Celestone (Tablets, Solution) Instructions for Use

ATC Code

H02AB01 (Betamethasone)

Active Substance

Betamethasone (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Corticosteroids for oral administration

Pharmacotherapeutic Group

Glucocorticosteroid

Pharmacological Action

Glucocorticosteroid. Suppresses the functions of leukocytes and tissue macrophages. Limits the migration of leukocytes to the area of inflammation. Impairs the ability of macrophages to phagocytose and to form interleukin-1. Promotes stabilization of lysosomal membranes, thereby reducing the concentration of proteolytic enzymes in the area of inflammation. Reduces capillary permeability caused by the release of histamine. Suppresses fibroblast activity and collagen formation.

Inhibits the activity of phospholipase A₂, leading to suppression of prostaglandin and leukotriene synthesis. Suppresses the release of COX (mainly COX-2), which also contributes to the reduction of prostaglandin production.

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; suppresses antibody formation.

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

When applied directly to blood vessels, it has a vasoconstrictive effect.

Betamethasone has a pronounced dose-dependent effect on the metabolism of carbohydrates, proteins, and fats. Stimulates gluconeogenesis, promotes the uptake of amino acids by the liver and kidneys, and increases the activity of gluconeogenesis enzymes. In the liver, Betamethasone 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.

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

Retains sodium ions and water in the body, stimulates the excretion of potassium ions, reduces calcium absorption from the gastrointestinal tract, leaches calcium ions from bones, and increases calcium excretion by the kidneys.

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 glucocorticosteroid therapy. As a result of the catabolic effect, growth suppression in children is possible.

In high doses, Betamethasone can increase the excitability of brain tissue and contribute to a lowering of the seizure threshold. Stimulates excessive production of hydrochloric acid and pepsin in the stomach, leading to the development of peptic ulcer.

When used systemically, the therapeutic activity of betamethasone is due to its anti-inflammatory, anti-allergic, immunosuppressive, and anti-proliferative action.

When used externally and locally, the therapeutic activity of betamethasone is due to its anti-inflammatory, anti-allergic, and anti-exudative (due to the vasoconstrictive effect) action.

In anti-inflammatory activity, it exceeds hydrocortisone by 30 times and does not possess mineralocorticoid activity. The presence of a fluorine atom in the molecule enhances the anti-inflammatory activity of betamethasone.

Betamethasone in the form of dipropionate is characterized by a prolonged action.

Pharmacokinetics

Plasma protein binding is about 64%, V_d is 84 L. Metabolized in the liver. Metabolites are excreted primarily by the kidneys, a small portion – with bile.

When absorbed through the skin, Betamethasone is characterized by similar pharmacokinetic properties, both with topical and systemic use. Systemic absorption after topical application is 12-14%.

With local and topical application on intact skin, absorption may be insignificant. The presence of an inflammatory process, as well as the use of an occlusive dressing, can increase the extent of absorption.

Indications

For oral administration primary or secondary adrenal cortical insufficiency, congenital adrenal hyperplasia, acute (non-suppurative) and subacute thyroiditis, hypercalcemia due to neoplastic disease, rheumatic diseases, collagen diseases, allergic diseases, symptomatic sarcoidosis, Loeffler’s syndrome, berylliosis, idiopathic or secondary thrombocytopenia in adults, autoimmune hemolytic anemia, erythroblastopenia (erythrocyte anemia), erythroid hypoplastic anemia, transfusion reactions, palliative therapy of leukemia and lymphoma in adults and acute leukemia in children; ulcerative colitis, Bell’s palsy.

For parenteral administration shock (including burn, traumatic, surgical, toxic, cardiogenic, hemotransfusion, anaphylactic); allergic reactions (acute, severe forms), anaphylactoid reactions; cerebral edema (including due to brain tumor or associated with surgery, radiation therapy, or head injury), increased intracranial pressure; bronchial asthma (severe form), status asthmaticus; systemic connective tissue diseases (SLE, rheumatoid arthritis); acute adrenal insufficiency, prevention of adrenal cortical insufficiency in patients who have received glucocorticosteroids for a long time; thyrotoxic crisis; acute hepatitis, hepatic coma; poisoning by caustic fluids; diphtheria croup (in combination with appropriate antimicrobial therapy).

For intra-articular injection rheumatoid arthritis, osteoarthritis, traumatic arthritis, osteochondritis, acute gouty arthritis. Soft tissue diseases (including bursitis, fibrositis, tendinitis, tenosynovitis, myositis).

For external use dermatoses, various types of eczema (including atopic, infantile, nummular), prurigo nodularis of Hyde, simple dermatitis, exfoliative dermatitis, neurodermatitis, solar dermatitis, seborrheic dermatitis, radiation dermatitis, intertrigo, psoriasis (except for extensive plaque psoriasis), cutaneous or anogenital (excluding candidiasis) itching, discoid lupus erythematosus, as an auxiliary agent in the complex therapy of generalized erythroderma.

For local application diseases of the eye and ear with a pronounced allergic or inflammatory component.

ICD codes

Dosage Regimen

Tablets

The dose is set individually.

For oral administration, the daily dose for adults is 0.25-8 mg, for children – 17-250 mcg/kg. After long-term use, withdrawal of betamethasone should be done gradually, reducing the dose by 250 mcg every 2-3 days.

For IV administration (slow bolus or drip), a single dose is 4-8 mg, if necessary it can be increased to 20 mg; the maintenance dose is typically 2-4 mg. A single dose for IM administration is 4-6 mg.

For intra-articular injection and injection directly into the lesion site for soft tissue diseases, depending on the size of the joint and the area of the lesion, a single dose is 0.4-6 mg.

Subconjunctivally, a single dose is 2 mg.

For external use, apply a thin layer to the affected area of skin 2-6 times/day until clinical improvement, then apply 1-2 times/day. When using betamethasone in children, as well as in patients with facial lesions, the course of treatment should not exceed 5 days.

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, fluid retention and sodium ions (peripheral edema), hypernatremia, hypokalemic syndrome (including hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

From the Central Nervous System: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, cerebellar pseudotumor, headache, seizures.

From the Cardiovascular System: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or worsening of chronic heart failure, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thromboses. In patients with acute and subacute myocardial infarction – spread of the necrosis focus, slowed formation of scar tissue, 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. In rare cases – increased activity of hepatic transaminases and alkaline phosphatase.

From the Sensory Organs: sudden loss of vision (with parenteral administration in the head, neck, nasal turbinates, scalp, deposition of betamethasone crystals in the eye vessels is possible), 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: slowed 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, decreased muscle mass (atrophy); with intra-articular injection – increased joint pain.

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: generalized (skin rash, skin itching, anaphylactic shock), local allergic reactions.

Local Reactions with parenteral administration – burning, numbness, pain, paresthesias and infections at the injection site, rarely – necrosis of surrounding tissues, scar formation at the injection site; with intramuscular injection (especially into the deltoid muscle) – atrophy of the skin and subcutaneous tissue.

Other: development or exacerbation of infections (concomitant use of immunosuppressants and vaccination contribute to this side effect), leukocyturia, withdrawal syndrome.

With intravenous administration – arrhythmias, “flushing” of blood to the face, seizures.

With Topical Application rarely – itching, hyperemia, burning, dryness, folliculitis, acneiform eruption, hypopigmentation, perioral dermatitis, allergic dermatitis, skin maceration, secondary infection, skin atrophy, striae, miliaria. With prolonged use or application to large areas of the skin, the development of systemic side effects characteristic of corticosteroids is possible.

Contraindications

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

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, pronounced periarticular osteoporosis, absence of signs of inflammation in the joint (“dry” joint, e.g., in osteoarthritis without synovitis), pronounced bone destruction and joint deformity (sharp narrowing of the joint space, ankylosis), joint instability as an outcome of arthritis, aseptic necrosis of the epiphyses of bones forming the joint.

For Topical Application: rosacea, acne and acne vulgaris (juvenile acne); primary viral skin infections (including chickenpox).

Use in Pregnancy and Lactation

Use during pregnancy is possible only in exceptional cases for strict indications.

If use during lactation is necessary, breastfeeding should be discontinued.

Use in Hepatic Impairment

Use with caution in severe chronic hepatic insufficiency.

Use in Renal Impairment

Use with caution in severe chronic renal insufficiency, nephrourolithiasis.

Pediatric Use

Topical application is contraindicated in children under 1 year of age. Parenteral use is contraindicated in children under 3 years of age.

Betamethasone should be used in children strictly according to indications, in age-appropriate recommended doses and dosage forms, under medical supervision.

Children undergoing parenteral therapy (especially long-term) should be closely monitored for possible growth retardation and development of adrenal cortex insufficiency.

Geriatric Use

Prescribe with caution to elderly patients to avoid worsening of concomitant diseases.

Special Precautions

Use with caution in 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), 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.

Use with caution within 8 weeks before and 2 weeks after vaccination, with lymphadenitis after BCG vaccination, with immunodeficiency states (including AIDS or HIV infection).

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

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

If intra-articular injection is necessary, use with caution in patients with a generally severe condition, ineffectiveness (or short duration) of the action of 2 previous injections (taking into account the individual properties of the corticosteroids used).

When taken orally, it is necessary to monitor blood glucose levels, blood pressure, and indicators of water-electrolyte balance. In case of irritation or symptoms of hypersensitivity to betamethasone, treatment should be discontinued and appropriate therapy carried out. If a secondary infection occurs, treatment with appropriate antimicrobial agents is carried out.

Not indicated for the treatment of hyaline membrane disease of the newborn.

Should not be used topically for the treatment of primary skin lesions in fungal (e.g., candidiasis, trichophytosis) and bacterial (e.g., impetigo) infections, perianal and anogenital itching.

Drug Interactions

With simultaneous use with cardiac glycosides, their effect is enhanced; with diuretics – potassium excretion increases; with hypoglycemic drugs, oral anticoagulants – their effect is weakened; with NSAIDs – the risk of erosive-ulcerative lesions and gastrointestinal bleeding increases.

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.