Diprospan®

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

Composition:

Active substance: betamethasone;

1 ml of suspension contains 6.43 mg of betamethasone dipropionate (equivalent to 5 mg of betamethasone) and 2.63 mg of betamethasone sodium phosphate (equivalent to 2 mg of betamethasone);

Excipients:

for ampoules:

sodium hydrogen phosphate dihydrate; sodium chloride; disodium edetate; polysorbate 80; benzyl alcohol; methylparahydroxybenzoate (E 218); propylparahydroxybenzoate (E 216); sodium carboxymethylcellulose; macrogols; hydrochloric acid; water for injections;

for pre-filled syringes:

anhydrous sodium hydrogen phosphate; sodium chloride; disodium edetate; polysorbate 80; benzyl alcohol; methylparahydroxybenzoate (E 218); propylparahydroxybenzoate (E 216); sodium carboxymethylcellulose; macrogols; hydrochloric acid; water for injections.

Pharmaceutical form. Injection suspension.

Main physicochemical properties: clear, colorless, slightly viscous liquid containing white or almost white dispersible particles, free from foreign particulate matter.

Pharmacotherapeutic group.

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

Pharmacological properties.

Pharmacodynamics.

Betamethasone is a synthetic glucocorticoid agent (9 alpha-fluoro-16-beta-methylprednisolone). Betamethasone exerts a potent anti-inflammatory, antiallergic, and immunosuppressive effect.

Betamethasone does not produce clinically significant mineralocorticoid activity. Glucocorticosteroids diffuse through cell membranes and form complexes with specific cytoplasmic receptors. These complexes then penetrate into the cell nucleus, bind to DNA (chromatin), and stimulate transcription of messenger RNA and subsequent synthesis of proteins of various enzymes. These enzymes will ultimately be responsible for the effects observed with systemic administration of glucocorticoids. In addition to their significant effects on inflammatory and immune processes, glucocorticoids also influence carbohydrate, protein, and lipid metabolism. They also affect the cardiovascular system, skeletal muscles, and the central nervous system.

Effects on inflammatory and immune processes

It is precisely the anti-inflammatory, immunosuppressive, and antiallergic properties of glucocorticoids that form the basis of their use in therapeutic practice. The main aspects of these properties include: reduction in the number of immune-active cells at the site of inflammation, reduction in vasodilation, stabilization of lysosomal membranes, inhibition of phagocytosis, and decreased production of prostaglandins and related compounds.

The anti-inflammatory effect is approximately 25 times greater than that of hydrocortisone and 8–10 times greater than that of prednisolone (on a weight basis).

Effects on carbohydrate and protein metabolism

Glucocorticoids stimulate protein catabolism. In the liver, the released amino acids are converted into glucose and glycogen through the process of gluconeogenesis. Glucose absorption in peripheral tissues is reduced, leading to hyperglycemia and glucosuria, particularly in patients predisposed to diabetes.

Effects on lipid metabolism

Glucocorticoids exert a lipolytic effect. This lipolysis is more pronounced in the extremities. Additionally, the lipolytic effect manifests particularly in the trunk, neck, and head. This combination of effects results in redistribution of fat deposits.

The maximum pharmacological effect of corticosteroids occurs later than peak serum concentrations, indicating that the efficacy of these drugs is primarily due to modification of enzyme activity rather than direct pharmacological action.

Pharmacokinetics.

Betamethasone sodium phosphate and betamethasone dipropionate are absorbed from the site of administration and produce both local and systemic therapeutic and other pharmacological effects.

Betamethasone sodium phosphate is well water-soluble and is metabolized in the body to form betamethasone—the biologically active steroid. 2.63 mg of betamethasone sodium phosphate is equivalent to 2 mg of betamethasone.

The presence of betamethasone dipropionate provides prolonged activity of the drug. This component is practically insoluble and forms a depot at the injection site, thus being slowly absorbed and ensuring symptom relief over a longer period.

Metabolism of betamethasone occurs in the liver. Betamethasone is primarily bound to albumin. In patients with impaired liver function, clearance of betamethasone is slower or delayed.

Clinical characteristics.

Indications.

Corticosteroid therapy is an adjunctive, not an alternative to conventional treatment.

Dermatological diseases

Atopic dermatitis (nummular eczema), neurodermitis, contact dermatitis, severe solar dermatitis, urticaria, lichen planus, insulin lipodystrophy, alopecia areata, discoid lupus erythematosus, psoriasis, keloid scars, pemphigus vulgaris, herpes 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 callus, 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 lymphomas 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 concomitant administration of mineralocorticoids required).

Contraindications.

• Hypersensitivity to the active substances or to any of the excipients listed in the section "Composition".
• Hypersensitivity to corticosteroids.
• Systemic fungal infections.
• Intramuscular administration in patients with idiopathic thrombocytopenic purpura.

Interaction with other medicinal products and other forms of interactions.

Interaction with other medicinal products

Concomitant administration of phenobarbital, rifampicin, phenytoin, or ephedrine may enhance the metabolism of corticosteroids, thereby reducing their therapeutic activity.

Patients receiving corticosteroid therapy must not receive the following treatments:

• Smallpox vaccination;
• Other immunization procedures (especially when high doses are used) due to the risk of neurological complications and inadequate antibody response.

However, immunization may be performed in patients receiving corticosteroids as replacement therapy (e.g., in Addison's disease).

Combination with diuretics such as thiazides may increase the risk of glucose intolerance.

Patients receiving corticosteroids and estrogens concurrently should be monitored for possible excessive corticosteroid effects.

Concomitant use of corticosteroids and cardiac glycosides may increase the risk of arrhythmias or signs of digitalis toxicity associated with hypokalemia. Patients taking cardiac glycosides often also receive diuretics promoting potassium loss; in such cases, potassium levels should be closely monitored. Corticosteroids may potentiate potassium loss induced by amphotericin B. In all patients receiving any of these drug combinations, serum electrolyte levels, especially serum potassium, should be carefully monitored.

Concomitant use of corticosteroids and coumarin-type anticoagulants may lead to increased or decreased anticoagulant effect, possibly requiring dose adjustment. In patients receiving anticoagulants in combination with glucocorticoids, the potential for corticosteroid-induced gastrointestinal ulceration or increased risk of internal bleeding should be considered.

Corticosteroids may reduce plasma salicylate concentrations when used concomitantly. Acetylsalicylic acid should be used cautiously in combination with corticosteroids in patients with hypoprothrombinemia. When corticosteroid dosage is reduced or treatment discontinued, patients should be monitored for possible salicylate poisoning. Combination of corticosteroids with salicylates may increase the frequency and severity of gastrointestinal ulcers.

Combined use of glucocorticosteroids with nonsteroidal anti-inflammatory drugs or alcohol may increase the risk of gastrointestinal ulceration or worsen the condition of an existing ulcer.

For diabetic patients, dosage adjustment of oral antidiabetic agents or insulin may sometimes be necessary due to the hyperglycemic effect of corticosteroids.

Concomitant administration of glucocorticosteroids and somatotropin may slow the 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.

Combined therapy with CYP3A inhibitors, including products 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.

Other forms of interactions

Effect on laboratory tests

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

Corticosteroid therapy should also be taken into account when interpreting biological parameters and test results in patients (skin tests, thyroid hormone levels, etc.).

Special precautions for use.

DiprospanÒ suspension is not intended for intravenous or subcutaneous administration.

Serious neurological events, including fatalities, have been reported following epidural injection of corticosteroids. These include spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. Such serious neurological complications have occurred both with and without the use of fluoroscopy. As the safety and efficacy of epidural administration have not been established, corticosteroids are not recommended for epidural use.

Rarely, anaphylactoid/anaphylactic reactions with potential for shock have been observed in patients receiving parenteral corticosteroid therapy. Appropriate precautionary measures should be taken in patients with a history of allergic reactions to corticosteroids.

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

Strict adherence to aseptic techniques is mandatory when using this medication.

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

Abrupt discontinuation or dose reduction after prolonged use (especially with high doses over a short period) or increased demand for corticosteroids (due to stress: infection, trauma, surgery) may lead to adrenal insufficiency. In such cases, the dose should be tapered gradually. During periods of stress, corticosteroid therapy may need to be reinstituted or the dose increased.

Dose reduction must be performed under strict medical supervision; monitoring of the patient may be required for up to one year after discontinuation of prolonged or high-dose therapy.

Symptoms of adrenal insufficiency include malaise, muscle weakness, mental disturbances, lethargy, muscle and joint pain, skin desquamation, dyspnea, anorexia, nausea, vomiting, fever, hypoglycemia, hypotension, dehydration, and even death following abrupt withdrawal. Treatment of adrenal insufficiency includes administration of corticosteroids, mineralocorticoids, water, sodium chloride, and glucose.

Rapid intravenous administration of high-dose corticosteroids may lead to cardiovascular collapse; therefore, the injection should be administered over a 10-minute period.

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

When performing intra-articular injections, it is important to know that:

• such injections may produce both local and systemic effects;
• joint fluid should always be examined to exclude the possibility of septic processes;
• local injection should not be administered into previously infected joints;
• marked increase in pain and local swelling, further limitation of joint mobility, fever, and malaise may indicate septic arthritis. If this diagnosis is confirmed, appropriate antibacterial therapy should be initiated;
• corticosteroids must not be injected into unstable joints, infected areas, or the intervertebral space;
• repeated intra-articular injections in osteoarthritic joints may accelerate joint destruction;
• after successful intra-articular therapy, patients should avoid overloading the joint;
• corticosteroids must not be injected directly into tendons, as this may lead to tendon rupture.

Intramuscular injections of corticosteroids should be administered deeply into muscle tissue to prevent local tissue atrophy.

Injection of corticosteroids into soft tissues, lesion sites, or joints may result in both systemic and local effects.

Special patient groups at risk

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

Enhanced corticosteroid effects have been observed in patients with hypothyroidism or hepatic cirrhosis.

DiprospanÒ should be avoided in patients with herpetic eye infections (due to the risk of corneal perforation).

Psychiatric disturbances may occur during corticosteroid therapy. Treatment with corticosteroids may increase susceptibility to emotional instability or psychosis.

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

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

Corticosteroid therapy may mask signs of infection or complicate its diagnosis. Due to decreased resistance, new infections may arise during such therapy.

Prolonged treatment may lead to the development of posterior subcapsular cataracts (especially in children) or glaucoma, which may cause optic nerve damage and increase the risk of secondary fungal or viral ocular infections. Regular ophthalmological examinations are necessary during prolonged therapy (more than 6 weeks).

Moderate to high doses of corticosteroids may cause elevated blood pressure, fluid and sodium retention, and increased potassium excretion. These effects are less likely with synthetic derivatives unless used at high doses. A low-sodium diet and potassium supplementation may be considered. All corticosteroids accelerate calcium excretion.

Patients receiving corticosteroid therapy should not undergo:

• smallpox vaccination;
• other immunization procedures (especially with high-dose corticosteroids), due to the risk of neurological complications and inadequate antibody response.

However, immunization may be performed in patients receiving corticosteroids as replacement therapy (e.g., in Addison's disease).

Patients, particularly children, receiving immunosuppressive doses of corticosteroids should avoid contact with individuals infected with varicella or measles.

The use of corticosteroids in active tuberculosis is possible only in rapidly progressive or disseminated forms, and only in combination with adequate antituberculosis therapy. Patients with latent tuberculosis or positive tuberculin reaction require close monitoring, as reactivation may occur. Chemoprophylaxis should be administered during prolonged corticosteroid therapy. When rifampicin is used in chemoprophylaxis regimens, increased hepatic metabolism of corticosteroids should be monitored, and dose adjustments may be necessary.

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

Changes in sperm motility and count may occur in some patients receiving glucocorticoids.

DiprospanÒ contains benzyl alcohol.

Benzyl alcohol may cause allergic reactions. It has been associated with serious adverse reactions, including respiratory problems ("gasping syndrome") in children. The minimum amount of benzyl alcohol causing toxicity is unknown. This product should not be used in premature infants or full-term newborns (under 4 weeks of age). It should not be administered for more than one week in young children (under 3 years of age). Large amounts of benzyl alcohol may cause metabolic acidosis. Special safety precautions should be observed when prescribing DiprospanÒ to newborns, pregnant or breastfeeding women, and patients with liver or kidney disease.

DiprospanÒ contains sodium.

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

DiprospanÒ contains methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216), which may cause allergic reactions (possibly delayed), and in rare cases, respiratory difficulty.

Visual disturbances

Visual disturbances may occur with systemic and local (including intranasal, inhaled, and intraocular) corticosteroid use. If symptoms such as blurred vision or other visual disturbances occur, patients should undergo 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.

Use during pregnancy or breastfeeding.

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

Pregnancy

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

In some cases, corticosteroid therapy may need to be continued or even increased during pregnancy (e.g., in replacement therapy).

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

Published data indicate that the 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 against potential risks for both mother and fetus.

Corticosteroids are not indicated 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, eclampsia, or placental disorders.

Infants whose mothers received significant doses of corticosteroids during pregnancy should be closely monitored for signs of adrenal insufficiency.

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 has been observed in newborns whose mothers received betamethasone before delivery. However, suppression of fetal cortisol production did not affect pituitary-adrenal responses to stress after birth.

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

Women who received corticosteroids during pregnancy should be monitored during labor and after delivery to detect adrenal insufficiency caused by delivery-related stress.

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

Breastfeeding

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

Since DiprospanÒ may cause adverse effects in breastfed infants, a decision should be made whether to discontinue breastfeeding or discontinue therapy, taking into account the importance of the therapy for the mother.

Ability to affect reaction speed when driving or operating machinery.

Caution is advised due to central nervous system effects (e.g., euphoria, insomnia) associated with high-dose administration and visual disturbances that may occur during prolonged therapy (see "Adverse reactions" section for details).

Method of Administration and Dosage

Shake before use.

The dosage regimen is established individually, depending on the indications, severity of the disease, and the patient's clinical response to treatment.

Dosage

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

The initial dose should be selected 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 by gradually reducing the dose, and alternative appropriate therapy should be initiated.

In case of a favorable response, the appropriate maintenance dose should be determined by gradually tapering the initial dose at acceptable intervals until the lowest effective dose producing the desired clinical response is reached.

Method of Administration

Diprospan® suspension is intended for intravenous or subcutaneous administration.

Systemic Administration

For systemic use, treatment is usually initiated with an injection of 1–2 mL of the drug, repeated as necessary. The dosage and frequency of administration depend on the severity of the patient's condition and response to therapy. The drug is administered by deep intramuscular injection into the buttock:

• In severe conditions (systemic lupus erythematosus and status asthmaticus) requiring emergency measures, the initial dose may be 2 mL;
• In various dermatological diseases, 1 mL of the drug administered intramuscularly is generally sufficient; administration may be repeated depending on the response to treatment;
• In respiratory diseases, symptom relief occurs within several hours after intramuscular injection of Diprospan®. In bronchial asthma, hay fever, allergic bronchitis, and allergic rhinitis, significant improvement is 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. Several repeat injections may be required if necessary.

Local Administration

Concomitant use of a local anesthetic agent is required only in isolated cases (the injection is practically painless). If concomitant administration of a local anesthetic is desired, Diprospan® may be mixed (in the syringe, not in the vial) with 1% or 2% lidocaine hydrochloride or procaine hydrochloride solution, or similar local anesthetics, using formulations that do not contain parabens. Anesthetics containing methylparaben, propylparaben, phenol, or other similar substances must not be used. When using an anesthetic in combination with Diprospan®, first draw the required dose of the drug from the vial into the syringe, then add the required amount of local anesthetic into the same syringe, and shake the syringe briefly.

In acute bursitis (subdeltoid, subscapular, olecranon, and prepatellar), injection of 1–2 mL of Diprospan® into the synovial sac relieves pain and fully restores mobility within several hours.

Treatment of chronic bursitis is carried out with lower doses of the drug after suppression of acute symptoms.

In acute tenosynovitis, tendinitis, and peritendinitis, a single injection of Diprospan® may relieve the patient's condition; in chronic cases, repeat administration may be necessary depending on the patient's condition.

In rheumatoid arthritis and osteoarthritis, intra-articular injection of the drug at a dose of 0.5–2 mL may reduce joint pain, tenderness, and stiffness within 2–4 hours after administration. The duration of the therapeutic effect varies significantly and may last 4 weeks or longer. Intra-articular administration of Diprospan® is well tolerated by the joint and periarticular tissues.

Recommended doses for injection: into large joints (e.g., knee, hip) – 1–2 mL; into medium joints (e.g., elbow) – 0.5–1 mL; into small joints (e.g., wrist) – 0.25–0.5 mL.

In dermatological diseases, effective treatment involves intradermal injection of the drug directly into the lesion site. The response of some lesions not treated directly may be due to a minor systemic effect of the drug. Administer 0.2 mL/cm² of Diprospan® into the skin (not subcutaneously) using a tuberculin syringe and a 26 G needle. The total amount of drug administered at the injection site should not exceed 1 mL.

Foot disorders sensitive to corticosteroids. Bursitis under a callus can be treated by two consecutive injections of 0.25 mL each. In conditions such as hallux rigidus (flexion contracture of the big toe), tailor's bunion (inward deviation of the fifth toe), and acute gouty arthritis, relief may occur very quickly. For most foot injections, a tuberculin syringe with a 25 G needle 1.9 cm in length is suitable.

Recommended doses of Diprospan® (with intervals between injections approximately 1 week): for bursitis under a 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 Morton's metatarsalgia – 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.

Children

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

Overdose

Symptoms. Acute overdose of glucocorticoids, including betamethasone, does not create life-threatening situations. Administration of high doses of glucocorticosteroids over several days does not lead to adverse consequences (except in cases of very high doses or in patients with diabetes mellitus, glaucoma, exacerbation of erosive-ulcerative gastrointestinal lesions, or in patients concurrently receiving cardiac glycosides, coumarin-derived anticoagulants, or potassium-depleting diuretics).

Treatment. In case of complications arising from metabolic effects of corticosteroids, adverse consequences of the primary or concomitant diseases, or drug interactions, appropriate treatment should be administered. Adequate fluid intake should be maintained, and electrolyte levels in plasma and urine should be monitored (especially sodium and potassium balance in the body). If an imbalance of these ions is detected, appropriate therapy should be initiated.

Adverse Reactions.

Undesirable effects observed during the use of Diprospan®—as with other corticosteroids—are dose- and duration-dependent.

Among the adverse effects associated with corticosteroids in general, the following should be particularly noted:

Electrolyte and fluid imbalance: sodium retention, increased potassium excretion, hypokalemic alkalosis, fluid retention, congestive heart failure in predisposed patients, hypertension, increased calcium excretion.

Musculoskeletal system disorders: muscle weakness, loss of muscle mass, worsening of myasthenic symptoms in severe pseudoparalytic myasthenia, osteoporosis sometimes associated with severe bone pain and spontaneous fractures (vertebral compression fractures), aseptic necrosis of the femoral or humeral heads, tendon ruptures, steroid myopathy, pathological fractures, joint instability.

Skin disorders: skin atrophy, impaired wound healing, thinning and weakening of the skin, petechiae, bruising, skin reactions such as allergic dermatitis, angioneurotic edema, facial erythema, increased sweating, urticaria.

Gastrointestinal disorders: peptic ulceration with possible perforation and hemorrhage, pancreatitis, abdominal distension, intestinal perforation, esophageal ulceration, nausea, vomiting, hiccups.

Neurological disorders: convulsions, dizziness, headache, migraine, increased intracranial pressure (pseudotumor cerebri).

Psychiatric disorders: euphoria, mood swings, personality changes, severe depression, increased irritability, insomnia, psychotic reactions—particularly in patients with a history of psychiatric disorders, depression.

Ophthalmological disorders: elevated intraocular pressure (pseudotumor cerebri: see Neurological disorders), glaucoma, posterior subcapsular cataract, exophthalmos, blurred vision (see also section "Special precautions for use").

Endocrine disorders: clinical features of Cushing's syndrome, menstrual irregularities, increased requirement for insulin injections or oral antidiabetic agents in diabetic patients, delayed fetal or childhood growth, impaired carbohydrate tolerance, manifestation of latent diabetes mellitus, secondary suppression of the pituitary and adrenal cortex—which is particularly harmful under stress conditions (trauma, surgery, or illness).

Metabolic disorders: negative nitrogen balance due to protein catabolism, lipomatosis, weight gain.

Immune system disorders: corticosteroids may suppress skin test reactions, mask signs of infection, activate latent infections, and reduce resistance to infections—particularly to mycobacteria, tuberculosis, Candida albicans, and viruses.

Other disorders: anaphylactic or allergic reactions, hypotensive reactions or reactions associated with shock.

The following adverse reactions may occur with parenteral administration of corticosteroids:

Cases of blindness associated with intralesional injection in the head area, particularly the face; hyper- or hypopigmentation; subcutaneous and cutaneous atrophy; sterile abscesses; post-injection flare (after intra-articular injection); and Charcot arthropathy.

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

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after the medicinal product has been authorized. This enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to report any suspected adverse reactions.

Shelf life. 2 years.

Storage conditions.

Keep out of reach of children. Store at temperatures not exceeding 25°C, protected from light. Do not freeze. Shake well before use.

Incompatibilities. Rarely, there may be a need for concomitant administration of a local anesthetic. If Diprospan® is to be administered simultaneously with a local anesthetic, it may be mixed (in the syringe, not in the vial) with 1% or 2% lidocaine hydrochloride or procaine hydrochloride solution, provided that the anesthetic does not contain parabens. Similar local anesthetics may also be used. Anesthetics containing methylparaben, propylparaben, phenol, etc., should be avoided.

Packaging.

For ampoules: 1 ml in glass ampoules, 5 ampoules per cardboard box.

For pre-filled syringes: 1 ml of suspension in a single-use syringe made of colorless glass with a 2 ml graduated scale. The syringe is sealed at one end with a removable rubber cap and at the other end with a plastic plunger and a screw cap. Each syringe is supplied in a sterile individual package with 1 or 2 sterile needles, contained in a transparent plastic container sealed with a paper membrane. One container per cardboard box.

Prescription category. Prescription only.

Manufacturer.

For ampoules:

Organon Heist bv, Belgium.

Organon Heist bv, Belgium.

For pre-filled syringes:

CENEXI HSC, France.

CENEXI HSC, France.

Organon Heist bv, Belgium.

Organon Heist bv, Belgium.

Manufacturer's address and place of business.

For ampoules:

Industriepark 30, 2220, Heist-op-den-Berg, Belgium.

Industriepark 30, 2220, Heist-op-den-Berg, Belgium.

For pre-filled syringes:

2 rue Louis Pasteur, Herouville Saint Clair, 14200, France.

2 rue Louis Pasteur, Herouville Saint Clair, 14200, France.

Industriepark 30, 2220, Heist-op-den-Berg, Belgium.

Industriepark 30, 2220, Heist-op-den-Berg, Belgium.