Pharmacological properties
The therapeutic activity of the drug SOLU-CORTEF is identical to the activity of hydrocortisone. GCS, penetrating through cell membranes, form complexes with specific cytoplasmic receptors. The formed complexes penetrate the cell nucleus, where they bind to DNA (chromatin). These complexes subsequently stimulate mRNA transcription with subsequent synthesis of various enzymes that are directly responsible for the corresponding reaction of the body after the administration of GCS. Since the maximum pharmacological effect of corticosteroids is achieved later in time than the peak concentrations of drugs in the blood, it can be assumed that the therapeutic effect of the drug is mainly due to the modification of enzyme activity.
After intramuscular administration of the drug, its maximum concentration in blood plasma is reached approximately 30-60 minutes later.
40-90% of hydrocortisone binds to plasma proteins. The largest amount of hydrocortisone binds to one of the globulins (transcortin) and only a small amount to albumin.
The free, unbound fraction of the hormone determines its biological activity, and the bound fraction performs a reserve function. Metabolism of hydrocortisone occurs mainly in the liver.
Within 24 hours, 22-30% of the drug administered intramuscularly or intravenously is excreted from the body in the urine.
The administered dose of the drug is almost completely eliminated from the body within 12 hours, therefore, to maintain high concentrations of the drug in the blood, it is necessary to administer it intramuscularly or intravenously every 4-6 hours.
Indication
Endocrine disorders - primary or secondary adrenal cortical insufficiency; acute adrenal cortical insufficiency; in the preoperative period, with severe injuries or severe course of the disease, with adrenal insufficiency or doubts about the reserve capabilities of the adrenal glands; shock that is not amenable to other types of treatment, when adrenal cortical insufficiency is detected or suspected; congenital adrenal hyperplasia; non-purulent thyroiditis; hypercalcemia due to tumor disease.
Rheumatic diseases - as short-term adjunctive therapy in exacerbations or acute stages of the following diseases: post-traumatic osteoarthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis; ankylosing spondylitis; acute and subacute bursitis; acute nonspecific tendosynovitis; acute gouty arthritis; psoriatic arthritis; synovitis in osteoarthritis; epicondylitis.
Systemic connective tissue diseases - prescribed during exacerbations or as maintenance therapy for: systemic lupus erythematosus; acute rheumatic carditis; systemic dermatomyositis (polymyositis).
Skin diseases - pemphigus; bullous dermatitis herpetiformis; polymorphic bullous erythema (Stevens-Johnson syndrome); exfoliative dermatitis; fungal mycosis; severe psoriasis; severe seborrheic dermatitis.
Allergic diseases - the drug is prescribed for severe or severe allergic reactions that are not amenable to other types of treatment. These include: seasonal or perennial allergic rhinitis; serum sickness; asthma; hypersensitivity reactions to drugs; contact dermatitis; atopic dermatitis; transfusion reactions such as urticaria; acute non-infectious laryngeal edema.
Eye diseases - severe acute or chronic allergic and inflammatory processes with eye damage, including: allergic corneal ulcer; ocular form of Herpes zoster; anterior segment inflammation; diffuse posterior uveitis and choroiditis; sympathetic ophthalmia; allergic conjunctivitis; keratitis; chorioretinitis; optic neuritis; iritis, iridocyclitis.
Diseases of the digestive tract - prescribed as systemic treatment in the critical stage of the disease in ulcerative colitis; regional enteritis.
Respiratory diseases - symptomatic sarcoidosis; Loeffler's syndrome, which is not amenable to other types of treatment; berylliosis; fulminant or disseminated form of pulmonary tuberculosis with simultaneous administration of appropriate anti-tuberculosis chemotherapy; aspiration pneumonia.
Blood diseases - idiopathic thrombocytopenic purpura in adults; secondary thrombocytopenia in adults; acquired (autoimmune) hemolytic anemia; erythroblastopenia (erythrocytic anemia); congenital (erythroid) hypoplastic anemia.
Malignant diseases - as palliative therapy for leukemias and lymphomas in adults; acute leukemias in children.
Edema. It is prescribed to increase diuresis or reduce proteinuria in nephrotic syndrome without uremia; in idiopathic nephrotic syndrome or in systemic lupus erythematosus.
Emergency conditions - SOLU-CORTEF is effective in shock due to adrenal insufficiency or shock resistant to standard therapy; in cases where adrenal insufficiency is suspected; and in acute allergic reactions (asthmatic status, anaphylactic reactions, insect bites) after the use of adrenaline.
Other indications are tuberculous meningitis with the development of subarachnoid block or with the threat of its development in combination with appropriate anti-tuberculosis chemotherapy; trichinellosis with damage to the nervous system or myocardium.
The drug can be administered intravenously as a bolus or drip, intramuscularly. If the drug is prescribed as an emergency treatment for acute conditions, it is recommended to use it intravenously. After the acute period, longer-acting dosage forms of the drug or oral forms of the drug are administered parenterally. Treatment with SOLU-CORTEF begins with intravenous administration over 30 seconds (for example, 100 mg) and up to 10 minutes (for example, 500 mg or more). High doses of corticosteroids should be used only until the patient's condition stabilizes, but generally no more than 72 hours. The initial dose of SOLU-CORTEF in adults is 100-150 mg or more, depending on the severity of the patient's condition. In this dose, the drug is repeated every 2-4-6 hours, depending on the patient's response and the clinical picture of the disease. When prescribed to children, the dose of the drug is reduced accordingly, but should not be less than 25 mg per day.
In idiopathic thrombocytopenic purpura in adults, the drug is prescribed only intravenously; intramuscular administration is contraindicated.
If patients find themselves in a stressful situation after GCS therapy, they should be under strict medical supervision due to the possible development of adrenal insufficiency.
GCS therapy is prescribed as an adjunct and does not replace standard treatment.
Preparation of R-POR
Parenteral preparations should be inspected visually for discoloration or particulate matter whenever the solution and packaging permit.
100 mg vial
For IV or IM injection, prepare the solution by adding to the vial (observing the rules of antiseptics) no more than 2 ml of bacteriostatic water for injection or sodium chloride solution for injection with a bacteriostatic additive, gently shaking the vial until the powder is completely dissolved. For IV infusion, first prepare the solution by adding to the vial no more than 2 ml of bacteriostatic water for injection; then this solution can be added to 100 or 1000 ml of 5% glucose solution in water (or saline, or 5% glucose solution in saline, if the patient does not require sodium restriction).
Two-volume bottle ACT-0-Vial
1. Press the plastic activator so that the solvent flows into the lower container.
2. Gently shake the bottle until the powder dissolves.
3. Remove the plastic disc that covers the center of the plug.
4. Treat the surface of the cork with a suitable antiseptic.
5. Pierce the center of the stopper with a needle so that the tip of the needle is visible. Invert the vial and draw the required amount of solution with a syringe.
For IV or IM injections, no further dilution is required. For IV infusion, the solution is first prepared as described above. This solution is then added to 100 or 1000 ml of 5% glucose solution in water (or saline, or 5% glucose solution in saline if the patient does not require sodium restriction). In cases where it is desirable to administer 100 to 3000 mg of hydrocortisone (calculated as hydrocortisone sodium succinate) in a small volume of fluid, up to 50 ml of the above dilution solutions can be added. The resulting solutions are stable for 4 hours and can be administered IV directly or through a separate dropper. If the drug solutions are prepared as described above, the pH will be 7 to 8 and the osmolarity will be 0.36 osmoles (saline = 0.28 osmoles).
Contraindication
Systemic fungal infections; hypersensitivity to the drug.
Side effects
The side effects listed below are typical of all corticosteroids (systemic effects).
Disturbances of water and electrolyte balance: sodium and fluid retention in the body; congestive heart failure in susceptible patients; hypokalemia; hypokalemic alkalosis; hypertension, increased calcium excretion.
Musculoskeletal disorders: aseptic necrosis of the heads of the humerus and femur; steroid myopathy; muscle weakness; osteoporosis; pathological fractures; compression fractures of the spine, rupture of ligaments, especially the Achilles tendon.
Digestive system disorders: development of ulcers with possible perforation and bleeding; nausea; gastric bleeding; pancreatitis; esophagitis; intestinal perforation; increased activity of transaminases (ALT, AST), LF (usually these phenomena are insignificant, not accompanied by pronounced clinical symptoms and quickly disappear after discontinuation of the drug).
Dermatological disorders: impaired wound healing; petechiae and ecchymoses; skin thinning, Kaposi's sarcoma.
Metabolic disorders: negative nitrogen balance due to protein catabolism.
Neurological disorders: increased intracranial pressure; symptom of pseudotumor cerebri; mental disorders (euphoria, insomnia, mood disorders, personality changes, depression, increased emotional lability); seizures.
Endocrine disorders: menstrual cycle disorders; development of Cushingoid syndrome; suppression of the pituitary-adrenal axis; decreased carbohydrate tolerance; manifestation of latent diabetes mellitus; increased need for insulin or oral hypoglycemic drugs used in diabetes mellitus; growth suppression in children.
Immune system: masking of clinical manifestations of infections; activation of latent infections; opportunistic infections; suppression of the response to allergens during skin testing. In addition, some anaphylactic reactions (e.g. bronchospasm, laryngeal edema, urticaria) have been associated with parenteral use of corticosteroids.
Special instructions
Hydrocortisone or cortisone are the drugs of choice; their synthetic analogues can (sometimes need to) be used in combination with mineralocorticoids; the use of mineralocorticoids is particularly indicated in pediatric practice.
Adverse reactions when using high doses of GCS for a short period develop rarely, but peptic ulcers are possible. Prophylactic antacid therapy may be indicated. When using high doses of hydrocortisone for more than 72 hours, hypernatremia may develop. In this case, it is recommended to replace SOLU-CORTEF with another GCS, for example, methylprednisolone sodium succinate, which causes little or no sodium retention in the body.
Patients who use glucocorticosteroids and experience severe stress require increased doses of fast-acting corticosteroids before, during and after a stressful situation. Corticosteroids can mask the symptoms of infection, and new infectious processes can develop during therapy with these drugs. When using corticosteroids, the body's resistance and its ability to localize the infectious process may decrease. The introduction of hydrocortisone in medium and high doses can lead to increased blood pressure, salt and water retention in the body, and increased potassium excretion. When using synthetic derivatives, the risk of developing such phenomena is reduced, provided that they are not used in high doses.
It may be necessary to limit the intake of salt with food and additionally prescribe potassium preparations. All GCS increase the excretion of calcium from the body. During treatment with GCS, vaccination against smallpox cannot be carried out. Due to the possibility of developing neurological complications and the lack of antibody formation in patients receiving GCS therapy (especially high-dose drugs), other types of vaccination should not be carried out. The appointment of the drug SOLU-CORTEF to patients with active tuberculosis should be limited only to those cases of focal or disseminated tuberculosis when appropriate anti-tuberculosis chemotherapy is prescribed in parallel. If the appointment of corticosteroid therapy is indicated for patients with latent tuberculosis or a tuberculin test deviation, careful monitoring of the patient's condition is necessary due to the possibility of disease activation. If prolonged use of GCS is necessary, chemoprophylaxis is performed. Rarely, patients receiving parenteral GCS therapy may experience anaphylactoid reactions, such as bronchospasm, so appropriate precautions should be taken before prescribing the drug, especially in patients with a history of drug allergy. SOLU-CORTEF contains benzyl alcohol, which has sometimes been associated with the development of a fatal gasping syndrome in premature infants.
Studies of methylprednisolone sodium succinate in septic shock suggest that higher mortality rates occur in patients at increased risk (creatinine level above 2.0 mg%; secondary infection), although similar studies have not been conducted with hydrocortisone and other corticosteroids recently. In herpetic eye lesions, SOLU-CORTEF is used with caution due to the risk of corneal perforation.
When using GCS, mental disorders may occur - from euphoria, insomnia, sudden mood swings, personality changes and severe depression to true psychotic manifestations. SOLU-CORTEF may worsen pre-existing emotional instability or psychotic tendencies.
Steroid drugs are used with caution in nonspecific ulcerative colitis, the risk of perforation, the development of an abscess or other purulent infection, as well as in diverticulitis, the presence of fresh intestinal anastomoses, active or latent peptic ulcers, renal failure, arterial hypertension, osteoporosis and myasthenia gravis.
Controlled clinical trials have shown that the use of corticosteroids reduces the duration of exacerbations of multiple sclerosis, but does not affect the course of the disease and its consequences. The studies have shown that relatively high doses of corticosteroids are required to obtain a pronounced therapeutic effect.
Pregnancy and lactation. Animal studies have shown that in some cases, corticosteroids administered to pregnant women in high doses have resulted in impaired fetal development. To date, no appropriate studies have been conducted on the effects of corticosteroids on human reproductive function, therefore, the use of SOLU-CORTEF during pregnancy and lactation requires a careful assessment of the benefit-risk ratio for the mother and fetus. GCS freely cross the placenta. Children born to mothers who received significant doses of SOLU-CORTEF during pregnancy should be carefully monitored for signs of adrenal insufficiency. The effect of GCS on labor is unknown. GCS are excreted in breast milk.
Interactions
In clinical practice, pharmacokinetic interactions should be considered when concomitantly taking drugs that induce liver enzymes (such as phenobarbital, phenytoin, rifampin), as the clearance of corticosteroids may increase and their dose may need to be increased to achieve the desired therapeutic effect. Drugs such as oleandomycin and ketoconazole may inhibit the metabolism of corticosteroids and thus reduce their clearance. In these cases, corticosteroid dose adjustment is also necessary to avoid the development of steroid toxicity. With prolonged use of acetylsalicylic acid in high doses, corticosteroids may accelerate its excretion. This may lead to a decrease in the level of salicylates in the blood serum or to an increase in the risk of salicylate toxicity when stopping the administration of corticosteroids. Acetylsalicylic acid should be prescribed with caution in combination with corticosteroids in patients with hypoprothrombinemia. The effect of corticosteroids on the pharmacokinetics of oral anticoagulants varies. Both increased and decreased efficacy of anticoagulants have been reported when co-administered with corticosteroids. Thus, monitoring of coagulation parameters is necessary to maintain the required anticoagulant effect.
When using immunosuppressive doses of corticosteroids, live or attenuated vaccines are contraindicated.
Overdose
There is no characteristic clinical syndrome in acute overdose of the drug SOLU-CORTEF. Hydrocortisone is excreted by dialysis.
Storage conditions
At a temperature of 15-25 °C, unused solution should be destroyed 3 days after preparation.
