Glucocorticosteroids (GCS), penetrating through cell membranes, form complexes with specific cytoplasmic receptors. The resulting complexes penetrate to the cell nucleus, where they bind to DNA (chromatin). Subsequently, these complexes stimulate mRNA transcription with subsequent synthesis of various enzymes, which explains the effect of GCS when used systemically. GCS not only have a significant effect on the inflammatory process and immune response, but also affect carbohydrate, protein and fat metabolism.
The maximum pharmacological activity of GCS occurs not at the peak of concentration – in plasma – but afterwards. This way the main reason of GCS action is their influence on enzyme activity.
It has anti-inflammatory, anti-shock, desensitizing, anti-toxic, anti-allergic, immunosuppressive and antimetabolic effects. Unlike cytostatics, immunosuppressive properties are not associated with mitostatic action, but are the sum result of the suppression of different stages of immunogenesis: stem cell migration (bone marrow), B-cell migration and the interaction of T and B-lymphocytes.
Inhibits the release of cytokines (interleukins and interferon) from lymphocytes and macrophages, inhibits the release of inflammatory mediators by eosinophils, reduces the metabolism of arachidonic acid and the synthesis of prostaglandins. By stimulating steroid receptors, it induces the formation of lipocortin. It promotes deposition of glycogen in the liver, increases blood glucose levels, inhibits excretion of sodium and water ions, increases excretion of potassium ions from the body, reduces histamine synthesis.
Moves inflammatory cellular infiltrates, reduces migration of leukocytes and lymphocytes into the inflamed area. In high doses inhibits the development of lymphoid and connective tissue, including reticuloendothelial system (REC), reduces the number of mast cells, which are the site of formation of hyaluronic acid; inhibits hyaluronidase and helps to reduce capillary permeability. Inhibits the synthesis and accelerates the breakdown of proteins. Affects the pituitary gland and inhibits corticotropin production. Prolonged administration can lead to suppression and atrophy of the adrenal cortex, inhibition of the formation of gonadotropic and thyroid hormones of the pituitary gland.
Itching, Dermatitis, Joint pain (arthralgia), Rheumatoid arthritis, Eczema, Psoriasis, Allergies, Insect bites
- Primary or secondary adrenal insufficiency (the drugs of choice are hydrocortisone or cortisone; if necessary, their synthetic analogs can be used in combination with mineralocorticoids, especially in pediatric practice);
- acute adrenal insufficiency (hydrocortisone or cortisone are the drugs of choice; simultaneous use of mineralocorticoids may be necessary).
As symptomatic therapy:
- in the preoperative period, in cases of severe trauma or severe illness, in patients with established or suspected adrenal insufficiency;
- Shock that is not amenable to conventional therapy when adrenal insufficiency may be present;
- congenital adrenal hyperplasia;
- subacute thyroiditis;
- hypercalcemia against a background of cancer.
Rheumatic diseases (as adjunctive therapy for a short-term recovery from an acute condition or exacerbation):
- acute and subacute bursitis;
- acute gouty arthritis;
- acute nonspecific tenosynovitis;
- ankylosing spondylitis;
- posttraumatic osteoarthritis;
- psoriatic arthritis;
- rheumatoid arthritis, including juvenile rheumatoid arthritis (low-dose maintenance therapy may be required in some cases);
- synovitis in osteoarthritis.
Systemic connective tissue diseases (during exacerbation or in selected cases as maintenance therapy):
- acute rheumatic carditis;
- systemic dermatomyositis (polymyositis);
- systemic lupus erythematosus.
- herpetiform bullous dermatitis;
- exfoliative dermatitis;
- fungal mycosis;
- painful erythema exudative (Stevens-Johnson syndrome);
- severe psoriasis;
- severe seborrheic dermatitis.
Allergic conditions (in the case of severe or disabling conditions in which conventional therapy is ineffective):
- acute noninfectious laryngeal edema;
- atopic dermatitis;
- asthmatic status;
- contact dermatitis;
- drug hypersensitivity reactions;
- seasonal or year-round allergic rhinitis;
- serum disease;
- posttransfusion reactions such as urticaria.
Eye diseases (severe acute and chronic allergic and inflammatory processes with eye damage):
- allergic conjunctivitis;
- allergic marginal corneal ulcers;
- inflammation of the anterior segment;
- diffuse posterior uveitis and chorioiditis;
- the ocular form of Herpes zoster;
- irritis and iridocyclitis;
- optic nerve neuritis;
- sympathetic ophthalmia.
Diseases of the gastrointestinal tract (to bring the patient out of critical condition):
- ulcerative colitis (systemic therapy);
- regional enteritis (systemic therapy).
Diseases of the respiratory tract:
- aspiration pneumonitis;
- multiple and disseminated pulmonary tuberculosis in combination with appropriate antituberculosis chemotherapy;
- Leffler’s syndrome unresponsive to therapy by other means;
- clinically pronounced sarcoidosis.
- acquired (autoimmune) hemolytic anemia;
- congenital (erythroid) hypoplastic anemia;
- erythroblastopenia (erythrocytic anemia);
- idiopathic thrombocytopenic purpura in adults (IV administration only; IV administration contraindicated);
- secondary thrombocytopenia in adults.
Cancer diseases (as palliative therapy):
- acute leukemia in children;
- leukemia and lymphoma in adults.
- to stimulate diuresis and achieve remission of proteinuria in patients with nephrotic syndrome without uremia; in idiopathic nephrotic syndrome or in lupus erythematosus.
- shock developed due to adrenal insufficiency, or resistant to standard therapy, in the possible presence of adrenal insufficiency;
- acute allergic manifestations after administration of epinephrine (asthmatic status, anaphylactic reactions, insect bites, etc.
- in therapy of hemorrhagic traumatic and surgical shocks in which the standard therapy is ineffective.
Other indications for use:
- trichinellosis with nervous system or myocardial involvement;
- tuberculous meningitis with subarachnoid block or at risk of block (in combination with appropriate anti-TB chemotherapy).
1 bottle contains hydrocortisone (in the form of sodium succinate) 100 mg;
How to take, the dosage
The drug may be administered as an IV or IM injection or as an IV infusion, but in acute conditions, it is preferable to start treatment with an IV injection. At the end of the acute period, either parenteral dosage forms of the drug with longer duration of action or oral forms of the drug are prescribed. Treatment with the drug begins with an IV for 30 s (e.g., 100 mg) and up to 10 minutes (e.g., 500 mg or more). High doses of GCS should be administered only until the patient’s condition has stabilized, but for no longer than 48-72 hours. The initial dose of the drug is 100-500 mg or more, depending on the severity of the patient’s condition. The dose is administered repeatedly every 2, 4 or 6 hours depending on the response of the patient’s body and the clinical picture of the disease. Lower doses (but not less than 25 mg/day) should be given in children, but when choosing the dose, the severity of the condition and the patient’s response to therapy should be primarily considered, rather than age and body weight.
Preparation of solutions
Parenteral preparations should be checked visually for color changes or particulates. Only a clear solution should be used.
For intravenous or intravenous injection, prepare the solution by adding to the vial (observing the rules of antisepsis) not more than 2 ml of water for injection or aqueous sodium chloride solution for injection with a bacteriostatic additive. For IV infusion, the solution is first prepared by adding not more than 2 ml of water for injection to the vial, then this solution can be added to 100-1000 ml of 5% aqueous dextrose solution (or 0.9% sodium chloride solution, or 5% dextrose solution in 0.9% sodium chloride solution if the patient does not need sodium restriction).
The ACT-O-VIAL Dual Cap Vial
1. Press the plastic activator to allow the solvent to pour into the lower container.
2. gently rock the vial until the lyophilizate dissolves.
3. Remove the plastic disc that covers the center of the cap.
4. cauterize the surface of the tube with an antiseptic.
5. Prick the center of the tube with a needle so that the tip of the needle is visible. Invert the vial and draw out the desired amount of solution with the syringe.
For intravenous or intramural injections no further dilution is necessary. For intravenous infusion, the solution is first prepared as described above, then the resulting solution is added to 100-1000 ml of 5% aqueous dextrose solution (or 0.9% sodium chloride solution, or 5% dextrose solution in 0.9% sodium chloride solution if the patient does not need sodium restriction). If a small volume of fluid is desired, you can add 100-3000 mg of hydrocortisone (as hydrocortisone sodium succinate) to 50 ml of the above solutions. The resulting solutions are stable for 4 h and can be administered by IV directly or via a second IV.
If the drug solutions are prepared as above, pH = 7-8 and osmolarity = 0.36 osmol (osmolarity of 0.9% sodium chloride solution 0.28 osmol).
Hepatic microsomal enzyme inducers such as phenobarbital, phenytoin, and rifampicin may increase clearance of GCS, which may require increasing the dose of the drug to obtain the desired effect.
Drugs such as troleandomycin and ketoconazole can inhibit the metabolism of GCS and decrease its clearance. If this occurs, the dose of GKS should be reduced to avoid overdose events.
The GCS can increase clearance of acetylsalicylic acid taken in high doses for a long period, which can lead to decreased serum concentrations of salicylates or increase the risk of toxicity of salicylates during withdrawal of GCS. In patients with hypoprothrombinemia, acetylsalicylic acid in combination with GCS should be prescribed with caution.
The effect of GCS on the effect of indirect anticoagulants is variable. Both enhancement and reduction of the effect of anticoagulants taken concomitantly with hydrocortisone have been reported. Continuous determination of blood clotting parameters is necessary to maintain the desired effect of anticoagulant.
Hypernatremia may occur if high doses of hydrocortisone are administered for a period longer than 48-72 hours. In this case, it is recommended to replace Solu-Cortef with another GKS, such as methylprednisolone sodium succinate, which causes little or no retention of sodium in the body.
Patients who may be stressed by GCS therapy are indicated to increase the dose of the drug before, during and after the stressful situation. These patients should be closely monitored by a physician because of the possibility of adrenal insufficiency.
With GCS therapy, some infections may occur in a milder form, and new infections may also develop. With GCS use, resistance to infections may decrease and the ability of the body to localize the infectious process may decrease. The development of infections caused by various pathogenic organisms such as viruses, bacteria, fungi, protozoa or helminths that localize in different systems of the human body can be associated with the use of GCS, either as monotherapy or in combination with other immunosuppressants affecting cellular immunity, humoral immunity or neutrophil function. These infections may be mild, but in some cases a severe course and even death are possible. The higher doses of GCS are used, the greater the likelihood of infectious complications.
The use of hydrocortisone in active tuberculosis should be limited to cases of fulminant and disseminated tuberculosis, when GCS is used to treat the disease in combination with appropriate anti-tuberculosis chemotherapy. If GKS are administered to patients with latent tuberculosis or with positive tuberculin tests, the treatment should be performed under close medical supervision, since reactivation of the disease is possible. During long-term therapy with the drug, such patients should receive appropriate prophylactic treatment.
Patients treated with GCS at doses that are immunosuppressive are contraindicated in live or live-weakened vaccines, but killed or inactivated vaccines may be given, but the response to administration of these vaccines may be reduced. Patients treated with GCS in doses that are not immunosuppressive may be immunized for appropriate indications.
Hydrocortisone administration may lead to increased blood pressure, water and salt retention in the body, and increased potassium excretion. Restriction of salt intake with food and additional potassium supplementation may be necessary. All GCSs increase calcium excretion from the body. Since patients receiving parenteral GCS therapy may in rare cases have anaphylactoid reactions (e.g., bronchospasm), appropriate preventive measures should be taken before the drug administration, especially if this patient has a history of allergic reactions to any medications.
Long daily therapy with GCS in children may lead to growth retardation, so this dosing regimen should be used in children only if there is a strong indication. Acute myopathy most commonly develops with high doses of GCS in patients with impaired neuromuscular transmission (e.g., myasthenia gravis), or in patients simultaneously treated with peripheral myorelaxants (e.g., pancuronium). Such acute myopathy is generalized, can affect the muscles of the eye and respiratory system, lead to the development of traparesis. Creatine phosphokinase may increase. At the same time, improvement or recovery after withdrawal of GCS may occur only after many weeks or even after several years.
Impact on driving and operating machinery
Because of the possibility of side effects on the nervous system (e.g., seizures) and the visual system, persons taking Solu-Cortef should be careful when driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.
After intravenous injection, the Cmax of hydrocortisone in plasma is reached after approximately 30-60 minutes.
Approximately 40-90% of hydrocortisone is bound to plasma proteins. Most of the hydrocortisone binds to one of the globulins (transcortin) and only a small amount binds to albumin. The free unbound fraction of the hormone determines its biological activity, and the bound fraction serves as a reserve.
The metabolism of hydrocortisone occurs mainly in the liver. Within 24 hours, 22-30% of the injected hydrocortisone is excreted in the urine. The drug is almost completely eliminated from the body within 12 hours, so in order to maintain high concentrations of hydrocortisone in the blood it is necessary to administer it in m/m or intravenously every 4-6 hours.
The drug is not indicated in patients with acute and subacute myocardial infarction because its use in these patients may cause spreading of necrosis, delay formation of scar tissue and, therefore, rupture of the heart muscle;
The product, which is available in ACT-O-VIAL dual-volume bottles, is not recommended for use in infants because the solvent contains benzyl alcohol.
The product should be used with caution in the following cases:
- in eye lesions caused by herpes simplex virus, as this may lead to corneal perforation;
- in ulcerative colitis if there is a risk of perforation, abscess or other purulent infection, as well as in diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal failure, arterial hypertension, osteoporosis, myasthenia gravis.
Note: The side effects listed below are typical for all GCS when administered parenterally, not just this medication.
Water-electrolyte balance: sodium retention; chronic heart failure in predisposed patients; arterial hypertension; fluid retention; potassium loss; hypokalemic alkalosis; increased calcium excretion.
Musculoskeletal system disorders: “steroidal” myopathy; muscle weakness; osteoporosis; pathological fractures; vertebral compression fractures; aseptic necrosis of epiphyses of tubular bones; tendon ruptures, especially of Achilles tendon.
In the digestive system: peptic ulcer with possible rupture and bleeding (prophylactic antacid therapy may be indicated); gastric bleeding; pancreatitis; esophagitis; perforation of the intestine; increased serum ALT, ACT and alkaline phosphatase activity (usually these changes are mild, not associated with any clinical syndrome and are reversible after stopping treatment).
Skin disorders: slow healing of wounds; petechiae and ecchymoses; thinning and decreased skin strength; Kaposi’s sarcoma. Kaposi’s sarcoma has been reported in patients treated with GCS. Clinical remission may occur if GCSs are discontinued.
Metabolic side: negative nitrogen balance caused by protein catabolism.
Nervous system disorders: increased intracranial pressure with optic disc edema; pseudotumor of the brain; seizures; mental disorders, including euphoria, insomnia, mood swings, personality changes, depression; acute psychotic manifestations; exacerbation of pre-existing emotional instability or propensity to have psychotic reactions.
Endocrine system disorders: menstrual cycle disorders; development of Icenko-Cushing’s syndrome; suppression of pituitary-adrenal system function; decreased glucose tolerance; manifestation of latent diabetes; increased need for insulin or oral hypoglycemic agents in diabetic patients, growth retardation in children.
Senses: posterior subcapsular cataracts; increased intraocular pressure; exophthalmus.
Immune system disorders: A sterile clinical picture in infectious diseases; activation of latent infections, including reactivation of tuberculosis; occurrence of infections caused by opportunistic pathogens, of any localization, occurring both in mild form and with the possibility of death; hypersensitivity reactions, including anaphylaxis and anaphylactic reactions (eg, bronchospasm, laryngeal edema, urticaria); suppression of reactions in skin tests.
Others: The solvent contains benzyl alcohol, which can cause “Gasping Syndrome” (disorders of the respiratory system manifested by choking) with fatal outcome in premature infants.
Clinical syndrome of acute drug overdose has not been described. Hydrocortisone is excreted by dialysis.
Locoid, Laticort, Hydrocortisone, Hydrocortisone-Pos, Cortef, Locoid Lipokrem, Hydrocortisone ointment
|Conditions of storage|
Store at 15°C to 25°C out of the reach of children. Store the prepared solution at room temperature for not more than 72 hours in a light-protected place.
Pfizer, Puerto Rico
solution for injections and infusions
Buy Solu-Cortef lyophilizate, 100 mg vials+2 ml with delivery to USA, UK, Europe and over 120 other countries.