Detametazon (Solution) Instructions for Use

Marketing Authorization Holder

Dalkhimpharm, JSC (Russia)

ATC Code

H02AB02 (Dexamethasone)

Active Substance

Dexamethasone (Rec.INN registered by WHO)

Dosage Form

Detametazon

Injection solution 4 mg/1 ml: amp. 5, 10, or 25 pcs.

Dosage Form, Packaging, and Composition

1 ml – dark glass ampoules (5) – cardboard packs.
1 ml – dark glass ampoules (10) – cardboard packs.
1 ml – dark glass ampoules (25) – cardboard packs.

Clinical-Pharmacological Group

Injectable corticosteroids

Pharmacotherapeutic Group

Glucocorticosteroid

Pharmacological Action

Glucocorticosteroid (GCS). It suppresses the functions of leukocytes and tissue macrophages. It limits the migration of leukocytes to the area of inflammation. It impairs the ability of macrophages to phagocytose and to form interleukin-1. It promotes the stabilization of lysosomal membranes, thereby reducing the concentration of proteolytic enzymes in the area of inflammation. It reduces capillary permeability caused by the release of histamine. It suppresses fibroblast activity and collagen formation.

It inhibits the activity of phospholipase A₂, which leads to the suppression of prostaglandin and leukotriene synthesis. It suppresses the release of COX (mainly COX-2), which also contributes to the reduction of prostaglandin production.

It reduces the number of circulating lymphocytes (T- and B-cells), monocytes, eosinophils, and basophils due to their movement from the vascular bed into the lymphoid tissue; it suppresses antibody formation.

Dexamethasone suppresses the release of ACTH and β-lipotropin by the pituitary gland but does not reduce the level of circulating β-endorphin. It inhibits the secretion of TSH and FSH.

When applied directly to blood vessels, it exerts a vasoconstrictor effect.

Dexamethasone has a pronounced dose-dependent effect on the metabolism of carbohydrates, proteins, and fats. It stimulates gluconeogenesis, promotes the uptake of amino acids by the liver and kidneys, and increases the activity of gluconeogenesis enzymes. In the liver, Dexamethasone enhances glycogen storage by stimulating the activity of glycogen synthase and the synthesis of glucose from protein metabolism products. The increase in blood glucose levels stimulates insulin secretion.

Dexamethasone suppresses glucose uptake by fat cells, which leads to the activation of lipolysis. However, due to increased insulin secretion, lipogenesis is stimulated, leading to fat accumulation.

It has a catabolic effect in lymphoid and connective tissue, muscles, adipose tissue, skin, and bone tissue. Osteoporosis and Cushing’s syndrome are the main factors limiting long-term GCS therapy. As a result of the catabolic effect, growth suppression in children is possible.

In high doses, Dexamethasone can increase the excitability of brain tissues and contribute to a lowering of the seizure threshold. It stimulates excessive production of hydrochloric acid and pepsin in the stomach, which contributes to the development of peptic ulcer.

When used systemically, the therapeutic activity of dexamethasone is due to its anti-inflammatory, antiallergic, immunosuppressive, and antiproliferative effects.

Pharmacokinetics

Plasma protein binding is 60-70%. It crosses histohematic barriers. It is excreted in small amounts in breast milk.

It is metabolized in the liver.

The elimination half-life (T_1/2) is 2-3 hours. It is excreted by the kidneys.

Indications

Shock of various origins; cerebral edema (in brain tumor, traumatic brain injury, neurosurgical intervention, cerebral hemorrhage, encephalitis, meningitis, radiation injury); status asthmaticus; severe allergic reactions (angioedema, bronchospasm, dermatosis, acute anaphylactic reaction to drugs, serum transfusion, pyrogenic reactions); acute hemolytic anemias, thrombocytopenia, acute lymphoblastic leukemia, agranulocytosis; severe infectious diseases (in combination with antibiotics); acute adrenal cortical insufficiency; acute croup; joint diseases (scapulohumeral periarthritis, epicondylitis, styloiditis, bursitis, tenosynovitis, compression neuropathy, osteochondrosis, arthritis of various etiologies, osteoarthritis).

ICD codes

Dosage Regimen

Individual. For parenteral administration, it is administered intravenously slowly as a bolus or by infusion (in acute and emergency conditions); intramuscularly; periarticular and intra-articular administration is also possible. From 4 to 20 mg of dexamethasone can be administered 3-4 times per day. The duration of parenteral use is usually 3-4 days, after which maintenance therapy with the oral form is initiated. In the acute period of various diseases and at the beginning of treatment, Dexamethasone is used in higher doses. After achieving the effect, the dose is reduced at intervals of several days until the maintenance dose is reached or until treatment is discontinued.

Adverse Reactions

From the endocrine system: decreased glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, suppression of adrenal function, Cushing’s syndrome (including moon face, pituitary-type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia, striae), delayed sexual development in children.

From the metabolism: increased excretion of calcium ions, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating, hypernatremia, hypokalemia.

From the nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor cerebri, headache, convulsions.

From the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of chronic heart failure, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction – spread of the necrosis focus, slowing of scar tissue formation, which can lead to rupture of the heart muscle; with intracranial administration – nosebleed.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, gastrointestinal bleeding and perforation, increased or decreased appetite, flatulence, hiccups; rarely – increased activity of liver transaminases and alkaline phosphatase.

From the organ of vision: 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 the cornea, exophthalmos.

From the musculoskeletal system: slowing of growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rarely – pathological bone fractures, aseptic necrosis of the humeral and femoral head), muscle tendon rupture, steroid myopathy, decrease in muscle mass (atrophy).

Dermatological reactions: delayed wound healing, petechiae, ecchymoses, thinning of the skin, hyper- or hypopigmentation, steroid acne, striae, tendency to develop pyoderma and candidiasis.

Allergic reactions: skin rash, skin itching, anaphylactic shock.

Effects associated with immunosuppressive action: development or exacerbation of infections (the appearance of this side effect is facilitated by concurrently used immunosuppressants and vaccination).

Local reactions: tissue necrosis.

Contraindications

For short-term use for vital indications – hypersensitivity to dexamethasone.

For intra-articular injection and injection directly into the lesion site: previous arthroplasty, pathological bleeding (endogenous or caused by the use of anticoagulants), intra-articular bone fracture, infectious (septic) inflammatory process in the joint and periarticular infections (including in the anamnesis), as well as general infectious disease, severe periarticular osteoporosis, absence of signs of inflammation in the joint (“dry” joint, for example, in osteoarthritis without synovitis), severe bone destruction and joint deformity (sharp narrowing of the joint space, ankylosis), joint instability as a result of arthritis, aseptic necrosis of the epiphyses forming the joint.

Use in Pregnancy and Lactation

During pregnancy (especially in the first trimester), as well as during breastfeeding, Dexamethasone is used taking into account the expected therapeutic effect and the negative impact on the fetus. With long-term therapy during pregnancy, the possibility of impaired fetal growth cannot be ruled out. If used at the end of pregnancy, there is a risk of adrenal cortex atrophy in the fetus, which may require replacement therapy in the newborn.

Use in Hepatic Impairment

Should be used with caution in severe chronic liver failure.

Use in Renal Impairment

Should be used with caution in severe chronic renal failure.

Pediatric Use

Can be used in children for vital indications.

Geriatric Use

Can be used for vital indications.

Special Precautions

Should be used with caution in parasitic and infectious diseases of viral, fungal or bacterial nature (current or recently suffered, including recent contact with a patient) – herpes simplex, herpes zoster (viremic phase), chickenpox, measles, amebiasis, strongyloidiasis (established or suspected), systemic mycosis; active and latent tuberculosis. Use in severe infectious diseases is permissible only against the background of specific therapy.

Should be used with caution within 8 weeks before and 2 weeks after vaccination, with lymphadenitis after BCG vaccination, with immunodeficiency conditions (including AIDS or HIV infection).

Should be used with caution in gastrointestinal diseases: gastric and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, recently created intestinal anastomosis, ulcerative colitis with threat of perforation or abscess formation, diverticulitis.

Should be used with caution in diseases of the cardiovascular system, including after a recent myocardial infarction (in patients with acute and subacute myocardial infarction, spread of the necrosis focus, slowing of scar tissue formation and, as a result, rupture of the heart muscle is possible), in decompensated chronic heart failure, arterial hypertension, hyperlipidemia), in endocrine diseases – diabetes mellitus (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Cushing’s disease, in severe chronic renal and/or hepatic failure, nephrourolithiasis, in hypoalbuminemia and conditions predisposing to its occurrence, in systemic osteoporosis, myasthenia gravis, acute psychosis, obesity (grades III-IV), in poliomyelitis (except for the form of bulbar encephalitis), open-angle and closed-angle glaucoma.

If intra-articular administration is necessary, it should be used with caution in patients with a generally severe condition, and in case of ineffectiveness (or short duration) of the action of 2 previous administrations (taking into account the individual properties of the glucocorticosteroids used).

Before starting and during glucocorticosteroid therapy, it is necessary to monitor the complete blood count, blood glucose levels, and plasma electrolyte content.

In case of intercurrent infections, septic conditions, and tuberculosis, antibiotic therapy should be carried out simultaneously.

Dexamethasone-induced relative adrenal insufficiency may persist for several months after its discontinuation. Considering this, during stressful situations occurring in this period, hormone therapy is resumed with the simultaneous administration of salts and/or mineralocorticoids.

With sudden withdrawal of dexamethasone, especially in case of prior use in high doses, a so-called withdrawal syndrome (not caused by hypocorticism) occurs, manifested by anorexia, nausea, lethargy, generalized musculoskeletal pain, and general weakness. After discontinuation of dexamethasone, relative adrenal cortex insufficiency may persist for several months. If stressful situations arise during this period, glucocorticosteroids are prescribed (as indicated) temporarily, if necessary in combination with mineralocorticoids.

During treatment, control of blood pressure, water-electrolyte balance, peripheral blood picture, and blood glucose levels is required, as well as observation by an ophthalmologist.

In children during long-term treatment, careful monitoring of growth and development dynamics is necessary. Children who were in contact with patients with measles or chickenpox during treatment are prophylactically prescribed specific immunoglobulins.

Drug Interactions

When used concomitantly with antipsychotic agents, bucarban, azathioprine, there is a risk of developing cataracts; with agents that have an anticholinergic effect – a risk of developing glaucoma.

When used concomitantly with dexamethasone, the effectiveness of insulin and oral hypoglycemic drugs is reduced.

When used concomitantly with hormonal contraceptives, androgens, estrogens, anabolic steroids, hirsutism and acne are possible.

When used concomitantly with diuretics, increased potassium excretion is possible; with NSAIDs (including acetylsalicylic acid) – the frequency of erosive-ulcerative lesions and gastrointestinal bleeding increases.

When used concomitantly with oral anticoagulants, a weakening of the anticoagulant effect is possible.

When used concomitantly with cardiac glycosides, tolerance to cardiac glycosides may worsen due to potassium deficiency.

When used concomitantly with aminoglutethimide, a reduction or suppression of the effects of dexamethasone is possible; with carbamazepine – a reduction in the action of dexamethasone is possible; with ephedrine – increased excretion of dexamethasone from the body; with imatinib – a possible decrease in the plasma concentration of imatinib due to induction of its metabolism and increased excretion from the body.

When used concomitantly with itraconazole, the effects of dexamethasone are enhanced; with methotrexate – increased hepatotoxicity is possible; with praziquantel – a possible decrease in the blood concentration of praziquantel.

When used concomitantly with rifampicin, phenytoin, barbiturates, a weakening of the effects of dexamethasone is possible due to increased excretion from the body.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.