FLOSTERON

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

Composition:

Active ingredient: 1 ml of suspension (1 ampoule) contains 2 mg of betamethasone in the form of betamethasone disodium phosphate and 5 mg of betamethasone in the form of betamethasone dipropionate;

Excipients: disodium hydrogen phosphate dihydrate, sodium chloride, edetate disodium, polysorbate 80, benzyl alcohol, methylparaben (E 218), propylparaben (E 216), sodium carmellose, polyethylene glycols, concentrated hydrochloric acid, water for injections.

Medicinal form. Injection suspension.

Main physicochemical properties: clear, colorless, slightly viscous liquid containing white particles that readily suspend and in which no foreign particles are present.

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

Pharmacological properties.

Pharmacodynamics.

Betamethasone is a synthetic corticosteroid with anti-inflammatory and immunosuppressive effects. In addition, it affects energy metabolism, glucose homeostasis, and (via negative feedback) the secretion of hypothalamic corticotropin-releasing factor and adrenocorticotropic hormone from the anterior pituitary.

Corticosteroids with a 1,2 double bond in the A ring and other substituents at the C16 position of the D ring, such as 9-alpha-fluoro derivatives, exhibit strong corticosteroid activity. These C16 substituents essentially reduce mineralocorticoid activity.

The mechanism of action of corticosteroids is not yet fully understood. There is sufficient evidence indicating that their primary mechanism occurs at the cellular level. Two distinct receptor systems exist within the cellular cytoplasm. Glucocorticoid receptors mediate the anti-inflammatory and immunosuppressive effects of corticosteroids, as well as regulation of glucose homeostasis, whereas mineralocorticoid receptors regulate sodium and potassium metabolism and water-electrolyte balance.

Corticosteroids are lipophilic and readily penetrate the cell membrane into the target cell. Hormone binding to its receptor induces a conformational change in the receptor, increasing its affinity for DNA. The hormone-receptor complex enters the cell nucleus and binds to a regulatory region of the DNA molecule known as the "glucocorticoid response element" (GRE). The activated receptor, bound to GRE or specific genes, regulates mRNA transcription—either increasing or decreasing it. The newly formed mRNA is transported to ribosomes, resulting in the synthesis of new proteins. Depending on the target cells and cellular processes, the production of certain proteins may be enhanced (e.g., tyrosine transaminase in liver cells) or suppressed (e.g., IL-2 in lymphocytes). Since glucocorticoid receptors are present in all tissues, it is believed that corticosteroids act in most cells of the body.

The anti-inflammatory and immunosuppressive effects of corticosteroids are based on molecular and biochemical actions. The molecular anti-inflammatory effect arises from the binding of corticosteroids to glucocorticoid receptors and the subsequent alteration in the expression of several genes that regulate the production of various signaling molecules, proteins, and enzymes involved in the inflammatory response. The biochemical anti-inflammatory effect of corticosteroids results from the inhibition of the formation and function of humoral inflammatory mediators: prostaglandins, thromboxanes, cytokines, and leukotrienes. Betamethasone reduces leukotriene synthesis by inhibiting the release of arachidonic acid from cellular phospholipids, achieved through inhibition of phospholipase A2 activity. This inhibition is not direct but occurs via an increase in lipocortin (macrocortin) concentration, which is an inhibitor of phospholipase A2. The inhibitory effect of betamethasone on prostaglandin and thromboxane formation results from its suppressive action on the synthesis of specific mRNA and cyclooxygenase. Additionally, by increasing lipocortin concentration, betamethasone reduces the formation of platelet-activating factors (PAF). Another biochemical anti-inflammatory effect includes the reduction in tumor necrosis factor (TNF) and IL-1 production.

Corticosteroids regulate glucose homeostasis and affect sodium and potassium metabolism, electrolyte balance, and water balance. The anti-inflammatory potency of betamethasone exceeds that of hydrocortisone by 30 times, and it lacks significant mineralocorticoid activity.

Pharmacokinetics.

Betamethasone sodium phosphate is a rapidly soluble component that is quickly absorbed into tissues and provides a rapid onset of action. Prolonged action is provided by betamethasone dipropionate, which is absorbed more slowly.

The combination of these components ensures both rapid and prolonged effects. Depending on the route of administration (intra-articular, periarticular, local lesion site, intradermal, and in some cases intramuscular), either a systemic or local effect is achieved.

After intra-articular administration, the maximum plasma concentration of the betamethasone combination is reached within 30 minutes.

Following absorption, topical corticosteroids are metabolized via pharmacokinetic pathways similar to those of systemically administered corticosteroids. Corticosteroids bind to plasma proteins to varying degrees. They are primarily metabolized in the liver and excreted in urine. Some topical corticosteroids and their metabolites are excreted via bile.

Metabolites are broken down in the liver and are primarily eliminated by the kidneys, with only a minor fraction excreted in bile.

Clinical characteristics.

Indications.

Dermatological diseases.

Atopic dermatitis (nummular eczema), neurodermatitis, contact dermatitis, severe solar dermatitis, urticaria, lichen planus, insulin-induced lipodystrophy, alopecia areata, discoid lupus erythematosus, psoriasis, keloid scars, pemphigus vulgaris, herpetic dermatitis, cystic acne.

Rheumatic diseases.

Rheumatoid arthritis, osteoarthritis, bursitis, tenosynovitis, tendinitis, peritendinitis, ankylosing spondylitis, epicondylitis, radiculitis, coccygodynia, sciatica, lumbago, torticollis, ganglion cyst, exostosis, fasciitis, acute gouty arthritis, synovial cysts, Morton's disease, cuboiditis, foot disorders, bursitis associated with hard corns, heel spurs, hallux rigidus.

Allergic conditions.

Bronchial asthma, status asthmaticus, hay fever, severe allergic bronchitis, seasonal and perennial allergic rhinitis, angioneurotic edema, contact dermatitis, atopic dermatitis, serum sickness, hypersensitivity reactions to drugs or insect bites.

Collagen diseases.

Systemic lupus erythematosus, scleroderma, dermatomyositis, polyarteritis nodosa.

Oncological diseases.

Palliative therapy of leukemia and lymphoma in adults, acute leukemia in children.

Other diseases.

Adrenogenital syndrome, ulcerative colitis, Crohn's disease, sprue, hematological disorders requiring corticosteroid therapy, nephritis, nephrotic syndrome.

Primary and secondary adrenal insufficiency (with mandatory concomitant administration of mineralocorticoids).

Contraindications.

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

Intramuscular administration is contraindicated in patients with idiopathic thrombocytopenic purpura.

Infections at the site of application. Severe myopathies (except myasthenia gravis). Lymphadenitis following BCG vaccination.

Interaction with other medicinal products and other forms of interaction.

Barbiturates, hydantoins, rifampicin, ephedrine: concomitant use of phenobarbital, rifampicin, phenytoin, or ephedrine may enhance the metabolism of the drug, thereby reducing its therapeutic activity.

Diuretics: combination with diuretics such as thiazides may increase the risk of glucose intolerance. Concurrent use of Flosteron with potassium-wasting diuretics increases the likelihood of developing hypokalemia.

Oral contraceptives: concomitant use of oral contraceptives may prolong the elimination half-life of corticosteroids, thereby increasing their biological effect and the frequency of adverse effects.

Cardiac glycosides: potassium deficiency enhances the effect of glycosides. Concomitant use of glucocorticosteroids and cardiac glycosides increases the risk of arrhythmias or digitalis toxicity (due to hypokalemia).

Saluretics, amphotericin B: additional potassium loss. Flosteron may potentiate potassium loss induced by amphotericin B. In all patients receiving any of these drug combinations, careful monitoring of serum electrolytes, particularly serum potassium, is required.

Coumarin derivatives: anticoagulant effect is reduced. Concurrent use of Flosteron and indirect anticoagulants may alter blood coagulation speed, necessitating dose adjustments.

Nonsteroidal anti-inflammatory drugs (NSAIDs): combined use of glucocorticosteroids with NSAIDs, ethanol, or ethanol-containing preparations increases the risk of gastrointestinal bleeding and ulcer formation or worsening of their severity.

Salicylates: aspirin is known to be harmful to the stomach, and glucocorticosteroids may mask these adverse effects. The mechanism is unknown. When used concomitantly, glucocorticosteroids may reduce plasma salicylate concentrations. When tapering or discontinuing corticosteroid therapy, patients should be monitored for possible salicylate poisoning. Combination of corticosteroids with salicylates may increase the frequency and severity of gastrointestinal ulcers. There is an increased risk of gastrointestinal bleeding and ulcers, as well as a risk of reduced aspirin efficacy.

Oral antidiabetic agents: reduced blood glucose levels. In diabetic patients, dosage adjustments of oral antidiabetic agents or insulin may occasionally be necessary, considering the tendency of corticosteroids to cause hyperglycemia.

Growth hormones: the effect of growth hormones may be weakened or inhibited. Concomitant administration of glucocorticosteroids and somatotropin may lead to slowed absorption of the latter. Doses of betamethasone exceeding 300–450 µg (0.3–0.45 mg) per 1 m² body surface area per day should be avoided during somatotropin therapy.

Chloroquine, hydroxychloroquine, mefloquine: increased risk of myopathies and cardiomyopathies.

Isoniazid: glucocorticosteroids increase the clearance of isoniazid and reduce its serum concentration.

Bupropion: concomitant use with systemic glucocorticosteroids increases the risk of seizures.

Antibiotics: macrolide antibiotics have been reported to significantly reduce corticosteroid clearance.

Local anesthetics: when betamethasone is used locally, compatibility with added (local) anesthetics should always be verified.

CYP3A inhibitors (including products containing cobicistat): combined therapy with CYP3A inhibitors, including those containing cobicistat, is expected to increase the risk of systemic adverse effects. Concomitant use should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side effects; if such use is necessary, patients should be monitored for the development of systemic corticosteroid adverse effects.

Live bacterial or viral vaccines: if corticosteroid treatment is administered within 8 weeks before or 2 weeks after active immunization, reduced or absent immunization response should be expected.

Inactivated and toxoid vaccines: inadequate protection from vaccination may occur. Immune response to vaccination with inactivated or toxoid vaccines may be absent or reduced during concomitant systemic glucocorticosteroid therapy. Systemic use of glucocorticosteroids at pharmacological doses may suppress immune responses upon exposure to pathogens, potentially interfering with sufficient antibody (immunoglobulin) production. The primary immune response is mainly affected, but the secondary immune response may also be impaired.

Effect on laboratory test results.

Corticosteroids may interfere with the nitroblue tetrazolium reduction test and produce false-negative results.

When a patient is undergoing corticosteroid therapy, this must also be taken into account when interpreting biological parameters and analyses (skin tests, thyroid hormone levels).

Special precautions for use.

Fluosteron suspension is not intended for intravenous or subcutaneous administration.

In each case, the risks must be weighed against the expected therapeutic benefit, and the underlying disease must be monitored.

Strict adherence to aseptic techniques is mandatory when using this medicinal product.

The physician prescribing Fluosteron must consider the possibility of systemic effects of the drug.

Any administration of the drug (into soft tissues, lesion site, intra-articular) may result in systemic effects as well as pronounced local effects.

Adverse effects and contraindications of systemic glucocorticoid therapy should also be considered even with local application, especially with high doses, repeated use, and application to large joints.

The Fluosteron formulation contains two esters of betamethasone, one of which—betamethasone sodium phosphate—is rapidly absorbed from the injection site. Therefore, it should be considered that this soluble component of the drug may exert systemic effects.

Symptoms of adrenal insufficiency include malaise, muscle weakness, psychiatric disorders, drowsiness, muscle and bone pain, skin desquamation, dyspnea, anorexia, nausea, vomiting, fever, hypoglycemia, hypotension, dehydration, and even fatal outcomes following abrupt discontinuation of treatment. Treatment of adrenal insufficiency consists of administering corticosteroids, mineralocorticoids, water, sodium chloride, and glucose.

Abrupt withdrawal or dose reduction after prolonged use (especially with very high doses or after a short treatment period) or during periods of increased corticosteroid requirements (due to stress: infection, trauma, surgery) may exacerbate adrenal insufficiency. In such cases, dosage should be tapered gradually. In times of stress, corticosteroid therapy may need to be reinstituted or the dose increased. Dose reduction must be performed under strict medical supervision, and monitoring of the patient may be required for up to 1 year after discontinuation of prolonged or high-dose therapy.

Rare cases of anaphylactoid/anaphylactic reactions with possible shock have been observed in patients receiving parenteral corticosteroids; therefore, appropriate precautionary measures should be taken before drug administration, particularly if the patient has a history of allergy to any component of the drug.

During prolonged corticosteroid therapy, transition from parenteral to oral administration should be considered after evaluating potential benefits and risks.

Intramuscular injections of glucocorticosteroids must be administered deeply into the muscle to prevent local tissue atrophy.

Intra-articular injections must be performed only by medical personnel. Analysis of synovial fluid is required to exclude septic processes. Marked increase in pain, local swelling, elevated temperature of surrounding tissues, discomfort, and further limitation of joint mobility may indicate septic arthritis. If diagnosis is confirmed, antibacterial therapy must be initiated. Glucocorticosteroids should not be administered into unstable joints, infected areas, previously infected joints, or the intervertebral space. Repeated intra-articular injections in osteoarthritis may increase the risk of joint destruction. Corticosteroid injections directly into tendons should be avoided, as this may subsequently lead to tendon rupture. Intra-articular injections are contraindicated in periarticular calcinosis and Charcot joint.

Prolonged and repeated use of glucocorticoids in heavily loaded joints may exacerbate wear-related changes. It is important to clearly instruct the patient not to overuse joints after symptomatic improvement, while inflammatory processes are still ongoing.

Special patient groups at risk

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

Enhanced effects of glucocorticosteroids have been observed in patients with hypothyroidism or liver cirrhosis. Administration of Fluosteron should be avoided in patients with herpetic eye infections (due to the risk of corneal perforation).

Psychiatric disturbances (especially in patients with emotional instability or predisposition to psychosis) may occur during treatment with this drug.

Precautions are necessary in the following conditions: nonspecific ulcerative colitis, risk of perforation, abscess or other pyogenic infections; diverticulitis; intestinal anastomoses; peptic ulcer of the stomach and duodenum; renal insufficiency; arterial hypertension; osteoporosis; severe myasthenia; glaucoma; acute psychosis; viral and bacterial infections; growth retardation; tuberculosis; Cushing's syndrome; diabetes; heart failure; complicated epilepsy; predisposition to thromboembolism or thrombophlebitis; and during pregnancy.

Prior to initiating corticosteroid therapy, a thorough patient examination is required, including exclusion of peptic ulcer disease of the stomach and duodenum. To prevent gastrointestinal ulcers, administration of acid-suppressing agents and careful monitoring are recommended.

During any prolonged corticosteroid therapy, regular monitoring of blood glucose levels and coagulation, as well as spinal X-rays and ophthalmological examinations, is necessary.

During prolonged treatment, in addition to monitoring related to the underlying disease, periodic assessment for possible adverse effects should be performed at appropriate intervals, depending on dosage and the patient's initial condition.

Such monitoring is mandatory during concomitant therapy for the underlying disease: diabetes mellitus, tuberculosis, acute and chronic bacterial and amoebic infections, hypertensive disease, thromboembolic processes, cardiac and renal insufficiency, acute glomerulonephritis, and chronic nephritis.

Corticosteroid therapy should be administered only with all necessary precautions if concomitant treatment is possible to control the underlying disease (antidiabetic agents, antituberculosis drugs, antibiotics, anticoagulants, etc.).

Since complications associated with corticosteroid therapy depend on dose and duration of treatment, the risk-benefit ratio must be considered for each patient when selecting dosage and treatment duration.

Patients receiving a course of glucocorticosteroid therapy should not be vaccinated against smallpox. Other immunizations should not be administered to patients receiving corticosteroids (especially at high doses) due to the risk of neurological complications and poor immune response (lack of antibody formation). Immunization may be possible during replacement therapy (e.g., in Addison's disease).

Patients, particularly children, receiving Fluosteron at immunosuppressive doses should avoid contact with individuals with chickenpox or measles.

Corticosteroids may mask some signs of infectious disease or complicate detection of infection. Due to decreased resistance, new infections may arise during treatment.

Administration of the drug in active tuberculosis is possible only in cases of rapidly progressive or disseminated tuberculosis, in combination with adequate antituberculosis therapy. If corticosteroids are prescribed to patients with latent tuberculosis or those reacting to tuberculin, strict monitoring is required, as reactivation of the disease may occur. Patients undergoing prolonged corticosteroid therapy should also receive chemoprophylaxis. If patients are using rifampicin in a chemoprophylaxis regimen, the enhanced effect of corticosteroids due to increased hepatic metabolic clearance should be monitored; dose adjustment of corticosteroids may be necessary.

Prolonged use of glucocorticosteroids may lead to the development of posterior subcapsular cataracts (especially in children), glaucoma with possible optic nerve damage, and may promote secondary eye infections (fungal or viral). Regular ophthalmological examination is necessary, especially for patients receiving Fluosteron for more than 6 weeks.

Fluosteron is not indicated alone in the presence of local or systemic infections (bacterial, viral, fungal), but may be used with sufficient caution in combination with antimicrobial therapy.

Results from a single, multicenter, randomized, controlled study with another corticosteroid (methylprednisolone hemisuccinate) showed increased early mortality (within 2 weeks) and late mortality (within 6 months) in patients with traumatic brain injury who received methylprednisolone compared to placebo. The causes of death in the methylprednisolone group were not established. This study did not include patients with clear indications for corticosteroid use.

Moderate and high doses of corticosteroids may cause elevated blood pressure, fluid and sodium retention in tissues, and increased potassium excretion (manifesting as edema and cardiac disturbances). These effects are less likely with synthetic derivatives unless used at high doses. A low-salt diet and additional potassium supplementation are recommended. All corticosteroids accelerate calcium excretion from the body.

Acetylsalicylic acid should be used with caution in combination with this drug in patients with hypoprothrombinemia due to the potential for increased bleeding.

One should also remember the possibility of developing secondary adrenal insufficiency for several months after therapy discontinuation.

Administration of glucocorticosteroids may alter sperm motility and count.

Vision disturbances

Vision disturbances may occur with systemic or local use of corticosteroids. If symptoms such as blurred vision or other visual disturbances occur, the patient should undergo an ophthalmological examination to evaluate possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after systemic and local corticosteroid use.

Cases of potentially fatal pheochromocytoma crisis have been reported after administration of systemic corticosteroids. Corticosteroids should be prescribed to patients with suspected or diagnosed pheochromocytoma only after careful risk-benefit assessment.

The excipient benzyl alcohol contained in Fluosteron is contraindicated in infants and children under 3 years of age. This preparation should not be used in premature infants or full-term newborns.

Since corticosteroids may retard growth in children, including infants, and suppress endogenous corticosteroid production, careful monitoring of growth and development is essential during prolonged treatment.

Methylparaben and propylparaben usually cause delayed-type reactions such as contact dermatitis and rarely cause immediate reactions such as urticaria and bronchospasm.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially sodium-free.

Use during pregnancy or breastfeeding.

Due to the lack of controlled safety studies in pregnant women, breastfeeding mothers, and women of reproductive age, Fluosteron should be prescribed only after careful evaluation of the benefit to the mother versus the potential risk to the fetus/child.

Pregnancy

When prescribing corticosteroids during the prenatal period, the benefits and disadvantages of such treatment and the clinical effect must be weighed against adverse effects (including growth suppression and increased risk of infection).

In some cases, a course of corticosteroid therapy may be necessary during pregnancy or even dose escalation (e.g., in corticosteroid replacement therapy).

Intramuscular administration of betamethasone significantly reduces the incidence of fetal respiratory distress when administered more than 24 hours before delivery (up to 32 weeks of gestation).

Published data indicate that the issue of prophylactic use of corticosteroids after 32 weeks of gestation remains controversial. Therefore, when prescribing corticosteroids after 32 weeks of gestation, the physician must carefully weigh all benefits of such treatment against potential risks for the woman and fetus.

Corticosteroids are not prescribed for the treatment of hyaline membrane disease in newborns.

In prophylactic treatment of hyaline membrane disease in preterm infants, corticosteroids should not be administered to pregnant women with pre-eclampsia and eclampsia or those with placental disorders.

Infants born to mothers who received significant doses of corticosteroids during pregnancy should be under medical supervision (for early detection of signs of adrenal insufficiency).

Administration of betamethasone to pregnant women before delivery has been associated with transient suppression of embryonic growth hormone activity and possibly pituitary hormones regulating steroid production in both definitive and fetal zones of the fetal adrenal glands. However, suppression of fetal hydrocortisone production did not affect pituitary-adrenal responses to stress after delivery.

Since corticosteroids cross the placenta, newborns and infants whose mothers received corticosteroids during pregnancy should be carefully examined for rare possible congenital cataracts.

Women who received corticosteroids during pregnancy should be monitored during and after labor, as well as during delivery, to detect adrenal insufficiency due to delivery-related stress.

Studies have shown an increased risk of neonatal hypoglycemia after antenatal administration of a short course of betamethasone to women at risk of late preterm birth.

Breastfeeding

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

If administration of Fluosteron is necessary, a decision should be made regarding discontinuation of breastfeeding or discontinuation of therapy, considering the importance of treatment for the mother (due to possible adverse effects in children).

Ability to affect reaction speed when driving or operating machinery.

Fluosteron generally does not affect the patient's reaction speed when driving or operating machinery. However, in individual cases, muscle weakness, cramps, visual disturbances, dizziness, headache, mood changes, depression (with pronounced psychotic reactions), and increased irritability may occur; therefore, it is recommended to refrain from driving or operating machinery during treatment with this drug.

Method of Administration and Dosage.

Flosteron is recommended for intramuscular administration when systemic delivery of a glucocorticosteroid is required; directly into affected soft tissue or as intra-articular and periarticular injections in arthritis; as intradermal injections in various skin diseases; or as local injections into the lesion site in certain foot disorders.

The dosage regimen and route of administration should be determined individually by a physician depending on the indication, severity of the disease, and the patient's response to treatment.

The dose should be the lowest possible, and the duration of treatment should be as short as possible.

The dose should be adjusted to achieve a satisfactory clinical effect. If a satisfactory clinical response is not observed within a certain period of time, treatment with the drug should be discontinued gradually by tapering the dose, and alternative appropriate therapy should be initiated.

In cases of favorable response, the appropriate maintenance dose should be established by gradually reducing the initial dose at acceptable intervals until the lowest effective dose producing the desired clinical response is reached.

Flosteron suspension is not intended for intravenous or subcutaneous administration.

Systemic Administration.

The initial dose of the drug is generally 1–2 mL. Repeat administration may be necessary depending on the patient's condition. The drug should be administered deep intramuscularly into the gluteal muscle:

• In severe conditions (e.g., systemic lupus erythematosus and status asthmaticus) requiring emergency intervention, the initial dose may be 2 mL;
• For various dermatological conditions, 1 mL of the drug is usually sufficient;
• In respiratory disorders, the effect of the drug begins within several hours after intramuscular injection of Flosteron; in bronchial asthma, hay fever, allergic bronchitis, and allergic rhinitis, significant improvement is typically achieved after administration of 1–2 mL of the drug;
• In acute and chronic bursitis, the intramuscular dose is 1–2 mL of the drug. Repeated administrations may be required if necessary.

Local Administration.

Concomitant use of a local anesthetic agent is necessary only in rare cases (the injection is nearly painless). If simultaneous administration of a local anesthetic is desired, 1% or 2% solutions of procaine hydrochloride or lidocaine, or similar local anesthetics free of parabens, should be used. Anesthetics containing methylparaben, propylparaben, phenol, or other similar substances must not be used. When combining an anesthetic with Flosteron, first draw the required dose of Flosteron from the vial into the syringe, then add the required amount of local anesthetic from the ampoule into the same syringe, and gently shake the syringe briefly.

In acute bursitis (subdeltoid, subscapular, olecranon, and prepatellar), injection of 1–2 mL of Flosteron into the bursa may relieve pain and fully restore mobility within several hours.

Treatment of chronic bursitis should be performed with lower doses after resolution of the acute episode.

In acute tenosynovitis, tendinitis, and peritendinitis, a single injection of Flosteron provides symptomatic relief; in chronic cases, the injection should be repeated depending on the response. Direct injection of the drug into tendons should be avoided.

In rheumatoid arthritis and osteoarthritis, intra-articular injection of 0.5–2 mL of the drug reduces joint pain, tenderness, and stiffness within 2–4 hours after administration. The duration of therapeutic effect varies significantly and may last 4 weeks or longer.

Recommended doses for injection: into large joints – 1–2 mL, into medium joints – 0.5–1 mL, into small joints – 0.25–0.5 mL.

In dermatological conditions, intradermal injection of the drug directly into the lesion site is effective. Inject 0.2 mL/cm² of Flosteron into the skin (not subcutaneously) using a tuberculin syringe and a needle with a diameter of approximately 0.9 mm. The total volume administered at any injection site should not exceed 1 mL.

In foot disorders responsive to corticosteroids, bursitis under a callus may be treated by two consecutive injections of 0.25 mL each. Rapid relief may be achieved in conditions such as hallux rigidus, tailor’s bunion, and acute gouty arthritis.

Recommended single doses of Flosteron (with intervals of 1 week between injections): for hard callus – 0.25–0.5 mL; for heel spur – 0.5 mL; for hallux rigidus – 0.5 mL; for tailor’s bunion – 0.5 mL; for ganglion cyst – 0.25–0.5 mL; for tenosynovitis – 0.5 mL; for cuboid bone inflammation – 0.5 mL; for acute gouty arthritis – 0.5–1 mL. A tuberculin syringe with a needle of approximately 1 mm diameter is recommended for administration.

If a stress situation occurs or is anticipated (unrelated to the underlying disease), dose adjustment with temporary dose increase may be necessary.

Discontinuation of the drug after prolonged therapy should be carried out gradually by tapering the dose. Patients should be monitored for at least one year after long-term therapy or after high-dose treatment.

Children.

There are insufficient clinical data on the use of the drug in children; therefore, its use in this age group is not recommended (due to potential growth retardation and risk of secondary adrenal insufficiency).

Since corticosteroids may impair growth in children, including infants, and may suppress endogenous corticosteroid production, careful monitoring of growth and development is essential during long-term treatment.

Overdose.

Acute overdose of betamethasone does not typically result in life-threatening situations. Administration of high doses of glucocorticosteroids over several days does not usually lead to adverse consequences (except in cases of extremely high doses, or in patients with diabetes mellitus, glaucoma, acute exacerbation of erosive-ulcerative gastrointestinal lesions, or in patients concurrently receiving cardiac glycosides, indirect anticoagulants, or potassium-depleting diuretics).

Treatment. Careful medical monitoring is required. Adequate fluid intake should be maintained, and electrolyte levels in plasma and urine should be monitored (particularly sodium and potassium balance). Appropriate corrective therapy should be initiated if electrolyte imbalances are detected.

Adverse Reactions

Undesirable effects, as with other glucocorticosteroids, are dose- and duration-dependent. These reactions are usually reversible and may be minimized by dose reduction.

Immune system disorders: Increased susceptibility to infections and severity of infections with suppression of clinical signs and symptoms; hypersensitivity reactions (shock-like states, drop in blood pressure); anaphylactic and anaphylactoid reactions.

Endocrine system disorders: Clinical features of Cushing's syndrome; fetal or childhood growth retardation; impaired carbohydrate tolerance; manifestation of latent diabetes mellitus; worsening of pre-existing diabetes mellitus; secondary adrenocortical and pituitary insensitivity, especially under stress conditions such as trauma, surgery, or illness; menstrual irregularities; increased requirement for insulin or oral antidiabetic agents in diabetic patients.

Metabolic disorders: Negative nitrogen balance due to protein catabolism; lipomatosis, including mediastinal and epidural lipomatosis, which may lead to neurological complications; weight gain; sodium and fluid retention; increased potassium excretion; hypokalemic alkalosis; calcium loss.

Psychiatric disorders: Euphoria, mood changes, personality changes, severe depression, irritability, insomnia, psychotic reactions (particularly in patients with psychiatric history), depression.

Nervous system disorders: Seizures; increased intracranial pressure with papilledema (pseudotumor cerebri), usually after discontinuation of therapy; dizziness; headache; migraine.

Eye disorders: Posterior subcapsular cataract; increased intraocular pressure; diplopia (due to pseudotumor cerebri); glaucoma; exophthalmos; blurred vision (see also section "Special precautions").

Cardiac disorders: Congestive heart failure in patients predisposed to this condition.

Vascular disorders: Phlebothrombosis; arterial hypertension.

Gastrointestinal disorders: Hiccups; erosive and ulcerative lesions of the stomach with possible perforation and hemorrhage; esophageal ulceration; pancreatitis; abdominal distension; intestinal perforation; nausea; vomiting.

Skin and subcutaneous tissue disorders: Impaired wound healing; skin atrophy; thinning and weakening of the skin; petechiae and ecchymoses; bruising; purpura; facial erythema; hyperpigmentation; increased sweating; skin reactions such as allergic dermatitis, urticaria, angioneurotic edema; hirsutism; striae; steroid acne; suppression of skin test reactivity.

Musculoskeletal and connective tissue disorders: Muscle weakness; corticosteroid myopathy; loss of muscle mass; worsening of myasthenic symptoms in severe myasthenia gravis; osteoporosis, sometimes with severe bone pain and spontaneous fractures (e.g., vertebral compression fractures); aseptic necrosis of femoral or humeral heads; pathological fractures of long bones; tendon ruptures; joint instability (after repeated intra-articular injections).

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

General disorders and administration site conditions: General disorders and administration site reactions include rare cases of blindness following local application around the mouth and head; hyper- or hypopigmentation; subcutaneous or cutaneous tissue atrophy; sterile abscesses; post-injection flare (following intra-articular injection); Charcot arthropathy.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after drug authorization is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions. Store at temperatures not exceeding 25 °C in the original packaging to protect from light. Keep out of reach of children.

Incompatibilities.

Flosteron suspension may be mixed with local anesthetics in the same syringe; however, compatibility should always be verified.

Packaging. 1 ml of injectable suspension in a vial; 5 vials in a blister pack; 1 blister pack in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

KRKA, d.d., Novo mesto / KRKA, d.d., Novo mesto.

Manufacturer's address and location of operations.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia.