Bemedozon

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BEMEDOZON (BEMEDOZON)

Composition:

Active substance: betamethasone;

1 ml of solution contains 5.3 mg of betamethasone sodium phosphate calculated as 100 % substance, equivalent to 4.0 mg of betamethasone;

Excipients: disodium edetate, disodium phosphate dihydrate, concentrated phosphoric acid, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group. Corticosteroids for systemic use. Glucocorticoids. Betamethasone. ATC code H02AB01.

Pharmacological Properties.

Pharmacodynamics.

Betamethasone is a synthetic glucocorticoid agent for systemic use. It exerts a pronounced anti-inflammatory, anti-rheumatic, and anti-allergic effect in the treatment of conditions responsive to corticosteroid therapy. It modifies the body's immune responses. Betamethasone has high glucocorticoid activity and weak mineralocorticoid activity.

Pharmacokinetics.

Betamethasone is rapidly absorbed from the injection site. Maximum plasma concentration is reached within 1 hour. Betamethasone is almost completely eliminated within 24 hours. It is metabolized in the liver. The elimination half-life is approximately 300 minutes. In patients with liver disease, betamethasone clearance is slower. Plasma protein binding is high. It has been demonstrated that clinical efficacy depends more on the level of the unbound fraction of corticosteroid than on the total plasma concentration. There is no correlation between plasma corticosteroid levels and the duration of therapeutic effect. Betamethasone readily crosses the placental, blood-brain, and other histohematic barriers and penetrates into breast milk. It is excreted by the kidneys.

Clinical characteristics.

Indications.

For the treatment of various endocrine, rheumatic diseases, collagenoses, dermatological, allergic, ophthalmological, gastrointestinal, respiratory, hematological, and other disorders responsive to corticosteroid therapy. Corticosteroid hormonal therapy is adjunctive to conventional therapy and is not a substitute. This medication is indicated when a rapid, intensive corticosteroid effect is necessary or desirable. Betamethasone is intended for rapid and potent therapeutic effect.

Endocrine disorders: primary and secondary adrenal insufficiency (in combination with mineralocorticoids, if possible); acute adrenal insufficiency; preoperative supportive therapy (as well as in cases of trauma and concomitant illnesses) in known or suspected adrenal insufficiency; shock unresponsive to conventional therapy when adrenal cortical insufficiency is suspected; bilateral adrenalectomy; congenital adrenal hyperplasia; acute thyroiditis, non-infectious thyroiditis, and thyroid storm; hypercalcemia associated with malignancy.

Cerebral edema (elevated intracranial pressure): the clinical benefit of adjunctive corticosteroid therapy in cerebral edema is likely achieved through suppression of cerebral inflammation. Corticosteroids should not be considered a substitute for neurosurgical intervention. They assist in reducing or preventing cerebral edema associated with surgical and other brain injuries, cerebrovascular events, and primary or metastatic brain tumors.

Cases of renal allograft rejection: the efficacy of the drug has been demonstrated in the treatment of acute primary rejection and classic delayed rejection, in combination with conventional therapy, for the prevention of renal transplant rejection.

Antenatal use for prevention of respiratory distress syndrome in premature newborns: the drug is indicated for prophylactic treatment of hyaline membrane disease in premature infants when administered to mothers (up to 32 weeks of gestation) prior to delivery.

Musculoskeletal disorders: as adjunctive therapy for short-term use (to manage acute episodes or exacerbations) in rheumatoid arthritis; osteoarthritis (post-traumatic or with synovitis); psoriatic arthritis; ankylosing spondylitis; acute gouty arthritis; acute and subacute bursitis; acute rheumatic fever; fibrositis; epicondylitis; acute nonspecific tenosynovitis; myositis; calluses. Treatment of cystic tumors of aponeurosis or tendons (ganglia).

Collagenoses: during exacerbations or as supportive therapy in selected cases of systemic lupus erythematosus, acute rheumatic carditis, scleroderma, and dermatomyositis.

Dermatological disorders: pemphigus; herpes gestationis; severe erythema multiforme (Stevens-Johnson syndrome); exfoliative dermatitis; mycosis fungoides; severe psoriasis, allergic eczema (chronic dermatitis), severe seborrheic dermatitis. Local application is indicated for keloids; limited areas of hypertrophy, infiltration, and inflammation in lichen planus, psoriatic plaques, granuloma annulare, and chronic simple lichen (neurodermatitis); discoid lupus erythematosus; diabetic lipoid necrobiosis; focal alopecia.

Allergic disorders: management of severe allergic conditions not adequately controlled by conventional therapy, such as seasonal or perennial allergic rhinitis, nasal polyps, bronchial asthma (including status asthmaticus), contact dermatitis, atopic dermatitis (neurodermatitis), allergic reactions to drugs and blood transfusions; acute non-infectious laryngeal edema.

Ophthalmological disorders: severe, acute, and chronic allergic and inflammatory conditions of the eye and adjacent tissues, such as allergic conjunctivitis, keratitis, allergic marginal corneal ulcers, herpes zoster ophthalmicus, iritis and iridocyclitis, chorioretinitis, anterior segment inflammation, diffuse posterior uveitis and choroiditis, optic neuritis; sympathetic ophthalmia.

Respiratory disorders: symptomatic sarcoidosis; unresolved Löffler's syndrome; berylliosis; fulminant and disseminated pulmonary tuberculosis (in conjunction with specific antituberculosis therapy); aspiration pneumonia.

Hematological disorders: idiopathic or secondary thrombocytopenia in adults; acquired (autoimmune) hemolytic anemia; erythroblastopenia (RBC anemia); congenital (erythroid) hypoplastic anemia; transfusion reactions.

Gastrointestinal disorders: nonspecific ulcerative colitis; regional enteritis.

Oncological disorders: palliative treatment of leukemia and lymphomas in adults; acute leukemia in children.

Edema: to enhance induction of diuresis or remission of proteinuria in idiopathic nephrotic syndrome or nephrotic syndrome due to systemic lupus erythematosus, in the absence of uremia.

Other: tuberculous meningitis with subarachnoid block or risk thereof, in conjunction with specific antituberculosis chemotherapy; trichinellosis with neurological and myocardial involvement.

Contraindications.

Systemic fungal infections. Hypersensitivity to betamethasone, to other components of the drug, or to other glucocorticosteroids.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of phenobarbital, rifampicin, phenytoin, or ephedrine may accelerate the metabolism of corticosteroids, resulting in reduced therapeutic effect.

Excessive effects from corticosteroids may occur in patients receiving corticosteroids and estrogens.

Concomitant use of corticosteroids and potassium-depleting diuretics may lead to hypokalemia.

Combined use of corticosteroids with cardiac glycosides may increase the risk of arrhythmias or enhance glycoside toxicity associated with hypokalemia.

Corticosteroids may potentiate potassium loss induced by amphotericin B. In all patients receiving any of these combinations, serum electrolyte concentrations, especially potassium levels, must be closely monitored.

Concomitant use of corticosteroids with indirect-acting anticoagulants may result in enhanced or diminished anticoagulant effects, possibly requiring dose adjustment.

The combined effect of nonsteroidal anti-inflammatory drugs or alcohol with glucocorticosteroids may increase the frequency or severity of gastrointestinal ulceration.

Administration of corticosteroids may reduce blood salicylate concentrations. Acetylsalicylic acid should be used cautiously in combination with corticosteroids in patients with hypoprothrombinemia.

In patients with diabetes mellitus receiving corticosteroids, dosage adjustments of antidiabetic agents may be required.

Glucocorticosteroid treatment may reduce response to somatotropin. During somatotropin therapy, betamethasone doses exceeding 300–450 mcg (0.3–0.45 mg) per square meter of body surface area per day should not be used.

Corticosteroids may affect the results of the nitroblue tetrazolium test for bacterial infection and may lead to false-negative results.

Special precautions for use.

Corticosteroids should be used with caution in patients who have recently suffered myocardial infarction due to the risk of myocardial rupture.

Due to insufficient data on the use of corticosteroids in head trauma or stroke, they should not be used in these conditions.

Cases of pheochromocytoma crisis, including fatal outcomes, have been reported. Corticosteroids should be administered to patients with diagnosed or suspected pheochromocytoma only after appropriate benefit-risk assessment.

Serious neurological complications (some fatal) have been reported following epidural injection of corticosteroids. Cases of spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke have also been reported. These serious neurological complications have occurred regardless of fluoroscopic guidance. Since the safety and efficacy of epidural administration have not been established, corticosteroids are not recommended for epidural use.

Injections should be administered deeply into large muscle masses only to avoid local tissue atrophy.

When injected into soft tissues, affected sites, or intra-articularly, both local and systemic corticosteroid effects may occur.

Joint fluid should be examined to exclude septic processes. Local injections should be avoided in previously infected joints. Marked increase in pain, local swelling, further limitation of joint movement, fever, and malaise are signs of septic arthritis. If sepsis is confirmed, appropriate antimicrobial therapy should be initiated.

Corticosteroids should not be injected into unstable joints, areas of inflammation, or intervertebral spaces. Repeated intra-articular injections in osteoarthritis may increase joint destruction. Direct injection of corticosteroids into tendons should be avoided, as this may lead to delayed tendon rupture.

After intra-articular therapy with betamethasone, the patient should avoid excessive loading of the joint in which symptoms have been alleviated.

Since isolated cases of anaphylactic reactions have occurred in patients receiving parenteral betamethasone therapy, safety precautions should be taken before administration, especially in patients with a history of allergy to any drug.

When switching from parenteral to oral corticosteroid therapy after prolonged treatment, all potential benefits and risks should be considered.

Dosage adjustments may be necessary depending on the course of the disease, including remission or exacerbation, patient response to therapy, and negative changes in emotional or physical status, such as severe infection, surgery, or trauma. After completion of prolonged or intensive glucocorticoid therapy, patients should be monitored closely for up to one year.

Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of infections requiring antifungal treatment.

Corticosteroids may mask signs of infection or lead to new infections. Corticosteroid use reduces host resistance and the ability to localize infection.

With prolonged use, posterior subcapsular cataracts (especially in children), glaucoma with potential optic nerve damage, and increased risk of secondary fungal or viral eye infections may occur. Regular ophthalmological examinations are recommended, especially for patients on long-term therapy (more than 6 weeks).

Use of moderate to high doses of corticosteroids may cause elevated blood pressure, salt and fluid retention, and increased potassium excretion. These effects are less likely with synthetic derivatives (but not at high doses). However, a low-sodium diet and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.

Patients undergoing corticosteroid therapy should not be vaccinated against varicella. Patients receiving corticosteroids, especially at high doses, should not be vaccinated against other infections due to the risk of neurological complications and reduced immune response. However, immunization may be possible in patients receiving corticosteroids as replacement therapy, e.g., in Addison’s disease.

Patients receiving immunosuppressive doses of corticosteroids should avoid contact with individuals with varicella or measles. This is particularly important for children.

In active tuberculosis, corticosteroid therapy should be limited to fulminant or disseminated forms, and corticosteroids should be used only in conjunction with antituberculosis therapy. Patients with latent tuberculosis or a positive tuberculin reaction receiving corticosteroids should be under medical supervision due to the risk of disease reactivation. During prolonged corticosteroid therapy, patients should receive chemoprophylaxis. If chemotherapy includes rifampicin, its effect in enhancing hepatic metabolic clearance of corticosteroids should be considered; corticosteroid dose adjustment may be necessary.

To control treatment, the lowest effective corticosteroid dose should be used, and the dose should be tapered gradually whenever possible.

Rapid withdrawal of corticosteroids may lead to secondary adrenal insufficiency due to drug-induced suppression, which can be minimized by gradual dose reduction. This relative insufficiency may persist for several months after discontinuation of therapy. If a stressful situation occurs during this period, corticosteroid therapy should be reinstated. If the patient is already receiving corticosteroids, the dose may need to be increased. Due to possible impaired mineralocorticoid secretion, salt and/or mineralocorticoids should be administered concomitantly. Dose reduction should be performed under strict medical supervision, and monitoring may be required for up to one year after prolonged therapy or high-dose treatment.

Betamethasone may be used in diabetic patients only for a short period and under strict medical supervision due to its glucocorticoid properties (protein conversion to glucose).

Drug effects are enhanced in patients with hypothyroidism and hepatic cirrhosis.

The drug should be used with caution in cases of ocular herpes zoster due to the risk of corneal perforation.

Psychiatric disorders may occur during corticosteroid therapy (especially in patients with emotional instability or predisposition to psychosis).

The drug should be used with caution in ulcerative colitis with risk of perforation, abscess or other suppurative infections, diverticulitis, intestinal anastomosis, peptic ulcer of the stomach or duodenum, renal insufficiency, arterial hypertension, osteoporosis, myasthenia gravis, glaucoma, acute psychosis, viral and bacterial infections, growth retardation, tuberculosis, Cushing's syndrome, diabetes, heart failure, difficult-to-treat epilepsy, predisposition to thromboembolism or thrombophlebitis, and during pregnancy.

Complications of glucocorticoid therapy depend on dose and duration of treatment; therefore, the benefit-risk ratio should be evaluated for each patient.

In some patients, corticosteroids may cause decreased sperm count and motility.

The total sodium content in 1 ml of solution is 0.06 mmol; thus, the drug is practically sodium-free.

Strict adherence to aseptic techniques is mandatory when using the drug.

Use during pregnancy or breastfeeding.

The safety of using the drug during pregnancy has not been established; therefore, betamethasone should be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.

The appropriateness of antenatal prophylaxis for respiratory distress syndrome after 32 weeks of gestation has not been definitively established. Therefore, physicians should evaluate the benefit-risk ratio for mother and fetus when using corticosteroids after 32 weeks of pregnancy.

Studies have shown an increased risk of neonatal hypoglycemia after short antenatal courses of betamethasone in women at risk of late preterm delivery.

Corticosteroids are not indicated for the treatment of hyaline membrane disease after birth.

For prophylaxis of hyaline membrane disease in preterm infants, corticosteroids should not be administered to women with placental disorders or with pre-eclampsia or eclampsia.

Newborns whose mothers received significant doses of corticosteroids during pregnancy should be examined for signs of adrenal insufficiency. When women received betamethasone injections during pregnancy, infants showed transient suppression of embryonic somatotropin and, apparently, pituitary hormones regulating corticosteroid production in definitive and fetal zones of the adrenal glands. However, suppression of embryonic hydrocortisone did not affect the pituitary-adrenocortical response to stress after birth.

Since corticosteroids cross the placental barrier, newborns and infants born to mothers who received corticosteroids during pregnancy should be carefully monitored, as congenital cataracts (very rare) may occur.

Women who received corticosteroids during pregnancy should be under special observation during and after delivery due to the possible development of adrenal insufficiency (due to delivery-related stress).

Corticosteroids cross the placental barrier and are present in breast milk.

A decision should be made whether to discontinue breastfeeding or to discontinue/abstain from the drug during breastfeeding due to the risk of adverse reactions in infants.

Ability to influence reaction speed when driving or operating machinery.

Betamethasone does not affect the patient's reaction speed when driving or operating machinery. However, in isolated cases, muscle weakness, cramps, dizziness, headache, psychoemotional instability, severe depression up to overt psychotic reactions, and irritability may occur; therefore, it is recommended to refrain from driving or operating machinery during treatment with the drug.

Method of Administration and Dosage

Betamethasone may be administered intravenously, intramuscularly, intra-articularly, locally into the affected sites, as well as into soft tissues.

Dosage and dosing regimen should be individually determined depending on the nature of the disease, its severity, and the effectiveness of the ongoing treatment.

The initial dose for adults is up to 8 mg of betamethasone per day. In milder cases, lower doses may be used. If necessary, initial single doses may be increased. The initial dose should be adjusted until a satisfactory clinical response is achieved. If a clinical response is not obtained after a certain period, betamethasone should be discontinued and the therapy reassessed.

In children, the usual initial intramuscular dose of betamethasone is 20–125 mcg/kg body weight per day. Dosing in younger and older children should be established according to the same principles as in adults (with preference given to strict adherence to doses specified according to age and body weight).

Although betamethasone can be administered via several routes, intravenous administration is recommended in emergency situations.

For intravenous infusion, betamethasone should be administered with 0.9% sodium chloride solution or glucose. Betamethasone should be added to the infusion solution during administration. Unused solution should be stored in a refrigerator and used within 24 hours.

After achieving a positive clinical effect, the initial dose should be gradually reduced at regular intervals to the lowest dose that maintains the required clinical response.

The occurrence of stressful situations in a patient (unrelated to their underlying disease) may necessitate an increase in the dose of betamethasone.

When discontinuing the drug after prolonged use, the dose should be tapered gradually.

Shock. As an adjunctive therapy, betamethasone at a dose of 3 mg per kg of body weight may be administered as a single IV bolus. This dose may be repeated every 4–6 hours if the shock state persists. Administration of high-dose corticosteroids should be discontinued as soon as the patient's condition stabilizes.

Cerebral edema. Improvement in the patient's condition occurs within several hours after administration of 2–4 mg of betamethasone. In comatose patients, the average single dose is 2–4 mg given four times daily.

Rejection reactions of renal allografts. At the first signs and diagnosis of acute or delayed rejection, betamethasone should be administered by intravenous infusion. The initial dose of betamethasone is 60 mg within the first 24 hours. Minor individual dose adjustments are possible.

Antenatal prophylaxis of respiratory distress syndrome in premature newborns. When inducing labor before 32 weeks of gestation or in cases of imminent preterm delivery before 32 weeks due to obstetric complications, it is recommended to administer betamethasone intramuscularly at 4–6 mg every 12 hours (2–4 doses) during the 24–48 hours preceding the expected delivery. Treatment should be initiated at least 24 hours (preferably 48–72 hours) before delivery to allow sufficient time for the corticosteroid effect and reliable clinical outcome.

Betamethasone may also be used prophylactically if the lecithin/sphingomyelin ratio in amniotic fluid is decreased or if the amniotic fluid foam test stability is reduced. When determining the dose in such cases, the above-mentioned recommendations should be followed, including those regarding the timing of administration relative to delivery.

Musculoskeletal disorders, soft tissue diseases

For the prevention of transfusion complications, administer 1 or 2 ml of the drug (4–8 mg of betamethasone) intravenously (immediately before blood transfusion); under no circumstances should betamethasone be added directly to the blood being transfused. In repeated blood transfusions, the total dose of the drug may reach up to 4 doses, which should be administered within 24 hours, if necessary.

Subconjunctivally, usually 0.5 ml of the drug (2 mg of betamethasone) is administered.

Children.

During prolonged treatment of infants and children, growth and development must be closely monitored (due to the potential for growth suppression and suppression of endogenous corticosteroid production).

Children receiving immunosuppressive doses of corticosteroids should avoid contact with individuals infected with varicella (chickenpox) and measles.

Overdose.

Acute overdose of corticosteroids, including betamethasone, is not expected to result in life-threatening conditions. Except in cases of extremely high doses, excessive use of corticosteroids does not typically lead to adverse effects in the absence of specific contraindications, provided there are no conditions such as diabetes, glaucoma, active peptic ulcer, and provided the patient is not taking digitalis preparations, coumarin anticoagulants, or potassium-depleting diuretics.

Treatment. Symptomatic therapy for complications arising from the metabolic effects of corticosteroids, underlying or concomitant diseases, or drug interactions.

Ensure adequate fluid intake and monitor serum and urinary electrolyte levels, paying particular attention to sodium and potassium balance. Electrolyte balance should be corrected as necessary.

Adverse Reactions

The frequency and severity of adverse reactions (as with all glucocorticoids) depend on the dose and duration of therapy. These effects are usually reversible or can be minimized by dose reduction, which is an advantage over abrupt discontinuation of the drug.

Cardiovascular system: congestive heart failure in predisposed patients; arterial hypertension.

Nervous system: dizziness, headache, convulsions, increased intracranial pressure with optic disc swelling (pseudotumor cerebri), usually after completion of treatment, migraine.

Psychiatric disorders: euphoria, emotional instability, mood changes, severe depression up to frank psychotic reactions, particularly in patients with psychiatric history, personality changes, increased irritability, insomnia.

Eye disorders: posterior subcapsular cataract, increased intraocular pressure, glaucoma, exophthalmos.

Endocrine system: secondary adrenocortical and pituitary insufficiency (especially during stress – trauma, surgery, illness), decreased carbohydrate tolerance, manifestation of latent diabetes, increased insulin and oral hypoglycemic agent requirements in diabetic patients, menstrual irregularities, development of Cushingoid state with hirsutism, striae, and acne, suppression of fetal or childhood growth.

Metabolism and nutrition: negative nitrogen balance (due to protein catabolism), lipomatosis including mediastinal and epidural lipomatosis which may cause neurological complications, weight gain. Fluid and electrolyte imbalance may also occur, manifesting as sodium retention, potassium loss, hypokalemic alkalosis, increased calcium excretion, fluid retention, congestive heart failure in sensitive patients, arterial hypertension.

Musculoskeletal and connective tissue disorders: muscle weakness, corticosteroid myopathy, decreased muscle mass, worsening of myasthenia symptoms in severe pseudoparalytic myasthenia, osteoporosis sometimes with severe bone pain and spontaneous fractures (vertebral compression fractures), aseptic necrosis of femoral and humeral heads, pathological fractures of long bones, tendon ruptures, tendon herniation, joint instability (due to repeated intra-articular injections).

Gastrointestinal disorders: hiccup, gastric erosions and ulcers with possible subsequent perforation and hemorrhage, esophageal ulceration, pancreatitis, abdominal distension, ulcerative esophagitis, intestinal perforation, nausea, vomiting.

Skin and subcutaneous tissue disorders: delayed wound healing, thin fragile skin, petechiae and ecchymoses, bruising, atrophy, facial erythema, increased sweating, allergic dermatitis, urticaria, angioneurotic edema.

Immune system disorders: corticosteroids may affect skin test results, mask signs of infection, activate latent infections, and reduce resistance to infections, including to mycobacteria, Candida albicans, and viruses. Anaphylactoid reactions or hypersensitivity reactions, and hypotensive or shock-like reactions may also occur.

Additionally, adverse reactions associated with parenteral corticosteroid therapy include rare cases of blindness related to therapy at the site of involvement – in the face and head area, pigmentary changes, cutaneous and subcutaneous atrophy, sterile abscesses, post-injection inflammation (after intra-articular administration), and Charcot-type arthropathy.

Secondary suppression of the pituitary and adrenal cortex function under stress conditions (trauma, surgery, or illness).

Repeated intra-articular injections may lead to joint damage. There is a risk of infection.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients or their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Information System of Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Do not freeze. Keep out of reach of children.

Packaging. 1 ml in an ampoule, 100 ampoules per pack or 5 ampoules in a blister, 1 or 2 blisters per pack.

Prescription status. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and location of business activity.

36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.