, because cases of tendon rupture have been reported in practice.
Use in pediatrics
Glucocorticoids can cause dose-dependent, irreversible growth retardation in infants, children, and adolescents.
Dexamethasone is used to treat and prevent chronic lung disease in premature infants (unlicensed use). Recent studies have suggested an association between the use of dexamethasone in premature infants and the development of cerebral palsy. In this regard, an individual approach to prescribing the drug is necessary, taking into account the risk/benefit assessment.
Use in old age
Common side effects of systemic corticosteroids may be associated with more serious consequences in older age.
Such patients should be under direct medical supervision to prevent the development of life-threatening conditions.
See Section 4.5 (Drug Summary) for information about interactions with other medications.
Dexamethasone contains sodium
This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. Contains virtually no sodium.
Dexamethasone contains methylparaben and propylparaben
The drug contains methylparaben and propylparaben, which can cause allergic reactions (delayed) and in rare cases, bronchospasm.
Dexamethasone contains metabisulfite
Sodium metabisulfite may rarely cause severe hypersensitivity reactions and bronchospasm.
OVERDOSE
Corticosteroid overdose is difficult to determine because the therapeutic dose will vary depending on the indications and requirements of the patient. With pulsed intravenous administration of massive doses of glucocorticoids, the likelihood of side effects is relatively reduced.
Increased corticosteroid-related side effects may occur. Treatment is symptomatic and, if necessary, supportive.
STORAGE CONDITIONS
Store out of the reach of children at a temperature not exceeding 25ºC in the original packaging.
Shelf life – 3 years. Do not use Dexamethasone after the expiration date indicated on the drug package. When indicating the expiration date, we mean the last day of the specified month. Do not use the drug if damage is found on the ampoule.
Your doctor or pharmacist is responsible for storing Dexamethasone. They are also responsible for ensuring that unused medication is properly disposed of.