Dexamethasone, tablets 0.5 mg 56 pcs

Dexamethasone is a synthetic glucocorticosteroid (GCS), methylated fluoroprednisolone derivative. It has anti-inflammatory, anti-allergic, desensitizing, immunosuppressive, antishock and antitoxic effects.

Inhibits secretion of thyroid hormone and follicle stimulating hormone.

Increases central nervous system excitability, decreases the number of lymphocytes and eosinophils, increases the number of erythrocytes (stimulates erythropoietin production).

Interacts with specific cytoplasmic receptors and forms a complex penetrating into cell nucleus, stimulates synthesis of matrix ribonucleic acid (mRNA); the latter induces formation of proteins, including lipocortin, mediating cellular effects. Lipocortin inhibits phospholipase A2, inhibits the release of arachidonic acid and inhibits the synthesis of endoperoxins, prostaglandins, leukotrienes, contributing to the processes of inflammation, allergy and others.

Effect on protein metabolism: reduces the amount of protein in the plasma (at the expense of globulins) with an increase in albumin/globulin ratio, increases the synthesis of albumin in the liver and kidneys; increases 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 hypercholesterolemia.

Effect on carbohydrate metabolism: increases absorption of carbohydrates from the gastrointestinal tract (GIT), increases the activity of glucose-6-phosphatase, leading to increased glucose flow from the liver into the blood, increases the activity of phosphoenolpyruvate carboxylase and aminotransferase synthesis, which leads to activation of gluconeogenesis.

Effect on water-electrolyte metabolism: it retains sodium ions and water in the body, stimulates excretion of potassium ions (mineralocorticosteroid activity), reduces the absorption of calcium ions from the GIT, “washes” calcium ions from the bones, increases excretion of calcium ions by kidneys.

Anti-inflammatory activity is associated with inhibition of eosinophils release of inflammatory mediators, induction of lipocortin formation and reduction of hyaluronic acid-producing mast cells number, capillary permeability reduction, stabilization of cell and organelle membranes (especially lysosomal).

. An antiallergic effect is produced due to suppression of allergy mediators synthesis and secretion, inhibition of histamine and other bioactive substances release from sensitized mast cells and basophils, reduction of circulating basophils number, suppression of lymphoid and connective tissue development, reduction of T- and B-lymphocytes quantity, mast cells, reduction of effector cells sensitivity to allergy mediators, suppression of antibody formation, change in the organism immune response.

In chronic obstructive pulmonary disease action is mainly based on inhibition of inflammatory processes, inhibition or prevention of mucous membrane edema, inhibition of eosinophilic infiltration of submucous layer of bronchial epithelium, deposition of circulating immune complexes in bronchial mucosa, and inhibition of mucous membrane erosion and desquamation. It increases sensitivity of small and medium caliber bronchial beta-adrenoreceptors to endogenous catecholamines and exogenous sympathomimetics, decreases bronchial secretion viscosity by inhibiting or reducing its production.

Antishock and antitoxic action is associated with increase of arterial pressure (due to increase in concentration of circulating catecholamines and restoration of adrenoreceptors sensitivity to them as well as vasoconstriction), reduction of vascular wall permeability, membrane-protective properties, activation of liver enzymes involved in metabolism of endo- and xenobiotics.

Immunosuppressive effect is caused by inhibition of cytokine release (interleukin-1, interleukin-2, interferon gamma) from lymphocytes and macrophages.

Inhibits the synthesis and secretion of adrenocorticotropic hormone (ACTH), and secondary the synthesis of endogenous GCS.
Peculiarities of action are significant inhibition of pituitary function and almost complete absence of mineralocorticosteroid activity. Doses of 1-1.5 mg/day inhibit adrenal cortex; biological half-life is 32-72 hours (duration of inhibition of hypothalamic-pituitary-adrenal cortical layer system).

In terms 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.

Pharmacokinetics

Absorption

After oral administration is quickly and completely absorbed, the maximum concentration of dexamethasone in blood plasma is 1-2 hours.

Distribution

In the blood it is bound (60 – 70%) with the specific carrier protein – transcortin. Easily passes through histohematic barriers (including the blood-brain barrier and the placental barrier).

Metabolism

Metabolized in liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites.

Excretion

Excreted by the kidneys (a small amount of dexamethasone penetrates into breast milk). The elimination half-life is 3-5 hours.

Indications

• Systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, periarteritis nodosa, dermatomyositis, rheumatoid arthritis).
• Acute and chronic inflammatory joint diseases: gouty and psoriatic arthritis, osteoarthritis (including post-traumatic), polyarthritis, periarthritis of the shoulder, ankylosing spondylitis (Behterev’s disease), juvenile arthritis, Still’s syndrome in adults, bursitis, non-specific tenosynovitis, synovitis and epicondylitis.
• Rheumatic fever, acute rheumocarditis.
• Acute and chronic allergic diseases: allergic reactions to drugs and food, serum sickness, urticaria, allergic rhinitis, angioedema, drug exanthema, pollinosis.
• Skin diseases: Vesicles, psoriasis, eczema, atopic dermatitis, diffuse neurodermatitis, contact dermatitis (with large skin surface affected), toxiderma, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell syndrome), bullous herpetiform dermatitis, malignant exudative erythema (Stevens-Johnson syndrome).
• Cerebral edema (only after confirming the symptoms of increased intracranial pressure by MRI or CT scan) due to a brain tumor and/or associated with surgery or radiation damage.
• Allergic eye diseases: allergic corneal ulcers, allergic forms of conjunctivitis.
• Inflammatory eye diseases: sympathetic ophthalmia, severe flaccid anterior and posterior uveitis, optic neuritis.
• Primary or secondary adrenal insufficiency (including conditions after adrenal removal).
• Congenital adrenal hyperplasia.
• Kidney diseases of autoimmune genesis (including acute glomerulonephritis); nephrotic syndrome.
• Acute thyroiditis.
• .Diseases of the hematopoietic organs – agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lympho- and myeloid leukemia, lymphogranulematosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital (erythroid) hypoplastic anemia.
• Lung diseases: acute alveolitis, pulmonary fibrosis, sarcoidosis stage II-III. Bronchial asthma (in bronchial asthma, the drug is indicated only with a severe course, ineffectiveness or inability to take inhaled GCS).
• Tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy).
• Berylliosis, Leffler syndrome (not amenable to other therapy).
• Lung cancer (in combination with cytostatics).
• Rassociated sclerosis.
• Gastrointestinal diseases: ulcerative colitis, Crohn’s disease, local enteritis.
• Hepatitis.
• Prevention of transplant rejection reaction as part of comprehensive therapy.
• Hypercalcemia in cancer, nausea and vomiting during cytostatic therapy.
• Myeloma disease.
• Testing in the differential diagnosis of hyperplasia (hyperfunction) and tumors of the adrenal cortex.
  

Active ingredient

Dexamethasone

Composition

Active ingredient:

Dexamethasone – 0,0005 g,

Excipients: to obtain tablets weighing 0.15 g

potato starch – 0.0340 g,

sucrose (sugar) – 0.1140 g,

stearic acid – 0.0015 g.

How to take, the dosage

Orally, in individually adjusted doses, the size of which is determined by the type of disease, the degree of its activity and the nature of the patient’s response.

Average daily dose is 0.75-9 mg. In severe cases larger doses divided into 3-4 doses may be used. The maximum daily dose is usually 15 mg. After a therapeutic effect is achieved, 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 intakes.
Duration of dexamethasone administration depends on the nature of the pathological process and efficiency of treatment and varies from several days to several months or more. The treatment is discontinued gradually (at the end several injections of corticotropin are prescribed).

In bronchial asthma, rheumatoid arthritis, ulcerative colitis – 1.5-3 mg/day; in systemic lupus erythematosus – 2-4.5 mg/day; in oncohematological diseases – 7.5-10 mg.

For treatment of acute allergic diseases it is reasonable to combine parenteral and oral administration: 1 day – 4-8 mg parenterally; 2 day – orally, 4 mg 3 times a day; 3, 4 days – orally, 4 mg 2 times a day; 5, 6 days – 4 mg/day, orally; 7 day – drug withdrawal.

Dexamethasone test (Liddle test). It is carried out in the form of small and large tests. In the small test, the patient is given 0.5 mg of dexamethasone every 6 hours during the day (that is, at 8 a.m., 2 p.m., 8 p.m., and 2 a.m.).

Urine for determination of 17-oxycorticosteroids 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 the specified dexamethasone doses. These doses of dexamethasone inhibit corticosteroid formation in almost all nearly healthy individuals. Six hours after the last dose of dexamethasone, plasma cortisol levels are below 135-138 nmol/L (less than 4.5-5 µg/100 mL).

Decreases in 17-oxycorticosteroid excretion below 3 mg/d and free cortisol below 54-55 nmol/d (below 19-20 µg/d) exclude adrenal cortex hyperfunction. No change in corticosteroid secretion is noted in individuals with Icenko-Cushing’s disease or syndrome in the small test.
In the large test, dexamethasone is administered 2 mg every 6 hours for 2 days (that is, 8 mg of dexamethasone per day).

Urine is also collected for determination of 17-oxycorticosteroids or free cortisol (free plasma cortisol is determined if necessary). In Icenko-Cushing’s disease, there is a decrease in 17-oxycorticosteroid or free cortisol excretion of 50% or more, whereas in adrenal tumors or adrenocorticotropic-ectopic (or corticoliberin-ectopic) syndrome, corticosteroid excretion is unchanged.

In some patients with adrenocorticotropic-ectopic syndrome there is no decrease in corticosteroid excretion even after administration of dexamethasone at a dose of 32 mg/day.

Interaction

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

Accelerates excretion of acetylsalicylic acid, reduces its concentration in the blood (when canceling dexamethasone 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, increases the risk of virus activation and 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 hepatotoxic effects of paracetamol (induction of “hepatic” enzymes and formation of the toxic metabolite of paracetamol).

Increases (during prolonged therapy) folic acid.

Hypokalemia caused by GCS may increase the severity and duration of muscle block against the background of muscle relaxants.

In high doses it reduces the effect of somatropin.

Antacids reduce absorption of GCS agents.

Dexamethasone reduces the effect of hypoglycemic drugs; increases the anticoagulant effect of coumarin derivatives.

Weakens the effect of vitamin D on absorption of calcium ions in the intestinal lumen. Ergocalciferol and parathormone prevent the development of GCS-induced osteopathy.

Reduces the blood concentration of praziquantel.

Cyclosporine (inhibits metabolism) and ketoconazole (reduces clearance) increase toxicity.

Thiazide diuretics, carbohydrase inhibitors, other GCS 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 gastrointestinal mucosal ulceration, bleeding, in combination with non-steroidal anti-inflammatory drugs for the treatment of arthritis, the dose of GCS may be reduced due to the totalization of therapeutic effect.

Indomethacin, displacing dexamethasone from binding to albumin, increases the risk of its side effects.
Amphotericin B and carboanhydrase inhibitors increase the risk of osteoporosis.

Therapeutic effect of GCS is decreased under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of “hepatic” microsomal enzymes (increased metabolic rate).
Mitotane and other inhibitors of adrenal cortex function may require increasing the GCS dose.

GCS clearance is increased with thyroid hormones.

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

Estrogens (including oral estrogen-containing contraceptives) decrease GCS clearance, prolong the elimination half-life and their therapeutic and toxic effects.

The occurrence of hirsutism and acne is promoted by the simultaneous use of other steroid hormone medications – androgens, estrogens, anabolic steroids, oral contraceptives.
Tricyclic antidepressants may increase the severity of depression caused by taking dexamethasone (not indicated for therapy of these side effects).

The risk of cataracts increases when used against other GCS, antipsychotic drugs (neuroleptics), carbutamide and azathioprine.

Simultaneous use with m-cholinoblockers (including antihistamines, tricyclic antidepressants) and nitrates increases intraocular pressure.
Simultaneous use with fluoroquinolones increases the risk of tendopathy (mainly Achilles tendon) in elderly patients and in patients with tendon diseases.

Antimalarials (chloroquine, hydroxychloroquine, mefloquine) in combination with dexamethasone may increase the risk of myopathy, cardiomyopathy.

Angiotensin-converting enzyme inhibitors in combination with dexamethasone may alter peripheral blood composition.

Special Instructions

When prescribing dexamethasone for intercurrent infections, septic conditions and tuberculosis, specific antibacterial therapy should be carried out simultaneously when using the drug in patients with latent tuberculosis, lymphadenitis after BCG vaccination, polio, acute and chronic bacterial, parasitic infections; specific therapy in patients with gastric and/or intestinal ulcer disease, osteoporosis.

Daily use develops atrophy of the adrenal cortex by 5 months of treatment.

Can mask some symptoms of infections; immunization is useless during treatment.
Sudden withdrawal of GCS, especially in case of previous high-dose use, results in GCS “withdrawal” syndrome (not due to hypocorticism): decreased appetite, nausea, lethargy, generalized muscular-skeletal pain, asthenia, and acute adrenal insufficiency may also occur (decreased blood pressure, arrhythmia, sweating, weakness, oligoanuria, vomiting, abdominal pain, diarrhea, hallucinations, fainting, coma).

After withdrawal, relative insufficiency of the adrenal cortex persists for several months. If stressful situations occur during this period, GCS is prescribed (as indicated) for the time, if necessary in combination with mineralocorticosteroids.

The dose of dexamethasone should be temporarily increased in stressful situations during therapy (surgery, trauma). Temporary increase in the dose of the drug in stressful situations is necessary both before and after the stress.

In children during long-term treatment it is necessary to monitor carefully the dynamics of growth and development. Children who have been in contact with patients with measles or chickenpox during treatment are preventively prescribed specific immunoglobulins.

During treatment with dexamethasone (especially long-term) it is necessary to monitor ophthalmologist, control blood pressure and water-electrolyte balance, as well as peripheral blood picture and blood glucose concentration. In order to reduce side effects, anabolic steroids, antacids can be prescribed, and the intake of potassium ions can be increased (eating foods rich in potassium and calcium, or taking potassium, calcium, and vitamin D preparations). The food should be rich in proteins, vitamins, low in fat, carbohydrates and salt.

In children during the growth phase GCS should be used only with absolute indications and under close supervision of the attending physician.

When dexamethasone is used there is a risk of severe anaphylactic reactions, bradycardia.
Against the background of the drug therapy the risk of strongyloidiasis activation increases.

During the drug therapy the patients with CHF, uncontrolled arterial hypertension, corneal trauma and ulcers, glaucoma should be closely monitored.
Myasthenia gravis course may worsen.

Sperm motility may be decreased during the use of GCS.

Administration of the preparation may mask the symptoms of “peritoneal irritation” in patients with perforation of the stomach or intestinal wall.

The action of the drug is increased in patients with liver cirrhosis. It should be noted that in patients with hypothyroidism clearance of dexamethasone decreases, and in patients with thyrotoxicosis – increases.
In patients with diabetes mellitus blood glucose concentrations should be monitored and if necessary the doses of hypoglycemic drugs should be adjusted.

Effect on the ability to drive vehicles and mechanisms

Given the possible side effects during therapy with Dexamethasone, caution should be exercised when driving vehicles and operating machinery, engaging in other activities that require increased concentration and rapid psychomotor reactions.

Contraindications

For short-term use for “vital” indications the only contraindication is hypersensitivity; systemic mycosis; simultaneous use of live and weakened vaccines with immunosuppressive doses of the drug;
sucrose intolerance, isomaltase/saccharase deficiency, glucose-galactose malabsorption; breastfeeding period; children under 3 years old.

With caution

Parasitic and infectious diseases of viral, fungal or bacterial nature (current or recent, including recent contact with a patient) – herpes simplex, herpes zoster (viremic phase), varicella, measles; amebiasis, strongyloidiasis (established or suspected); active and latent tuberculosis. Severe infectious diseases may only be treated against the background of specific antimicrobial therapy.
Pre- and post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination. Immunodeficiency conditions (including acquired immunodeficiency syndrome or human immunodeficiency virus (HIV infection).

Gastrointestinal diseases: peptic ulcer, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with risk of perforation or abscesses, diverticulitis.

Cardiovascular diseases, including recently myocardial infarction (patients with acute and subacute myocardial infarction may have disseminated necrosis, delayed scar tissue formation and rupture of the heart muscle as a result), decompensated chronic heart failure (CHF), arterial hypertension, hyperlipidemia.

Endocrine diseases – diabetes (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Icenko-Cushing’s disease, obesity (III-IV stage).
Severe chronic renal and/or hepatic insufficiency, nephrourolithiasis.

Hypoalbuminemia and conditions predisposing to its occurrence.

Systemic osteoporosis, myasthenia gravis, acute psychosis, poliomyelitis (except for bulbar encephalitis form), open- and closed-angle glaucoma.

Use of the drug in elderly patients (due to the high risk of osteoporosis and arterial hypertension).

Acute psychosis, severe affective disorders (including in anamnesis).

Eye infection caused by herpes simplex virus (due to the risk of corneal perforation).

Pregnancy.

In children during the growth phase GCS should be used only on absolute indications and under close supervision of the attending physician.

Side effects

The frequency and severity of side effects depend on the duration of use, the size of the dose used, and the ability to observe the circadian rhythm of administration. Usually dexamethasone is well tolerated.

It has low mineralocorticoid activity, that is, its effect on water-electrolyte metabolism is small. As a rule, low and medium doses of dexamethasone do not cause sodium and water retention in the body, increased potassium excretion.

The following side effects have been described:

Endocrine disorders: reduced glucose tolerance, “steroidal” diabetes mellitus or manifestation of latent diabetes mellitus, depression of adrenal function, Icenko-Cushing’s syndrome (moon-shaped face, pituitary-type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, stretch marks), delayed sexual development in children.

Blood and lymphatic system disorders: moderate leukocytosis, leukocyturia, lymphopenia, eosinopenia, polycythemia.

Gastrointestinal disorders: nausea, vomiting, abdominal pain, discomfort in epigastric region, pancreatitis, “steroid” gastric and 12 duodenal ulcer, 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.

Cardiovascular disorders: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or progression of CHF, electrocardiographic changes characteristic of hypokalemia, increased arterial pressure, hypercoagulation, thrombosis and thromboembolism, vasculitis, increased capillary fragility. In patients with acute and subacute myocardial infarction – expansion of necrosis, delayed formation of scar tissue, which may lead to rupture of the heart muscle.

Nervous system disorders: increased intracranial pressure, pseudotumor cerebellar, headache, seizures.

Mental disorders: nervousness or anxiety, insomnia, emotional lability, delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, suicidal tendencies.

Eye disorders: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, tendency to develop secondary bacterial, fungal or viral eye infections, trophic changes of cornea, exophthalmos, corneal perforation, central serous chorioretinopathy.

Hearing and labyrinth 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.

Mineralocorticosteroid-associated – fluid and sodium ion retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

Musculoskeletal and connective tissue disorders: growth retardation and ossification processes in children (premature closure of 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, decrease of muscle mass (atrophy).

Skin and subcutaneous tissue disorders: delayed wound healing, petechiae, ecchymoses, skin thinning, skin and subcutaneous tissue atrophy, hyper- or hypopigmentation, “steroid” acne, stretch marks, tendency to pyoderma and candidiasis development, skin pigmentation disorders (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 (appearance of this side effect is promoted by jointly used immunosuppressants and vaccination), masking infections.

General disorders and disorders of the injection site: “withdrawal” syndrome.

Overdose

Dose-dependent side effects may increase, with the exception of allergic reactions. The dose of dexamethasone should be reduced.

Treatment: symptomatic.

Pregnancy use

Dexamethasone penetrates through the placenta (may reach high concentrations in the fetus) and into the 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 exceeds the risk of adverse effects on the mother or fetus. GCS should be administered during pregnancy only for absolute indications.

During prolonged therapy during pregnancy the possibility of fetal impairment cannot be excluded. In case of application during the third trimester of pregnancy there is a risk of adrenal cortex atrophy in a fetus, which may require substitution therapy in a newborn.

If it is necessary to treat with the drug during breastfeeding, breastfeeding should be stopped.

Similarities

Oftan Dexamethasone, Maxidex, Dexamethasone-Vial, Dexamethasone, Megadexan