Main physicochemical properties: round white tablets with a dividing line on one side and embossed with the symbol "H" on the other side. The tablet can be divided into equal doses.
Pharmacotherapeutic group
Glucocorticosteroids. ATX code H02A B09.
Pharmacological properties
Pharmacodynamics.
Hydrocortisone belongs to the glucocorticoids. Glucocorticoids belong to the adrenocortical steroids of both natural and synthetic origin, which are easily absorbed from the gastrointestinal tract.
Hydrocortisone is believed to be the principal corticosteroid secreted by the adrenal cortex. Naturally occurring glucocorticosteroids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy for conditions associated with adrenal insufficiency. They are also used because of their potent anti-inflammatory effects in many organ system disorders. Glucocorticoids have a wide range of metabolic effects. They also modify the body's immune response to various stimuli.
Pharmacokinetics.
Absorption
Hydrocortisone is readily absorbed from the gastrointestinal tract, and 90% or more of the active substance is reversibly bound to protein.
Binding is due to two protein fractions: one of them is corticosteroid-binding globulin, and the other is albumin.
Biological transformation
Hydrocortisone is metabolized in the liver and most body tissues to hydrogenated and degraded forms, such as tetrahydrocortisone and tetrahydrocortisol, which are excreted in the urine, conjugated mainly as glucuronides, along with a small amount of unchanged hydrocortisone.
The half-life is approximately 1.5 hours.
Indication
Corticosteroid
For replacement therapy in primary, secondary or acute adrenocortical insufficiency.
Before surgery and in case of serious injury or illness in patients with known adrenocortical insufficiency or questionable adrenal reserve.
Contraindication
Hypersensitivity to the active substance or to any of the excipients included in the medicinal product.
Contraindicated in infections, including systemic infections, when anti-infective therapy has not been initiated.
High doses of corticosteroids slow the immune response to vaccines, so the simultaneous use of live vaccines with corticosteroids should be avoided.
Interaction with other medicinal products and other types of interactions
Drug interactions have been reported with pharmacological doses of corticosteroids, which may not occur with corticosteroid replacement therapy.
Aspirin should be used with caution in combination with corticosteroids in hypoprothrombinemia. There is an increased risk of gastrointestinal bleeding and ulceration when corticosteroids are used with acetylsalicylic acid and nonsteroidal anti-inflammatory drugs (NSAIDs), although topical NSAIDs generally do not interact with corticosteroids. Renal clearance of salicylates is increased by corticosteroids, and withdrawal of corticosteroids may result in salicylate intoxication.
Corticosteroids reduce plasma salicylate concentrations, so this interaction may occur at pharmacological doses of glucocorticoids.
Phenytoin, ephedrine, rifabutin, carbamazepine, barbiturates, rifampicin, primidone, sympathomimetics and aminoglutethimide may increase the metabolic clearance of corticosteroids, resulting in decreased blood levels and decreased physiological activity, which may require adjustment of the corticosteroid dose.
International normalized ratio (INR) or prothrombin time should be monitored frequently in patients receiving corticosteroids and coumarin anticoagulants to avoid spontaneous bleeding, because of reports of altered response to these anticoagulants. Studies have shown that the usual effect of adding corticosteroids is to suppress the response to coumarins, although there are conflicting reports of enhanced effects, not supported by studies.
Ketoconazole monotherapy may suppress adrenal corticosteroid synthesis in the adrenal glands and cause adrenal insufficiency during corticosteroid withdrawal (see section "Special warnings and precautions for use").
Corticosteroids are antagonists of the effects of diuretics. Glucocorticosteroids are necessary for free renal clearance of water. When corticosteroids are used concomitantly with potassium-sparing diuretics (e.g., acetazolamide, loop diuretics, thiazides, carbenoxolone), patients should be carefully observed for hypokalemia.
Corticosteroids are antagonists of the hypotensive effects of beta-blockers, alpha-blockers, calcium channel blockers, clonidine, diazoxide, methyldopa, moxonidine, nitrates, nitroprusside, hydralazine, minoxidil, adrenergic neurone blockers, ACE inhibitors, and angiotensin II receptor antagonists.
Corticosteroids increase the risk of hypokalemia when used with cardiac glycosides, such as digoxin, theophylline, and beta-2-sympathomimetics, such as bambuterol, fenoterol, formoterol, ritodrine, salbutamol, salmeterol, and terbutaline.
There is an increased risk of hypokalemia when corticosteroids are used with amphotericin. Concomitant use of amphotericin with corticosteroids should be avoided unless amphotericin is necessary to control reactions.
The effect of corticosteroids may decrease within 3–4 days after interaction with mifepristone.
Plasma corticosteroid concentrations are increased by estrogen-containing oral contraceptives; dosage adjustment may be necessary if oral contraceptives are added to or removed from a stable regimen. Interactions are also possible with the use of contraceptive patches. Interactions are unlikely with low-dose hormone replacement therapy.
Plasma concentrations of corticosteroids may be increased by ritonavir.
Corticosteroids reduce the absorption of calcium salts.
Corticosteroid metabolism may be inhibited by erythromycin, except when small amounts of erythromycin are applied topically.
Corticosteroids are antagonists of the hypoglycemic effect of antidiabetic drugs.
There is an increased risk of hematological toxicity when corticosteroids are used with methotrexate.
Corticosteroids may inhibit the growth-enhancing effect of somatropin.
High doses of corticosteroids impair the immune response to vaccines—concurrent use with live vaccines should be avoided.
Corticosteroids are likely to reduce the effectiveness of sodium benzoate and sodium phenylbutyrate.
Concomitant use with CYP3A inhibitors, particularly cobicistat-containing products, is expected to increase the risk of systemic adverse reactions. This combination should be avoided unless the benefit outweighs the risk, in which case patients should be closely monitored for systemic corticosteroid adverse reactions.
Application features
Patients should keep a “Steroid Treatment” card, which will describe the precautions to be taken to minimize risks and contain detailed information on the prescription of the drug, dosage and duration of treatment.
The lowest dose of corticosteroids should be used and the dosage should be reduced if possible. The dosage should be reduced gradually.
Patients and/or healthcare professionals should be made aware of the potential for serious psychiatric adverse reactions that may occur with systemic steroids (see section 4.8). Symptoms usually appear within days or weeks of initiating treatment. The risks may be greater with high doses/systemic exposure (see also section 4.5 for pharmacokinetic interactions that may increase the risk of adverse reactions), as the dose level does not predict the initial onset, type, severity or duration of reactions. Most reactions resolve either after dose reduction or discontinuation of the drug, although specific treatment may be required.
Patients/caregivers should be encouraged to seek medical advice if psychological symptoms of concern develop, particularly if depressive mood or suicidal ideation is suspected. In addition, patients/caregivers should be aware of the potential for psychiatric disorders that may occur either during or immediately after dose reduction/withdrawal of systemic steroids, although such reactions have been reported to be uncommon.
The use of systemic corticosteroids should be considered with particular caution in patients with a history or current severe affective disorder in themselves or their first-degree relatives. Such disorders may include depressive or manic-depressive psychosis and a history of steroid psychosis.
The drug should be used with caution in patients with weakened immune systems.
Patients should be advised to take special precautions to avoid measles infection and to seek medical attention immediately if symptoms develop. Prophylactic measures such as intramuscular administration of normal immunoglobulin may be necessary.
Live vaccines should not be used in patients with suppressed immune responsiveness caused by high doses of corticosteroids. Inactivated vaccines or toxoids may be used, although their efficacy may be attenuated.
Corticosteroids should not be discontinued, and a dose reduction may be necessary. Corticosteroids may exacerbate systemic fungal infections and should not be used in the presence of such infections unless necessary to control life-threatening drug reactions due to amphotericin. In addition, cardiac enlargement and congestive heart failure have been reported following concomitant use of amphotericin and hydrocortisone.
Reports from scientific publications indicate a clear association between the use of corticosteroids and perforation of the left ventricular free wall after recent myocardial infarction, and therefore corticosteroid therapy should be used with great caution in such patients.
Moderate to high doses of hydrocortisone or cortisone may cause elevations in blood pressure, salt and water retention, and increased potassium excretion. These effects are less likely to occur with synthetic derivatives, except at high doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.
It is known that the use of corticosteroids in the cerebral form of malaria leads to prolonged coma and an increase in the frequency of pneumonia and gastrointestinal bleeding.
Because of the possibility of relapse, careful observation is necessary when prescribing corticosteroids to patients with latent tuberculosis or those who have a tuberculin reaction. During prolonged corticosteroid therapy, such patients should receive prophylactic chemotherapy.
The use of hydrocortisone tablets in active tuberculosis is prohibited, except in cases of progressive or disseminated tuberculosis.
Corticosteroids should be used with caution in renal failure, hypertension, diabetes mellitus or a family history of diabetes, congestive heart failure, thrombophlebitis, exanthematous disease, chronic nephritis, acute glomerulonephritis, metastatic carcinoma, osteoporosis (postmenopausal patients are at particular risk), severe affective disorders (especially if there is a history of steroid-induced psychosis), epilepsy, a history of steroid myopathy, hepatic failure, glaucoma (or a family history of glaucoma), myasthenia gravis, nonspecific ulcerative colitis with a risk of perforation, diverticulitis, recent intervention for enteroanastomosis, active or latent peptic ulcer. Signs of peritoneal irritation with subsequent gastrointestinal perforation may be minimal or absent in patients receiving high doses of corticosteroids.
During treatment, patients should be monitored for psychotic reactions, weakness, electrocardiogram changes, hypertension, and adverse hormonal changes.
Fat embolism has been reported as a complication of elevated cortisone levels.
The effect of corticosteroids is enhanced in patients with hypothyroidism and cirrhosis.
Prolonged use of corticosteroids increases the body's susceptibility to infections and their severity. In addition, the clinical manifestations of infections may be atypical.
Corticosteroids may mask some signs of infection, and certain serious infections, such as sepsis and tuberculosis, may progress to advanced stages without recognition. It may be impossible to localize the infection in patients taking corticosteroids. Corticosteroids may interfere with the nitroblue tetrazolium test for bacterial infections, resulting in false negative results.
Corticosteroids may activate latent amebiasis or strongyloidiasis or aggravate pre-existing disease. Therefore, it is recommended that latent or active amebiasis or strongyloidiasis be ruled out before initiating corticosteroid therapy in patients at risk or who present with symptoms suggestive of both diseases.
Prolonged use of corticosteroids may cause posterior subcapsular cataracts, glaucoma with possible optic nerve damage, and may exacerbate established secondary ocular infections caused by fungi or viruses.
Corticosteroids should be used with caution in patients with ocular herpes simplex due to the possibility of corneal perforation.
Hypertrophic cardiomyopathy has been reported following administration of hydrocortisone to premature infants, therefore appropriate diagnostic evaluation and monitoring of cardiac function and structure should be performed.
Visual disturbances are possible with the use of systemic and topical corticosteroids. If the patient presents with symptoms such as blurred vision or other visual disturbances, he or she should seek advice from an ophthalmologist to evaluate possible causes, which may include cataracts, glaucoma, and, rarely, central serous chorioretinopathy (CSCR), which has been reported following the use of systemic and topical corticosteroids.
Pheochromocytoma crisis
Pheochromocytoma crisis, which can be fatal, has been reported following the use of systemic corticosteroids. Corticosteroids should only be prescribed to patients with known or suspected pheochromocytoma after an appropriate risk/benefit assessment.
Corticosteroids may increase or decrease sperm motility and count. Diabetes may worsen, necessitating an increase in insulin dosage. Corticosteroids may cause latent diabetes mellitus to appear.
Women may experience menstrual irregularities, which patients should be informed about.
Anaphylactoid reactions have been observed rarely in patients receiving corticosteroids, particularly in those with a history of allergic reactions to drugs.
Aspirin should be used with caution in patients with hypoprothrombinemia when combined with corticosteroids.
Withdrawal syndrome. Too rapid withdrawal of corticosteroids may result in secondary adrenocortical insufficiency, which can be minimized by gradual dose reduction. This type of associated insufficiency may persist for several months after discontinuation of therapy, and any stressful event occurring during this period should prompt reinstatement of corticosteroid therapy. If the patient is already receiving steroids, the dosage should be increased. Since mineralocorticoid secretion may be impaired, salt and/or mineralocorticoid should be administered concomitantly (see section 4.5).
Discontinuation of corticosteroids after prolonged therapy may result in withdrawal symptoms including fever, myalgia, arthralgia, and malaise. Patients who have been receiving systemic corticosteroids at doses greater than physiologic (approximately 30 mg hydrocortisone) for more than 3 weeks should not discontinue the drug abruptly. The rate of dose reduction depends largely on the improvement in symptoms with a reduction in the dose of systemic corticosteroids. Clinical assessment of disease activity may be necessary when discontinuing the drug. If relapse is unlikely with discontinuation of systemic corticosteroids but there is uncertainty about hypothalamic-pituitary-adrenal suppression, the systemic corticosteroid dose may be rapidly reduced to physiologic doses. Once the dose reaches 30 mg of hydrocortisone per day, the dose reduction should be slowed to allow the hypothalamic-pituitary-adrenal axis to recover.
Abrupt withdrawal of systemic corticosteroid therapy for up to 3 weeks is acceptable if relapse is considered unlikely. Abrupt withdrawal of up to 160 mg of hydrocortisone for 3 weeks is unlikely to result in clinically relevant hypothalamic-pituitary-adrenal suppression in most patients. Gradual withdrawal of systemic corticosteroid therapy, even after courses of 3 weeks or less, is recommended for the following groups of patients:
patients who are taking a course of systemic corticosteroids repeatedly, particularly if the course lasts more than 3 weeks;
patients who are prescribed a short course of therapy within a year after discontinuation of a long course of therapy (over several months or years);
patients whose adrenocortical insufficiency has factors other than exogenous corticosteroid therapy;
patients taking systemic corticosteroid at a dose of more than 160 mg of hydrocortisone;
patients who repeat the dose in the evening.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
This medicinal product contains less than 1 mmol (23 mg) sodium per dose, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Corticosteroids administered to pregnant animals can cause fetal abnormalities, including cleft palate, intrauterine growth retardation, and effects on growth and brain development. There is no evidence that corticosteroids increase the incidence of hereditary abnormalities such as cleft palate/lip in humans. However, prolonged or repeated use of corticosteroids during pregnancy or repeated use during pregnancy increases the risk of intrauterine growth retardation. Pregnant patients should be carefully monitored for the development of fluid retention or preeclampsia. Theoretically, adrenal hypofunction may occur in the newborn after prenatal corticosteroid administration, but this usually resolves spontaneously after birth and is rarely clinically significant. As with other drugs, corticosteroids should be administered to mothers and children only if the benefits outweigh the risks. However, if corticosteroids are necessary, patients with normal pregnancies can take them in the same way as non-pregnant patients.
Corticosteroids are excreted in human milk, but data are not available for hydrocortisone. Some adrenal suppression may occur in infants whose mothers have been taking high doses of systemic corticosteroids for prolonged periods. Mothers receiving pharmacological doses of corticosteroids should be advised to discontinue breastfeeding. To facilitate follow-up, the mother's treatment should be carefully documented in the infant's medical record.
Ability to influence reaction speed when driving vehicles or other mechanisms
Hydrocortisone has a minor effect on the reaction rate when driving vehicles or other mechanisms.
Hydrocortisone may cause fatigue, dizziness, blurred vision, muscle atrophy and weakness. If the patient experiences such deterioration, he should refrain from driving or operating other machinery (see section "Adverse reactions").
Method of administration and doses
Method of application
For oral use.
Dosage
Dosage should be individualized according to the patient's response to treatment. The lowest possible dosage should be used. Doses should be in multiples of 10 (e.g., 10 mg, 20 mg, 30 mg, etc.).
Adverse reactions may be minimized by using the lowest effective dose for the shortest duration, as a single morning dose or, whenever possible, as a single morning dose every other day. Frequent monitoring of the patient is necessary to titrate the dose based on disease activity.
To avoid hypoadrenalism and/or relapse of the underlying disease, gradual discontinuation of the drug may be necessary (see section "Special warnings and precautions for use").
Replacement therapy
In chronic adrenocortical insufficiency, a dosage of 20 to 30 mg per day is usually recommended, sometimes together with 4–6 g of sodium chloride or 50–300 mcg of fludrocortisone daily.
If emergency care is indicated, one of the soluble adrenocorticotropic hormone preparations (e.g., dexamethasone sodium phosphate) can be life-saving, and can be effective within minutes of parenteral administration.
Elderly patients
Treatment of elderly patients, particularly long-term treatment, should be planned taking into account the more serious consequences of the common adverse reactions of corticosteroids in old age, especially osteoporosis, diabetes, hypertension, susceptibility to infections, and thinning of the skin.
For patients requiring replacement therapy, the daily dose should be given in two divided doses whenever possible. The first dose in the morning should be larger than the second dose in the evening, similar to the normal diurnal rhythm of cortisol secretion.
Use before surgery
The anesthesiologist should be informed that the patient is using corticosteroids or has used them in the past.
When long-term treatment is to be discontinued, the dosage should be gradually reduced over a period of several weeks or months depending on the dose and duration of therapy (see section "Special warnings and precautions for use").
Children
Replacement therapy
In chronic adrenal insufficiency, the dose should be approximately 0.4 to 0.8 mg/kg/day, divided into 2–3 doses, taking into account the needs of the individual child.
Use of the drug in serious injury or illness in patients with known adrenocortical insufficiency or questionable adrenal reserve
In general, doses are higher than those used in chronic adrenal insufficiency and should be determined according to the clinical situation.
Corticosteroids cause growth retardation in infants, children, and adolescents. Treatment should be limited to the lowest dose to minimize hypothalamic-pituitary-adrenal axis suppression and growth retardation. Growth and development should be closely monitored in infants and children receiving long-term corticosteroid therapy.
Overdose
Acute toxicity and/or fatal outcome following overdose of glucocorticoids have been reported rarely. There is no antidote.
Symptoms
Overdose can cause nausea and vomiting, sodium and water retention, hyperglycemia, and sometimes gastrointestinal bleeding.
Treatment
Treatment of reactions resulting from chronic poisoning is not indicated unless the patient has a condition that makes them particularly susceptible to adverse reactions to corticosteroids. In such cases, symptomatic treatment should be initiated, with cimetidine (200–400 mg by slow intravenous injection every 6 hours) or ranitidine (50 mg by slow intravenous injection every 6 hours) being used if necessary to prevent gastrointestinal bleeding.
Anaphylactic and hypersensitivity reactions can be treated with adrenaline, positive pressure ventilation and amnionophylline. The patient should be kept warm and at rest.
The biological half-life of hydrocortisone is approximately 100 minutes.
Side effects
The frequency of expected adverse reactions, in particular hypothalamic-pituitary-adrenal axis suppression, correlates with the relative potency of the drug, dosage, time of administration and duration of treatment (see section "Special warnings and precautions for use").
The following are adverse reactions that may be associated with long-term systemic use of corticosteroids. The frequency of these adverse reactions is unknown (cannot be estimated from the available data).
Organ systems
Adverse reactions
Infections and infestations
Infection*
Blood and lymphatic system disorders
Leukocytosis
On the part of the immune system
Hypersensitivity, including anaphylaxis
From the endocrine system
Increased or decreased sperm motility and count, irregular menstruation, amenorrhea, development of Cushingoid syndrome, secondary adrenal insufficiency (particularly during stress such as trauma, surgery or disease), decreased carbohydrate tolerance, manifestations of latent diabetes mellitus, hyperglycemia, increased need for insulin or oral antidiabetic agents in diabetes, hirsutism
Metabolic and nutritional disorders
Sodium retention, fluid retention, hypokalemia, hypokalemic alkalosis, increased calcium excretion, negative nitrogen balance due to protein catabolism, increased appetite
From the psyche
Psychiatric disorders, psychological dependence, depression, insomnia. A wide range of psychiatric reactions, including affective disorders (such as irritability, euphoria, depression and mood swings, suicidal ideation), psychotic reactions (mania, delusions, hallucinations and exacerbation of schizophrenia), exacerbation of epilepsy, behavioral disorders, irritability, anxiety, sleep disorders and cognitive dysfunction, including confusion and amnesia**.
From the nervous system
Convulsions, increased intracranial pressure with optic disc edema (pseudotumor cerebri), usually after treatment, vertigo, headache, malaise
From the organs of vision
Posterior subcapsular cataract, increased intraocular pressure, optic disc edema, thinning of the cornea or sclera, exacerbation of viral or fungal eye disease, glaucoma, exophthalmos, blurred vision (see also section "Special warnings and precautions for use")
From the heart
Myocardial rupture after myocardial infarction (see section "Special warnings and precautions for use"), congestive heart failure in vulnerable patients
From the vascular side
Thromboembolism, hypertension, hypertrophic cardiomyopathy in premature infants
Respiratory, thoracic and mediastinal disorders
Hiccup
Gastrointestinal tract
Gastric and duodenal ulcers with possible perforation and bleeding, perforation of the small and large intestines, especially in patients with inflammatory bowel disease, pancreatitis, abdominal distension, ulcerative esophagitis, dyspepsia, esophageal candidiasis, nausea
Skin and subcutaneous tissue disorders
Impaired wound healing, thin, fragile skin, petechiae and ecchymoses, erythema, stretch marks, acne, increased sweating, suppression of skin test reactions, other skin reactions such as allergic dermatitis, urticaria, angioedema
Musculoskeletal and connective tissue disorders
Muscle weakness, steroid myopathy, muscle wasting, osteoporosis (especially in postmenopausal women), vertebral compression fractures, aseptic necrosis of the humeral and femoral heads, pathological fracture of long bones, avascular osteonecrosis, tendon rupture
Research
Weight gain
* Increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections and relapse of latent tuberculosis (see section "Special instructions").
** Reactions are common and can occur in adults and children. In adults, the incidence of severe reactions is 5–6%. Psychological effects have been reported when corticosteroids are withdrawn.
Pediatric population
Growth suppression in infants, children and adolescents, increased intracranial pressure with optic disc swelling in children (pseudotumor cerebri), usually after discontinuation of treatment.
Withdrawal symptoms
Too rapid a reduction in the dose of a corticosteroid after prolonged treatment can lead to acute renal failure, hypotension and death (see section "Special instructions"). Withdrawal syndrome may also occur, including high fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules, and weight loss.
Reporting of suspected adverse reactions
Reporting adverse reactions after registration of a medicinal product is of great importance. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of a medicinal product via the Automated Information System for Pharmacovigilance at https//aisf.dec.gov.ua.
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 30 ° C. Keep out of the reach of children.
Packaging
10 tablets in a blister; 6 or 18 blisters in a pack.
Vacation category
According to the recipe.
Producer
mibe GmbH Arcnaymittel.
Location of the manufacturer and address of its place of business.
