Betaspan^® Depo (Suspension) Instructions for Use

Marketing Authorization Holder

Farmak, JSC (Ukraine)

ATC Code

H02AB01 (Betamethasone)

Active Substances

Betamethasone sodium phosphate (BAN)

Betamethasone (Rec.INN)

Dosage Form

Betaspan® Depo

Injection suspension 5 mg+2 mg/1 ml: amp. 5 pcs.

Dosage Form, Packaging, and Composition

Injection suspension clear, colorless or yellowish, slightly viscous, containing easily suspendable particles of white or almost white color; upon shaking, a white or almost white suspension is formed.

Excipients : methylparahydroxybenzoate (E218) – 1.3 mg, propylparahydroxybenzoate (E216) – 0.2 mg, benzyl alcohol – 9 mg, sodium chloride – 5.5 mg, sodium hydrogen phosphate – 0.6 mg, disodium edetate dihydrate – 0.1 mg, carmellose sodium – 5.2 mg, polysorbate 80 – 0.5 mg, macrogol 4000 – 25 mg, water for injections – up to 1 ml.

1 ml – glass ampoules (1) – blisters made of polymer film (1) – cardboard packs.
1 ml – glass ampoules (5) – blisters made of polymer film (1) – cardboard packs.

Clinical-Pharmacological Group

Injectable corticosteroids

Pharmacotherapeutic Group

Glucocorticosteroid

Pharmacological Action

Corticosteroid. It has anti-inflammatory, anti-allergic, desensitizing, anti-shock, antitoxic, and immunosuppressive effects, and also has a pronounced and diverse effect on various types of metabolism.

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

It increases the excitability of the CNS, reduces the number of lymphocytes and eosinophils, and increases the number of erythrocytes (stimulates the production of erythropoietins).

It interacts with specific cytoplasmic receptors and forms a complex that penetrates the cell nucleus and stimulates the synthesis of mRNA; the latter induces the formation of proteins, including lipocortin, which mediate cellular effects. Lipocortin inhibits phospholipase A₂, suppresses the release of arachidonic acid, and inhibits the synthesis of endoperoxides, prostaglandins, leukotrienes, which contribute to the processes of inflammation and allergy.

The anti-inflammatory effect is associated with the inhibition of the release of inflammatory mediators by eosinophils; induction of lipocortin formation and reduction in the number of mast cells producing hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes and organelle membranes (especially lysosomal).

The anti-allergic effect develops as a result of suppression of the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, T- and B-lymphocytes, mast cells, reduction of effector cell sensitivity to allergy mediators, inhibition of antibody formation, and changes in the body’s immune response.

The anti-shock and antitoxic action is associated with an increase in blood pressure (due to an increase in the concentration of circulating catecholamines and restoration of sensitivity to them of adrenoreceptors, as well as vasoconstriction), a decrease in vascular wall permeability, membrane-stabilizing properties, and activation of liver enzymes involved in the metabolism of endo- and xenobiotics.

In COPD, the action is based mainly on the inhibition of inflammatory processes, suppression of the development or prevention of mucosal edema, inhibition of eosinophilic infiltration of the bronchial epithelium submucosal layer, deposition of circulating immune complexes in the bronchial mucosa, as well as on the inhibition of erosion and desquamation of the mucosa. It increases the sensitivity of beta-adrenoreceptors of small and medium caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, and reduces mucus viscosity by inhibiting or reducing its production.

The immunosuppressive effect is due to the inhibition of the release of cytokines ( interleukin-1, interleukin-2, interferon gamma) from lymphocytes and macrophages.

It suppresses the synthesis and secretion of ACTH and, secondarily, the synthesis of endogenous corticosteroids. It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

Protein metabolism: reduces the amount of protein in plasma (due to globulins) with an increase in the albumin/globulin ratio, increases the synthesis of albumins in the liver and kidneys; enhances protein catabolism in muscle tissue.

Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (accumulation of fat mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.

Carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract; increases the activity of glucose-6-phosphatase, leading to an increase in the release of glucose from the liver into the blood; increases the activity of phosphoenolpyruvate carboxykinase and the synthesis of aminotransferases, leading to the activation of gluconeogenesis.

Water-electrolyte metabolism: retains sodium and water in the body, stimulates the excretion of potassium, reduces the absorption of calcium from the gastrointestinal tract, “washes out” calcium from the bones, and increases renal excretion.

Betamethasone sodium phosphate is a readily soluble compound that is well absorbed after parenteral administration into tissues and provides a rapid effect.

Betamethasone dipropionate has slower absorption. Combining these salts makes it possible to create drugs with both short-term (but rapid) and long-term action. Depending on the method of application (intravenous, intramuscular, intra-articular, periarticular, intradermal), a general or local effect is achieved.

Pharmacokinetics

Betamethasone sodium phosphate is highly soluble in water and, after intramuscular injection, is rapidly hydrolyzed and absorbed almost immediately from the injection site, which ensures a rapid onset of therapeutic action. It is almost completely eliminated within one day after administration.

Betamethasone dipropionate is slowly absorbed from the depot, metabolized gradually, which determines its prolonged action, and is eliminated over more than 10 days.

The binding of betamethasone to plasma proteins is 62.5%. It is metabolized in the liver with the formation of predominantly inactive metabolites. It is excreted mainly by the kidneys.

Indications

Treatment in adults of conditions and diseases in which corticosteroid therapy can achieve the necessary clinical effect (it must be taken into account that for some diseases, corticosteroid therapy is additional and does not replace standard therapy): diseases of the musculoskeletal system and soft tissues, including rheumatoid arthritis, osteoarthritis, bursitis, ankylosing spondylitis, epicondylitis, coccydynia, torticollis, ganglion cyst, fasciitis; allergic diseases, including bronchial asthma, hay fever (pollinosis), allergic bronchitis, seasonal or perennial rhinitis, drug allergy, serum sickness, reactions to insect bites; dermatological diseases, including atopic dermatitis, nummular eczema, neurodermatitis, contact dermatitis, severe photodermatitis, urticaria, lichen planus, alopecia areata, discoid lupus erythematosus, psoriasis, keloid scars, pemphigus vulgaris, cystic acne; systemic connective tissue diseases, including systemic lupus erythematosus, scleroderma, dermatomyositis, polyarteritis nodosa; hemoblastoses (palliative therapy of leukemia and lymphoma in adults; acute leukemia in children); primary or secondary adrenal cortex insufficiency (with mandatory simultaneous use of mineralocorticosteroids).

Other diseases and pathological conditions requiring systemic corticosteroid therapy (adrenogenital syndrome, regional ileitis, pathological blood changes when corticosteroid use is necessary).

ICD codes

Dosage Regimen

Determine the dosage individually based on the specific disease, severity, and patient response.

Administer the suspension by deep intramuscular injection. Avoid intravenous, subcutaneous, intradermal, or epidural administration.

For most conditions in adults, the initial dose is 1-2 ml administered intramuscularly. The dosage depends on the clinical situation.

For severe conditions, a dose of 2 ml may be required. Repeat administration only upon symptom recurrence.

Do not administer more frequently than every 2-4 weeks due to the prolonged duration of action.

Use the lowest effective dose for the shortest possible duration to achieve the desired therapeutic effect.

Gradually taper the dose when discontinuing treatment after long-term therapy. Abrupt withdrawal is dangerous.

For intra-articular or periarticular use, dosage depends on the joint size. For large joints (e.g., knee, ankle), use 0.5-2.0 ml.

For medium-sized joints (e.g., elbow, wrist), use 0.25-0.5 ml. For small joints, use 0.125-0.25 ml.

Aseptically prepare the injection site. Ensure the suspension is uniformly mixed before withdrawal from the ampoule.

Do not mix Betaspan Depo with other injectable solutions in the same syringe, as this may alter its properties.

Monitor patients closely for both local and systemic adverse reactions, especially with repeated injections.

Adverse Reactions

Metabolism: hypernatremia, increased potassium excretion, increased calcium excretion, hypokalemic alkalosis, fluid retention in tissues, negative nitrogen balance (due to protein catabolism), lipomatosis (including mediastinal and epidural lipomatosis, which can cause neurological complications), weight gain.

Cardiovascular system: chronic heart failure (in predisposed patients), increased blood pressure.

Musculoskeletal system: muscle weakness, steroid myopathy, loss of muscle mass, increased myasthenic symptoms in severe pseudoparalytic myasthenia, osteoporosis, compression fracture of the spine, aseptic necrosis of the femoral or humeral head, pathological fractures of long bones, tendon ruptures, joint instability (with repeated intra-articular injections).

Digestive system: erosive-ulcerative lesions of the gastrointestinal tract with possible subsequent perforation and bleeding, pancreatitis, flatulence, hiccups.

Dermatological reactions: impaired wound healing, atrophy and thinning of the skin, petechiae, ecchymoses, increased sweating, dermatitis, steroid acne, striae, tendency to develop pyoderma and candidiasis, reduced response during skin tests.

Nervous system: convulsions, increased intracranial pressure with papilledema (more often at the end of therapy) dizziness, headache, euphoria, mood changes, depression (with pronounced psychotic reactions), personality disorders, increased irritability, insomnia.

Endocrine system: menstrual cycle disorders, secondary adrenal insufficiency (especially during stress in illness, trauma, surgery), Cushing’s syndrome, decreased carbohydrate tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, increased need for insulin or oral hypoglycemic drugs, impaired intrauterine development, growth retardation and sexual development in children.

Organ of vision: posterior subcapsular cataract, increased intraocular pressure, glaucoma, exophthalmos; in rare cases – blindness (when the drug is administered in the face and head area).

Allergic reactions: anaphylactic reactions, shock, angioedema, arterial hypotension.

Local reactions: rarely – hyper- or hypopigmentation, subcutaneous and cutaneous atrophy, aseptic abscesses.

Other: facial flushing after injection (or intra-articular administration), neurogenic arthropathy.

The frequency of development and severity of side effects, as with the use of other corticosteroids, depend on the dose used and the duration of drug use. These phenomena are usually reversible and can be eliminated or reduced by reducing the dose.

Contraindications

For short-term use for vital indications, the only contraindication is hypersensitivity; intravenous, subcutaneous, epidural, intrathecal administration; administration directly into muscle tendons; coagulation disorders (including treatment with anticoagulants), cerebral edema due to traumatic brain injury; breastfeeding period, simultaneous administration of immunosuppressive doses with live and attenuated vaccines.

For intra-articular administration: 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 a 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 an outcome of arthritis, aseptic necrosis of the bone epiphyses forming the joint; administration into the intervertebral space.

With caution

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; amoebiasis, strongyloidiasis (established or suspected); systemic mycosis; active and latent tuberculosis. Use in severe infectious diseases is permissible only against the background of specific therapy.

Post-vaccination period (a period of 8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination. Immunodeficiency states (including AIDS or HIV infection).

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.

Cardiovascular system diseases: recent myocardial infarction (in patients with acute and subacute myocardial infarction, the spread of the necrosis focus, slowing of scar tissue formation, and, as a result, rupture of the heart muscle are possible), decompensated chronic heart failure, arterial hypertension, hyperlipidemia.

Endocrine diseases: diabetes mellitus (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Cushing’s disease.

Severe chronic renal and/or hepatic insufficiency, nephrourolithiasis.

Hypoalbuminemia and conditions predisposing to its occurrence.

Systemic osteoporosis, myasthenia gravis, acute psychosis, obesity (grade III-IV), poliomyelitis (except for the form of bulbar encephalitis), open-angle and angle-closure glaucoma, pregnancy, lactation period.

For intra-articular administration: patient’s general severe condition, ineffectiveness (or short duration) of the action of 2 previous injections (taking into account the individual properties of the glucocorticosteroids used).

Use in Pregnancy and Lactation

Use during pregnancy is not recommended.

Betamethasone crosses the placental barrier. Animal studies have recorded fetal malformations and developmental disorders (delays) with the use of glucocorticosteroids during pregnancy.

With long-term or repeated use of glucocorticosteroids during pregnancy, the risk of intrauterine growth retardation may increase. Cases of myocardial hypertrophy and gastroesophageal reflux have been reported in newborns when betamethasone was used during pregnancy.

Newborns whose mothers received therapeutic doses of glucocorticosteroids during pregnancy should be under medical supervision (for early detection of signs of adrenal insufficiency).

Contraindicated for use during lactation (breastfeeding).

Special Precautions

This medicinal product should be used at the lowest effective dose for the minimum duration. The initial dose is adjusted until the desired therapeutic effect is achieved. Then the dose is gradually reduced to the minimum effective maintenance dose. If there is no effect from the therapy or after its long-term use, discontinuation is carried out gradually by reducing the dose. The patient’s condition should be monitored for at least one year after the end of long-term therapy or use in high doses.

If a stressful situation arises or is threatened (not related to the disease), it may be necessary to increase the dose.

Administration of the drug into soft tissues, into the lesion, and intra-articularly, while having a pronounced local effect, can simultaneously lead to a systemic effect.

When used in patients with diabetes mellitus, adjustment of hypoglycemic therapy may be required.

Patients receiving glucocorticosteroids should not be vaccinated against smallpox. Other immunization should not be carried out in patients receiving glucocorticosteroids (especially in high doses!), due to the possibility of developing neurological complications and a low immune response (“lack of antibody formation”). However, immunization is possible when carrying out replacement therapy (for example, in primary adrenal cortex insufficiency).

Patients receiving this combination in immunosuppressive doses should be warned to avoid contact with patients with chickenpox and measles (especially important when using the drug in children).

Suppression of the reaction during skin tests while using glucocorticosteroids is possible. It should be taken into account that glucocorticosteroids can mask the signs of an infectious disease and also reduce the body’s resistance to infections.

Suppression of the reaction during skin tests while using glucocorticosteroids is possible.

The effect of glucocorticosteroids is enhanced in patients with hypothyroidism and liver cirrhosis.

Caution should be exercised when using glucocorticosteroids in elderly patients; in patients with renal or hepatic insufficiency, diverticulitis, active or latent gastric and/or intestinal ulcer disease or with recently created intestinal anastomoses, osteoporosis, myasthenia gravis, confirmed or suspected parasitic infections (e.g., strongyloidiasis).

The development of secondary adrenal cortex insufficiency due to too rapid withdrawal of glucocorticosteroids is possible for several months after the end of therapy.

While using glucocorticosteroids, changes in sperm motility and count are possible. With long-term glucocorticosteroid therapy, it is advisable to consider the possibility of switching from parenteral to oral administration of glucocorticosteroids, taking into account the benefit/risk assessment.

Use in pediatrics

Children undergoing therapy (especially long-term) with a drug containing this combination should be under careful medical supervision for possible growth retardation and development of secondary adrenal cortex insufficiency.

Use in athletes

Patients participating in competitions under the control of the World Anti-Doping Agency (WADA) should familiarize themselves with the WADA rules before starting treatment with a drug containing this combination, as the use of such drugs may affect the results of doping control.

Drug Interactions

With simultaneous use of phenobarbital, rifampicin, phenytoin, or ephedrine, acceleration of betamethasone metabolism with a decrease in its therapeutic activity is possible.

With simultaneous use of glucocorticosteroids and estrogens, dose adjustment of betamethasone may be required (due to the risk of overdose).

With concomitant use of betamethasone and potassium-excreting diuretics, the likelihood of hypokalemia increases.

Simultaneous use of glucocorticosteroids and cardiac glycosides increases the risk of arrhythmia or digitalis intoxication (due to hypokalemia). Betamethasone may enhance potassium excretion caused by amphotericin B.

With concomitant use of betamethasone and indirect anticoagulants, changes in blood coagulability are possible, requiring adjustment of the anticoagulant dose.

With combined use of glucocorticosteroids with NSAIDs or with ethanol and ethanol-containing drugs, an increase in the frequency or intensity of erosive and ulcerative lesions of the gastrointestinal tract is possible.

With concomitant use, glucocorticosteroids may reduce the plasma concentration of salicylates.

Simultaneous administration of glucocorticosteroids and somatotropin may lead to slower absorption of the latter (administration of betamethasone doses exceeding 300-450 mcg/m²/day should be avoided).

Glucocorticosteroids may affect the nitroblue tetrazolium test for bacterial infection and cause a false-negative result.

Aminoglutethimide may reduce the corticosteroid-induced suppression of adrenal function.

With simultaneous use of glucocorticosteroids and ketoconazole or itraconazole, an increase in the systemic side effects of glucocorticosteroids is possible.

Glucocorticosteroids can reduce the effect of cholinesterase inhibitors, which can lead to the development of severe muscle weakness in patients with myasthenia gravis. If possible, cholinesterase inhibitors should be discontinued at least 24 hours before starting glucocorticosteroid therapy.

With simultaneous use of glucocorticosteroids and isoniazid, a decrease in the plasma concentration of isoniazid is possible. The condition of patients taking isoniazid should be carefully monitored.

Simultaneous use of cyclosporine and glucocorticosteroids may lead to an increase in cyclosporine concentration and enhancement of the effect of glucocorticosteroids. There is a high risk of seizures.

With simultaneous use of glucocorticosteroids with macrolide antibiotics, a significant decrease in the excretion of glucocorticosteroids is possible.

With simultaneous use with cholestyramine, an increase in the excretion of glucocorticosteroids is possible.

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.