Rebospan

BRAND NAME:

Rebospan

INTERNATIONAL NONPROPRIETARY NAME

Betamethasone

DRUG FORM: suspension for injection

Description: Slightly viscous liquid with white particles free of related substances.

COMPOSITION:

1 ml of suspension contains:

Active ingredients: betamethasone dipropionate 6.43 mg (equivalent to 5 mg betamethasone), betamethasone sodium phosphate 2.63 mg (equivalent to 2 mg betamethasone).

PHARMACOTHERAPEUTIC CATEGORY:

Systemic Corticosteroids

ATC code: H02AB01.

PHARMACOLOGICAL PROPERTIES

PHARMACODYNAMICS:

Rebospan is a synthetic glucocorticosteroid (GCS) with high glucocorticoid and negligible mineralocorticoid activity. The drug possesses antiinflammatory, antiallergic and immunosuppressive effects and also regulates carbohydrate homeostasis and water-electrolyte balance.

Betamethasone does not have clinically significant mineralocorticoid effect. In addition to antiinflammatory and immune processes activation glucocorticoids also affect carbohydrates, proteins and lipids metabolism. In addition, glucocorticoids affect the cardiovascular system, skeletal muscles and the central nervous system.

Influence on inflammatory and immune processes. The antiinflammatory, immunosuppressive and antiallergic properties of glucocorticoids are important when used in therapeutic practice. The main results of these properties are: the decrease in quantity of immunoactive cells in the inflammatory site, the decrease in vasodilation, lysosomal membranes stabilization, phagocytosis suppression, and decrease in prostaglandins and related substances production. The drug antiinflammatory activity is approximately 25 times higher than that of hydrocortisone and 8-10 times higher than that of prednisolone (in a weight ratio).

Influence on carbohydrate and protein metabolism. Glucocorticoids stimulate protein catabolism. As a result of gluconeogenesis in the liver the released amino acids are converted into glucose and glycogen. Peripheral tissue glucose absorption is reduced, leading to hyperglycemia and glycosuria, especially in patients predisposed to diabetes.

Influence on lipid metabolism. Glucocorticoids demonstrate lipolytic effect. Lipolysis is mostly observed in extremities. In addition, glucocorticoids affect lipogenesis mostly manifested in the truncal, neck and head area. For a total these effects lead to a redistribution of lipid deposits.

PHARMACOKINETICS:

Betamethasone sodium phosphate and betamethasone dipropionate are absorbed at the injection site, providing rapid therapeutic effect as well as other local and general pharmacological effects.

Betamethasone sodium phosphate is rapidly dissolved in water and metabolized in the body to betamethasone (the biologically active glucocorticoid). 2.63 mg of betamethasone sodium phosphate is equivalent to 2 mg of betamethasone.

Betamethasone dipropionate administration provides prolongation of the drug action. This substance is practically insoluble, representing a depot, so absorption slows down and symptomatic relief lasts longer.

Betamethasone is metabolized in the liver. It binds mainly with albumin. In patients with liver diseases betamethasone metabolism is longer or slower in time period.

INDICATIONS FOR USE:

Corticosteroid therapy is supportive and does not replace conventional treatment.

Intramuscular administration: Rebospan is indicated for the treatment of various rheumatological, dermatological, allergic, systemic diseases of connective tissue and other diseases usually treatable with corticosteroids.

Intra-articular and periarticular administration as well as the direct injection into the soft tissue: additional short-term therapy (in acute form of disease or its exacerbation) in osteoarthritis and rheumatoid arthritis.

Intradermal administration: in dermatological diseases.

Local injection into the foot tissue: additional short-term therapy (in acute form of current disease or its exacerbation) in case of bursitis hard callus, bone spur, stiffness or deformity of the big toe, with synovial cyst, Morton metatarsal neuralgia, tenosynovitis, periostitis of the cuboid bone.

Allergic conditions: bronchial asthma, asthmatic status, seasonal or perennial allergic rhinitis, severe allergic bronchitis, contact dermatitis, atopic dermatitis, hay fever, angioedema, serum sickness, hypersensitivity reactions to drugs or insect bites.

Rheumatic diseases: osteoarthritis, rheumatoid arthritis, bursitis, lumbago, sciatica, coccidinia, acute gouty arthritis, torticollis, ganglion cyst, ankylosing spondylitis, radiculitis, exostosis, fasciitis.

Dermatological diseases: atopic dermatitis (coin-shaped eczema), neurodermatitis (Vidal's disease), contact dermatitis, pronounced solar dermatitis, urticaria, hypertrophic lichen planus, lipoid diabetic necrobiosis, alopecia areata, discoid lupus erythematosus, psoriasis, vermicelliformis dermatitis, cystic acne.

Connective tissue systemic diseases: in exacerbation or as a supportive treatment for certain types of disseminated systemic lupus erythematosus, polyarteritis nodosa, systemic sclerosis and dermatomyositis.

Oncological diseases: palliative therapy of leukemia and lymphoma in adults and acute leukemia in children.

Other conditions: adrenogenital syndrome, hemorrhagic rectocolitis, Crohn’s disease, celiac disease, pathological changes in blood required glucocorticoid therapy, nephritis, nephrotic syndrome.

In primary or secondary insufficiency of adrenal cortex Rebospan can be chosen for treatment, however, mineralocorticoids can be used at a time.

CONTRAINDICATIONS:

- hypersensitivity to the drug components or to other corticosteroids;

- systemic mycoses;

- intra-articular administration: unstable joint, infectious arthritis;

- intramuscular administration in patients with idiopathic thrombocytopenic purpura.

SIDE EFFECT:

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

Musculoskeletal system disorders: muscle weakness, steroid myopathy, loss of muscle mass.

Gastrointestinal system disorders: erosive and ulcerative lesions of gastrointestinal tract with possible subsequent perforation and bleeding, pancreatitis, flatulence, nausea, vomiting.

Central nervous system disorders: convulsions, increased intracranial pressure with the optic disk swelling (usually after treatment), dizziness, headache, euphoria, mood changes, depression (with severe psychotic reactions), increased irritability and insomnia.

Endocrine system disorders: loss of a cycle, Itsenko-Cushing's syndrome, carbohydrate tolerance decrease, steroid diabetes mellitus or latent diabetes mellitus manifestation, greater demand for insulin or oral hypoglycemic drugs.

Skin disorders: wound healing disorder, skin atrophy and thinning, petechiae, ecchymosis, excessive sweating, dermatitis, rash, urticaria.

Immune system disorders: corticosteroids can inhibit skin tests, mask the symptoms of infection and activate latent infection and reduce resistance to infectious pathogens in particular mycobacteria (with tuberculosis), Candida albicans and viruses.

Allergic reactions: anaphylactic reactions, shock, angioedema, blood pressure decrease.

DOSAGE AND ADMINISTRATION

It is prohibited to inject Rebospan intravenously or subcutaneously!

Before use the ampoule should be shaken.

THE DOSE IS SELECTED INDIVIDUALLY AND DEPENDS ON THE PATIENT’S NEEDS, THE DISEASE, SEVERITY AND THE PATIENT'S RESPONSE.

Systemic use

In systemic therapy the initial drug dose in most cases is 1-2 ml. The dose can be repeated when necessary. The drug injection is performed deep intramuscular into the buttock. In case of serious diseases when emergency treatment is necessary, for example, in systemic lupus erythematosus or asthmatic status the initial drug dose can be 2 ml.

In various dermatological diseases the good response is usually achieved after intramuscular injection of 1 ml of Rebospan; the dose can be repeated depending on the therapeutic effect.

In respiratory system disorders symptom relief is achieved several hours after the intramuscular injection of Rebospan. In case of bronchial asthma, hay fever, allergic bronchitis and allergic rhinitis effective control of the symptoms is achieved after injection of 1-2 ml dose.

In case of acute or chronic bursitis effective results are achieved after a single intramuscular injection of 1-2 ml of Rebospan. If necessary the injection can be repeated.

Local administration

Concomitant use of local anesthetic drug is necessary only in limited cases (the injection is almost painless). When simultaneous administration of anesthetic is needed Rebospan can be mixed (in a syringe, not in a vial) with 1% or 2% lidocaine hydrochloride solution, procaine hydrochloride or similar local anesthetics using paraben-free dosage forms. It is prohibited to use anesthetics containing methylparaben, propylparaben, phenol and other similar substances. Firstly, the required dose of Rebospan should be taken into syringe from the vial; then the required amount of local anesthetic should be taken into the same syringe and shaken for a short run.

In case of acute bursitis (subdeltoid, subacromial and prepatellar): the injection of 1-2 ml of Rebospan directly into the synovial bag can relieve pain and completely restore mobility within a few hours.

In chronic bursitis treatment: in case of good result in emergency treatment the drug dose can be reduced.

In case of tendinitis, tendosynovitis and peritendinitis treatment: in the acute stage of disease single injection can be enough to improve patient’s condition, in chronic – it may require repeated injection depending on the patient’s condition.

In case of rheumatoid arthritis and osteoarthritis treatment: usually intra-articular injection of 0.5–2 ml drug dose reduces the pain, stiffness and pain in joints – within 2-4 hours after injection. The therapeutic effect duration varies significantly in these diseases and can last for 4 or more weeks.

Intra-articular Rebospan injection is well tolerated and highly effective for treating joints and periarticular tissue.

Recommended doses of the drug:

- When injected into large joints (e.g. knee, hip): 1-2 ml;

- When introduced into middle joints (e.g. elbow): 0.5-1 ml;

- When introduced into small joints (e.g. joints of the hand): 0.25-0.5 ml.

For skin diseases treatment: in dermatological diseases Rebospan is effective when injected directly into the lesion. Positive effect on some lesion sites treatment where the drug is not applied directly may be associated with a minor systemic effect of the drug.

Single dose is 0.2 ml/cm2. The drug should be administered intradermally (not subcutaneously) using a tuberculin syringe with a 26G needle. The total amount of the drug injected into all the affected areas should not exceed 1 ml.

In foot disorders treatable by glucocorticoid therapy: bursitis with calluses, two consecutive injections of 0.25 ml (each injection) can be effective. In other diseases treatment, such as the big toe stiffness (Hallux Rigidus), the fifth toe varus deformity and acute gouty arthritis the improvement can be achieved very quickly. 25G needle tuberculin syringe, 1.9 cm length is suitable for most foot injections. Recommended doses (with 1 week intervals between the doses) are the following:

Bursitis treatment:

- callus treatment                                – 0, 25-0.5 ml;

- bone spur treatment                           – 0.5 ml;

- big toe stiffness treatment                 – 0.5 ml;

- varus deformity of the fifth toe         – 0.5 ml;

Synovial cyst treatment                       – 0.25-0.5 ml;

Morton’s metatarsal neuralgia             – 0.25-0.5 ml;

Tendosynovitis treatment                    – 0.5 ml;

Cuboid bone periostitis                       – 0.5 ml;

Acute gouty arthritis                           – 0.5 - 1 ml;

PRECAUTIONARY MEASURES:

Rebospan should not be administered intravenously or subcutaneously!

Serious neurological reactions (sometimes fatal) have been reported with epidural injection of corticosteroids. Safety and efficacy of corticosteroids epidural administration have not been established therefore this route of administration is prohibited.

The injection should be performed under aseptic conditions.

Rebospan contains two types of betamethasone esters, one of which (betamethasone sodium phosphate) is rapidly absorbed at the injection site.

Dose reduction should be considered under close medical supervision. In addition, it is sometimes necessary to observe the patient’s condition for up to 1 year after the end of long-term treatment or after high doses administration.

In case of prolonged corticosteroid therapy it is necessary to consider switching from parenteral to oral drug administration estimating all benefits and possible risks.

Corticosteroids should be injected deep into the muscles to avoid local tissue atrophy.

The injection of corticosteroids into soft tissue or directly into the lesion as well as intra-articular administration can have systemic and local effect.

Excipients

Rebospan contains benzyl alcohol which can cause toxic and anaphylactoid reactions in newborns and children under 3 years old. The drug is not to be used in premature or mature infants.

Rebospan contains methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) in its composition that can cause allergic reactions (sometimes delayed type) and in exceptional cases – difficulty in breathing.

ADMINISTRATION IN PREGNANCY AND LACTATION:

Due to the lack of glucocorticoids safety studies in pregnant and lactating women, they should not be prescribed in women during pregnancy, lactation and women at childbearing age unless it is necessary and only after careful assessment of the expected benefit and possible risk ratio for mother,

EFFECT ON ABILITY TO DRIVE AND USE MACHINES:

Particular caution should be exercised when taking high doses of the drug which can affect the central nervous system (euphoria, insomnia). Visual impairment is also possible with prolonged treatment.

fetus or baby.

If corticosteroid therapy is indicated in the prenatal period, the expected clinical effect and possible side effects (in particular, growth retardation and increased risk of infection) should be considered.

In some cases it is necessary to continue corticosteroid therapy during pregnancy or even increase the dose (for example in case of corticosteroid replacement therapy).

Corticosteroids easily penetrate through the placental barrier and into mother's milk. Since corticosteroids cross the placenta, the condition of newborns and infants born to mothers treated with corticosteroids during most or any part of pregnancy period should be monitored especially carefully and examined for possible congenital cataracts, although such cases are very rare.

Since Rebospan can cause side effects in breast-fed infants it is necessary to make consideration regarding advisability to stop or continue breastfeeding and using the drug, depending on importance of this therapy to woman-mother.

Women treated with corticosteroids in pregnancy should be monitored through and after contractions as well as during childbirth to detect adrenal cortex insufficiency caused by birth stress.

PEDIATRIC USE:

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

Rebospan contains benzyl alcohol, which can cause toxic and anaphylactoid reactions in newborns and children under 3. It is prohibited to use the drug in premature or full-term infants.

INTERECTIONS WITH OTHER DRUGS:

Concomitant use of phenobarbital, rifampicin, phenytoin or ephedrine can enhance corticosteroids metabolism and as a result reduce the therapeutic effect.

The following types of treatment are contraindicated in patients receiving corticosteroid therapy:

• smallpox vaccination,

• other methods of immunization (especially at high doses) caused by the danger of neurological complications and a weak immune response (insufficient response of antibodies).

However, in patients using corticosteroids as a replacement therapy immunization can be carried out (for example, in case of Addison’s disease).

It is necessary to monitor the patients’ condition in case of concomitant treatment with corticosteroids and estrogens since the corticosteroids effect may be enhanced. Simultaneous use of corticosteroids with cardiac glycosides may increase the risk of arrhythmias or digital intoxication due to hypokalemia.

In case of concomitant use with non-steroidal anti-inflammatory drugs or ethanol an increased risk of developing a gastrointestinal ulcer or exacerbation of an existing ulcer is possible.

In some cases patients with diabetes mellitus may need to adjust the dose of oral antidiabetic drugs or insulin taking into account the hyperglycemic effect of glucocorticosteroids.

Administration of local anesthetics may rarely be necessary. In case of simultaneous administration of anesthetic desired Rebospan can be mixed (in a syringe, not in a vial) with 1% or 2% solution of lidocaine or procaine hydrochloride or other paraben-free anesthetics. The use of anesthetics containing methylparaben, propylparaben, phenol and other similar substances is not permitted.

STORAGE CONDITIONS:

Keep in a place protected from sunlight at temperature not more than 25°С.

Keep out of reach of children! Protect from freezing!

Shake before use.

 SHELF LIFE:

Shelf life is 2 year from the production date. Do not use after shelf life expiration.

PRESCRIPTION STATUS

By prescription

* For more information, read the instruction for the drug use.

Packaging

1ml of the drug in a clear glass ampule grade I.

5 ampules in a blister pack.

1 blister pack with a leaflet in a carton pack.

Manufacturer Information

Foreign production and trade unitary enterprise “Reb-Pharma”, 223216, Republic of Belarus, Minsk region, Chervensky district, Smilovichi, Sadovaya st., 1, tel./fax: (+375) 17 240 26 35,

e-mail: rebpharma@rebpharma.by, http://www.rebpharma.by