Betaspan solution for injection 4 mg/ml ampoule 1 ml No. 5

Instructions Betaspan solution for injection 4 mg/ml ampoule 1 ml No. 5

Composition

active ingredient: betamethasone;

1 ml of solution contains betamethasone sodium phosphate – 5.3 mg, calculated as betamethasone 100% substance – 4 mg;

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

Dosage form

Solution for injection.

Main physicochemical properties: transparent colorless solution.

Pharmacotherapeutic group

Corticosteroids for systemic use. Glucocorticoids. Betamethasone. ATC code H02A B01.

Pharmacological properties

Pharmacodynamics

Betamethasone is a synthetic glucocorticoid drug for systemic use. It has a pronounced anti-inflammatory, antirheumatic and antiallergic effect in the treatment of diseases that respond to corticosteroid therapy. It modifies the body's immune reactions. Betamethasone has high glucocorticosteroid activity and weak mineralocorticoid activity.

Pharmacokinetics

Betamethasone is rapidly absorbed from the injection site. The maximum concentration in blood plasma is reached after 1 hour. Betamethasone is almost completely excreted within 1 day. Biotransformed in the liver. The half-life is 300 minutes or more. In patients with liver diseases, betamethasone clearance is slower. Binding to plasma proteins is high. It has been studied that clinical efficacy depends more on the level of the unbound fraction of the corticosteroid than on the total plasma concentration. There is no relationship between the level of corticosteroid in blood plasma and the duration of the therapeutic effect. Easily overcomes the placental, blood-brain and other histohematological barriers, penetrates into breast milk. Excreted by the kidneys.

Indication

In the treatment of various endocrine, rheumatic diseases, collagen diseases, dermatological, allergic, ophthalmological, gastrointestinal, respiratory, hematological and other diseases that respond to corticosteroid therapy. Corticosteroid hormone therapy is adjunct to traditional therapy and is not a substitute. This drug is indicated when a rapid, intense corticosteroid effect is necessary or desired. Betaspan® is intended for a rapid and powerful therapeutic effect.

Endocrine diseases: 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 diseases) in known or suspected adrenal insufficiency; shock unresponsive to conventional therapy when adrenocortical insufficiency is suspected; bilateral adrenalectomy; congenital adrenal hyperplasia; acute thyroiditis, non-suppurative thyroiditis and thyroid crisis; hypercalcemia associated with cancer.

Cerebral edema (increased intracranial pressure): The clinical benefit of concomitant corticosteroid therapy in cerebral edema is likely to be achieved by suppression of cerebral inflammation. Corticosteroids should not be considered a substitute for neurosurgery. They are helpful in reducing or preventing cerebral edema associated with surgical and other brain trauma, cerebrovascular events, and primary or metastatic brain tumors.

Cases of renal allograft rejection: the drug has been shown to be effective in the treatment of acute primary rejection and classic delayed rejection in combination with conventional therapy for the prevention of renal transplant rejection.

Prenatal use to prevent respiratory distress syndrome in premature infants: The drug is indicated for the prophylactic treatment of hyaline membrane disease in premature infants when administered to mothers (up to 32 weeks of gestation) before delivery.

Musculoskeletal disorders: as adjunctive therapy for short-term use (to relieve acute conditions 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 tendosynovitis; myositis; calluses. Treatment of cystic tumors of the aponeurosis or tendon (ganglion).

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

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

Ophthalmological diseases: severe, acute and chronic allergic and inflammatory processes in the eyes and adjacent tissues, such as allergic conjunctivitis, keratitis, allergic marginal corneal ulcers, ocular herpes zoster, iritis and iridocyclitis, chorioretinitis, anterior segment inflammation, diffuse posterior uveitis and choroiditis, optic neuritis; sympathophthalmia.

Respiratory diseases: symptomatic sarcoidosis; untreated Leffler syndrome; berylliosis; fulminant and disseminated pulmonary tuberculosis (accompanied by specific anti-tuberculosis therapy); aspiration pneumonia.

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

Gastrointestinal tract diseases: nonspecific ulcerative colitis; regional enteritis.

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

Edema: to increase the induction of diuresis or remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or in systemic lupus erythematosus.

Other: tuberculous meningitis with subarachnoid blockade or its threat against the background of specific anti-tuberculosis chemotherapy; trichinellosis with neurological and myocardial lesions.

Contraindication

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

Peptic ulcer disease of the stomach and duodenum.

Acute infectious processes: viral infections and systemic fungal infections.

Tropical parasitic infections.

After vaccination with live attenuated viruses.

Special safety precautions

Strict adherence to asepsis rules is mandatory when using the drug.

Interaction with other medicinal products and other types of interactions

Concomitant use of phenobarbital, rifampicin, phenytoin, or ephedrine may accelerate the metabolism of corticosteroids, leading to a weakening of the therapeutic effect.

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

Concomitant use of corticosteroids and potassium-sparing diuretics may cause hypokalemia.

The combined use of corticosteroids with cardiac glycosides may increase the likelihood of arrhythmias or enhance glycoside toxicity associated with hypokalemia.

Corticosteroids may enhance the potassium excretion caused by amphotericin B. Serum electrolyte concentrations, especially potassium, should be closely monitored in all patients receiving either combination. Concomitant use of corticosteroids with indirect anticoagulants may result in either potentiation or attenuation of the anticoagulant effect, which may require dose adjustment.

The combined effect of nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol with glucocorticosteroids may lead to an increase in the frequency or severity of gastrointestinal ulcers.

When using corticosteroids, the concentration of salicylates in the blood may decrease. Acetylsalicylic acid should be used with caution in combination with corticosteroids in hypoprothrombinemia.

When administering corticosteroids to patients with diabetes, dose adjustments of antidiabetic agents may be required.

Glucocorticosteroid treatment may reduce the response to somatotropin. Betamethasone doses greater than 300–450 mcg (0.3–0.45 mg) per m2 of body surface area per day should be avoided during the period of somatotropin administration.

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

Application features

Serious neurological events, some of which were fatal, have been reported following epidural corticosteroid injections. Spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke have also been reported. These serious neurological events have occurred regardless of the use of fluoroscopy. Because the safety and efficacy of epidural injections have not been established, corticosteroids are not recommended for epidural use.

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

Intra-articular fluid should be examined to rule out septicemia. Local injections into a previously infected joint should be avoided. Marked increase in pain and local swelling, subsequent limitation of joint motion, 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 injections into joints with osteoarthritis may increase joint destruction. Direct injection of corticosteroids into tendons should be avoided as this may result in delayed tendon rupture.

After intra-articular betamethasone therapy, the patient should avoid very heavy loads on the joint in which the symptoms have been relieved.

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

When using long-term corticosteroid therapy, all potential benefits and risks should be considered before switching from parenteral to oral administration.

Changes in the dosage regimen are possible according to the course of the disease during remission or exacerbation, the patient's response to therapy, negative changes in the patient's emotional and physical state, for example, severe infection, surgery or trauma. After completing a long or intensive course of glucocorticosteroid treatment, constant monitoring of the patient's condition is required for a year.

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

Corticosteroids may mask signs of infections or new infections may occur while taking corticosteroids. Corticosteroids reduce the body's resistance and ability to localize infection.

With long-term use, posterior subcapsular cataracts may occur (especially in children), glaucoma with possible damage to the optic nerve, and an increased risk of secondary fungal or viral eye infections. Periodic ophthalmological examinations should be performed, especially in patients on long-term therapy (more than 6 weeks).

Moderate to high doses of corticosteroids may cause elevations in blood pressure, salt and fluid retention, and increased potassium excretion. These effects are less likely with synthetic derivatives (but not with high doses). However, a salt-restricted diet and potassium supplements may be necessary. All corticosteroids increase calcium excretion.

Patients receiving corticosteroids should not be vaccinated against varicella. Patients receiving corticosteroids, especially high doses, should not be vaccinated against other infections because of the risk of neurological complications and reduced immune response. However, immunization is possible in patients receiving corticosteroids as replacement therapy, for example, for Addison's disease.

Patients receiving immunosuppressive doses of corticosteroids should avoid contact with people with chickenpox and measles. This is especially important for children.

In active tuberculosis, corticosteroid therapy should be limited to cases of fulminant or disseminated tuberculosis, in which the corticosteroid is used only in conjunction with antituberculosis therapy. Patients with latent tuberculosis or those with tuberculin reactivity who are receiving corticosteroids should be under medical supervision because reactivation of the disease is possible. Patients should receive chemoprophylaxis during prolonged corticosteroid therapy. If rifampicin is used as part of chemotherapy, its enhancing effect on the metabolic hepatic clearance of corticosteroids should be considered; corticosteroid dosage may need to be adjusted.

To control the condition, the lowest dose of corticosteroid should be used during treatment; if possible, the dose should be reduced gradually.

If corticosteroid is withdrawn too rapidly, secondary adrenal insufficiency may occur, which may be minimized by gradual dose reduction. This relative insufficiency may persist for several months after discontinuation of therapy; therefore, if the patient experiences a stressful situation during this period, corticosteroid therapy should be resumed. If the patient is already receiving corticosteroids, the dosage may need to be increased. Salt and/or mineralocorticoids should be used concomitantly because of possible impairment of mineralocorticoid secretion. Dose reduction should be performed under close medical supervision, and it may be necessary to monitor the patient for up to one year after discontinuation of prolonged treatment or increased doses.

Betamethasone should only be used by diabetics for a short period of time and only under strict medical supervision, given its glucocorticoid properties (transformation of proteins into glucose).

The effect of the drug is enhanced in people with hypothyroidism and liver cirrhosis.

During corticosteroid therapy, mental disorders may occur (especially in patients with emotional instability or a tendency to psychosis).

The drug should be used with caution in nonspecific ulcerative colitis with the threat of perforation, abscess or other purulent infection, diverticulitis, intestinal anastomosis, gastric and duodenal ulcer, renal failure, arterial hypertension, osteoporosis, myasthenia gravis, glaucoma, acute psychoses, viral and bacterial infections, growth retardation, tuberculosis, Cushing's syndrome, diabetes, heart failure, in cases of difficult-to-treat epilepsy, predisposition to thromboembolism or thrombophlebitis, during pregnancy.

Complications of glucocorticosteroid treatment depend on the dose and duration of treatment, so it is necessary to consider the risk/benefit ratio for each patient.

In some patients, corticosteroids may cause a decrease in sperm count and motility.

Pheochromocytoma crisis, including fatal cases, has been reported. Corticosteroids should be administered to patients with known or suspected pheochromocytoma only after appropriate benefit-risk assessment.

Results from one multicenter randomized controlled trial with another corticosteroid (methylprednisolone hemisuccinate) showed an increase in early mortality (at 2 weeks) and late mortality (at 6 months) in patients with traumatic brain injury who received methylprednisolone compared with placebo. The causes of mortality in the methylprednisolone group were not determined. It should be noted that this trial did not include patients who had a direct indication for corticosteroids. High doses of corticosteroids should not be used to treat traumatic brain injury.

The total amount of sodium in 1 ml of solution is 0.06 mmol, i.e. the drug is practically sodium-free.

Use during pregnancy or breastfeeding

The safety of the drug during pregnancy has not been established, therefore Betaspan® should be used during this period only if the expected benefit to the mother outweighs the possible risk to the fetus.

The question of the feasibility of antenatal prophylaxis of distress syndrome after the 32nd week of pregnancy has not been conclusively studied. Therefore, physicians should assess the benefit/risk ratio for the mother and fetus when using corticosteroids after the 32nd week of pregnancy.

Corticosteroids should not be prescribed for the treatment of hyaline membrane disease in the first days after birth.

To prevent hyaline membrane disease in premature infants, corticosteroids should not be administered to women with placental damage or to women with preeclampsia or eclampsia.

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

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

Since corticosteroids pass transplacentally, newborns and infants born to mothers who received corticosteroids during pregnancy should be closely monitored for the very rare occurrence of congenital cataracts.

Women who have received corticosteroids during pregnancy should be under special supervision during and after delivery due to the possibility of adrenocortical insufficiency (due to the stress of childbirth).

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

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

Ability to influence reaction speed when driving vehicles or other mechanisms

Betaspan® does not affect the patient's reaction speed when driving or using other mechanisms.

But in rare cases, muscle weakness, cramps, dizziness, headache, psychoemotional instability, severe depression up to the appearance of frank psychotic reactions, irritability may occur, therefore it is recommended to refrain from driving or other mechanisms during treatment with the drug.

Method of administration and doses

Betaspan® can be administered intravenously, intramuscularly, intraarticularly, into lesion sites, as well as into soft tissues.

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

For children, the usual starting intramuscular dose of betamethasone is 20–125 mcg/kg/day. Dosage for younger and older children should be based on the same principles as for adults (with preference given to strictly adhering to the dosages indicated for age and body weight).

Although Betaspan® can be administered by several routes, intravenous administration is recommended in emergency situations.

Betaspan® should be administered intravenously by drip with 0.9% sodium chloride or glucose solution. Betaspan® should be added to the infusion solution during administration. Unused solution should be stored in the refrigerator and used within 24 hours.

After achieving a positive clinical effect, the initial dose should be gradually reduced at certain intervals until the lowest dose is reached, which allows maintaining the desired clinical result.

The occurrence of stressful situations in a patient (not related to his disease) may require an increase in the dose of Betaspan®.

When discontinuing the drug after long-term use, the dose should be reduced gradually.

Cerebral edema. Improvement of the patient's condition occurs within a few hours after the administration of 2-4 mg of betamethasone. For patients in a coma, the average single dose is 2-4 mg 4 times a day.

Renal allograft rejection reactions. At the first signs and diagnosis of acute or delayed rejection, Betaspan® should be administered intravenously by drip, the initial dose of betamethasone is 60 mg during the first 24 hours. Small individual dose changes are possible.

Antenatal prevention of respiratory distress syndrome in premature newborns. When stimulating labor before 32 weeks of gestation or when premature birth is inevitable before 32 weeks of gestation due to obstetric complications, it is recommended during

24–48 hours before the expected time of delivery, administer 4–6 mg of betamethasone intramuscularly every 12 hours (2–4 doses). Treatment should be started at least 24 hours (and preferably 48–72 hours) before delivery to allow sufficient time for the corticosteroid to take effect and for a reliable clinical outcome.

Betaspan® can also be used prophylactically if the amniotic fluid lecithin/sphingomyelin ratio is reduced (or the stability of the amniotic fluid foam test is reduced). When determining the dose in such cases, the above recommendations should be followed, including those regarding the timing of administration before delivery.

Musculoskeletal injuries, soft tissue diseases

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

Subconjunctival injection is usually 0.5 ml of the drug (2 mg of betamethasone).

Children.

During long-term treatment of infants and children, it is necessary to monitor their growth and development (given the possibility of growth suppression and endogenous corticosteroid production).

Children receiving immunosuppressive doses of corticosteroids should avoid contact with people with chickenpox and measles.

Overdose

Acute overdose of corticosteroids, including betamethasone, is not expected to be life-threatening. Except in very large doses, excessive use of corticosteroids is unlikely to cause adverse effects unless there are specific contraindications, such as diabetes, glaucoma, active peptic ulcer disease, and the patient is not taking digitalis, coumarin anticoagulants, or potassium-sparing diuretics.

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

Adequate fluid intake and monitoring of serum and urinary electrolyte levels, with particular attention to sodium and potassium balance, should be considered. Electrolyte balance should be restored if necessary.

Side effects

The frequency and severity of adverse events (as with all glucocorticoids) depend on the dose and duration of therapy. These events are usually reversible or minimized by reducing the dose, which is an advantage over drug withdrawal.

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

On the part of the psyche: euphoria, psychoemotional instability, mood swings, severe depression up to the appearance of frank psychotic reactions, particularly in patients with a psychiatric history, personality changes, increased irritability, insomnia.

On the part of the organs of vision: subcapsular posterior cataract, increased intraocular pressure, glaucoma, exophthalmos.

On the part of the endocrine system: secondary adrenocortical and pituitary insufficiency (especially during stress - injuries, surgery, diseases), reduced tolerance to carbohydrates, manifestation of latent diabetes, increased need for insulin and oral hypoglycemic agents in patients with diabetes, menstrual disorders, development of Cushingoid state with hirsutism, striae and acne, suppression of fetal growth or growth of children.

Metabolic: negative nitrogen balance (due to protein catabolism), lipomatosis, including mediastinal lipomatosis and epidural lipomatosis, which can cause neurological complications, weight gain. Fluid and electrolyte imbalance may also be observed in the form of: sodium retention in the body, potassium loss, hypokalemic alkalosis, increased calcium excretion, fluid retention in the body, congestive heart failure in susceptible patients, arterial hypertension.

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

On the part of the digestive system: hiccups, erosive-ulcerative lesions of the stomach with possible subsequent perforation and bleeding, esophageal ulcers, pancreatitis, flatulence, 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, angioedema.

Immune system: Corticosteroids may interfere with skin test results, mask symptoms of infection and activate latent infections, and reduce resistance to infections, particularly mycobacteria, Candida albicans and viruses. Anaphylactoid or hypersensitivity reactions and hypotensive or shock-like reactions.

In addition, adverse reactions associated with parenteral corticosteroid therapy include isolated cases of treatment-related blindness in the face and scalp, pigmentation disorders, cutaneous and subcutaneous atrophy, sterile abscesses, post-injection inflammation (after intra-articular administration), and Charcot-type arthropathy.

Secondary suppression of the pituitary gland and adrenal cortex in the event of stress (injury, surgery, or illness).

After repeated intra-articular injection, joint damage is possible. There is a risk of infection.

Expiration date

2 years.

Do not use the drug after the expiration date indicated on the package.

Storage conditions

Store in original packaging at a temperature not exceeding 25 ° C. Do not freeze.

Keep out of reach of children.

Packaging

1 ml in an ampoule; 1 or 5 ampoules in a pack.

1 ml in an ampoule; 5 ampoules in a blister; 1 blister in a pack.

Vacation category

According to the recipe.

Producer

JSC "Farmak".

Location of the manufacturer and its business address

Ukraine, 04080, Kyiv, Kyrylivska St., 74.