Instructions for use Cortineff tablets 0.1 mg bottle No. 20
Composition
active ingredient: fludrocortisone acetate;
1 tablet contains 0.1 mg of fludrocortisone acetate;
excipients: lactose monohydrate, potato starch, gelatin, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white tablets with a cream tint, round, beveled on both sides, with smooth surfaces and solid edges, engraved with the letter “F” on one side, “−” on the other.
Pharmacotherapeutic group
Corticosteroids for systemic use. Mineralocorticoids. ATC code H02A A02.
Pharmacological properties
Pharmacodynamics.
Cortineff (fludrocortisone) is a synthetic adrenal cortex hormone, a fluorinated derivative of hydrocortisone with a strong mineralocorticotropic effect. Inflammatory diseases are not indications for the use of fludrocortisone.
Fludrocortisone acts on the distal renal tubule, stimulating sodium reabsorption and water retention, and increasing potassium and hydrogen ion excretion. Fludrocortisone can inhibit adrenal cortex function, thyroid activity, and pituitary ACTH secretion. It can also stimulate glycogen deposition in the liver, reduce the number of eosinophilic granulocytes, and can lead to a negative nitrogen balance.
Pharmacokinetics.
After oral administration, fludrocortisone is rapidly and completely absorbed from the gastrointestinal tract. Studies in humans and animals after intravenous and duodenal administration have shown that, depending on the species, 50% or more of the steroid remains unchanged 30 minutes after administration. After administration in the form of acetate, only the unesterified alcohol can be detected in the blood. The blood concentration reaches its highest value between 4 and 8 hours. The maximum serum concentration in healthy volunteers after intravenous administration is observed approximately 1.7 hours after administration.
The elimination half-life after intravenous administration in animals and healthy volunteers is 30 minutes. Following acetate administration to animals, a three-phase decline in blood concentrations was observed, each phase possibly corresponding to the elimination of the metabolite.
Fludrocortisone is 70-80% bound to plasma proteins, mainly to the globulin fraction. In healthy volunteers, 80% is excreted in the urine, and the remaining 20% by other routes. As with the metabolism of other steroids, biliary excretion is balanced by intestinal absorption, and a small amount is excreted in the feces.
Indication
Replacement therapy for primary and secondary adrenal insufficiency in Addison's disease. Treatment of adrenogenital syndrome with salt wasting syndrome.
Contraindication
Hypersensitivity to fludrocortisone or to any component of the drug. Systemic infection, if not treated specifically.
Interaction with other medicinal products and other types of interactions
With simultaneous use of Cortineff:
with barbiturates, antiepileptic drugs (phenytoin, carbamazepine), rifampicin, rifabutin, primidone, aminoglutathione, antihistamines, the effect of fludrocortisone is weakened due to the induction of microsomal enzymes;
with anabolic steroids, androgens, the risk of edema and rashes increases;
with amphotericin injections and drugs that reduce potassium levels: patients should be monitored for hypokalemia;
Anticholinesterases: the effect of interaction with anticholinesterase drugs may be antagonistic;
Oral anticoagulants: corticosteroids may potentially reduce anticoagulant effects;
Antihypertensive drugs, including diuretics: corticosteroids have an antagonistic effect on antihypertensive drugs and diuretics; the hypokalemic effect of diuretics, including acetazolamide, is enhanced;
antituberculosis drugs: serum concentrations of isoniazid may decrease;
Cyclosporine: Monitor for evidence of increased cyclosporine toxicity with concomitant use of these drugs.
Digitalis glycosides: simultaneous use may increase the toxicity of digitalis;
with oral contraceptives containing estrogens, the metabolism slows down and the effect of fludrocortisone increases;
Liver enzyme inducers: (aminoglutemide, barbiturates, carbamazepine, phenytoin, primidone, rifabutin, rifampicin): may increase metabolic clearance. Patients should be monitored for possible reduction in steroid effects, dosage should be adjusted accordingly;
human growth hormones: possible inhibitory effect on the action of the hormone;
Ketoconazole: clearance of the corticosteroid may be reduced, leading to increased effects;
depolarizing muscle relaxants: corticosteroids may reduce or increase neuromuscular blocking effects;
with antithrombotic agents (coumarin derivatives, indadione, heparin, streptokinase, urokinase) decreases, and in some individuals, the effectiveness of these drugs increases.
The dose should be prescribed taking into account prothrombin time indicators;
with oral antidiabetic drugs, insulin - weakening of the antidiabetic effect;
with diuretics - the effect of diuretics decreases, hypokalemia, weakening of the effect of laxatives;
with nonsteroidal anti-inflammatory drugs, the risk of developing ulcers and bleeding from the gastrointestinal tract increases;
with medications and products containing sodium - edema, increased blood pressure; it may be necessary to limit sodium in the diet, as well as medications with a high sodium content; the use of corticosteroids sometimes requires additional sodium intake.
Antihistamine medications reduce the effectiveness of fludrocortisone.
With the simultaneous use of vaccines containing live viruses and immunosuppressive doses of glucocorticosteroids, the development of viral diseases and a decrease in the effectiveness of the vaccine are possible.
Concomitant administration of glucocorticoids and CYP3A inhibitors, including products containing cobicistat, is expected to increase the risk of systemic adverse reactions. Such interactions should be avoided unless the benefit outweighs the increased risk of systemic adverse reactions associated with glucocorticoids. In such cases, the patient should be monitored for systemic effects of glucocorticoids.
Possible systemic effects include: Cushing's syndrome, Cushingoid syndrome, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma.
Salicylates: Corticosteroids may reduce serum salicylate levels and reduce their effectiveness. Conversely, discontinuation of corticosteroid therapy during high-dose salicylate therapy may result in salicylate toxicity.
Application features
Due to the strong mineralocorticoid effect of fludrocortisone, salt intake and intake should be monitored to prevent the risk of hypertension, edema, or weight gain. With prolonged use of the drug, periodic monitoring of serum electrolyte levels is recommended. Due to the risk associated with sodium retention, Cortineff should be used only when indicated.
Cortineff is a potent mineralocorticoid drug and should be used primarily in replacement therapy. Any side effects that may occur with the drug may be reduced with appropriate dose adjustment.
With prolonged use of fludrocortisone, adrenocorticotropic atrophy develops, which may occur even for several years after discontinuation of treatment. Withdrawal of corticosteroid therapy should be carried out according to a long-term scheme, which should be gradual to prevent the risk of adrenocorticoid insufficiency. In stressful situations (trauma, surgery), patients receiving long-term therapy should be supplemented with corrective corticosteroid therapy, which should be continued together with Cortineff therapy and for several years after its completion.
Fludrocortisone may mask the symptoms of infection, reducing resistance to infection and the ability to localize it.
Patients taking medications that suppress the immune system are more susceptible to infection than healthy patients. Chickenpox, shingles, and measles may be more severe when treated with corticosteroids. Patients who have not had these diseases before should avoid contact with sick people.
Patients who have not had chickenpox and are taking oral corticosteroids for reasons other than replacement therapy should be considered at risk for severe chickenpox. Exacerbations of diseases such as pneumonia, hepatitis, and disseminated intravascular coagulation may occur.
After exposure to a person with chickenpox, administration of Varicella zoster immunoglobulin (VZIG) is indicated for patients who are currently taking corticosteroids or who have taken them within three months prior to exposure. VZIG should be administered for
3 days, but no later than 10 days after contact with a person with chickenpox. Do not stop taking corticosteroids, but increase their dose. Immune globulin (IG) should be administered after contact with a person with measles.
Patients treated with fludrocortisone should not be vaccinated with live viral vaccines.
The use of an inactivated bacterial or viral vaccine may not produce the expected increase in antibodies.
Special precautions.
Given that Cortineff is intended for long-term use primarily as replacement therapy, to reduce side effects that may occur due to glucocorticotropic action, it should be used in the lowest effective doses.
The effects of corticosteroids may be enhanced in patients with hypothyroidism or diminished in patients with hyperthyroidism.
Fludrocortisone should be used with caution in cases of chronic nephritis or renal failure, osteoporosis (especially in postmenopausal women), active peptic ulcer or its remission, myasthenia gravis, fungal or viral infections, local or systemic, glaucoma (or glaucoma in the family history), hyperlipidemia, hypoalbuminemia.
The use of fludrocortisone in patients with active tuberculosis should be limited to cases of disseminated or rapidly progressing tuberculosis and only in combination with antituberculosis therapy. Patients with latent tuberculosis or positive tuberculin skin test who are receiving fludrocortisone should be monitored for the risk of developing tuberculosis. Patients on long-term corticosteroid therapy should receive prophylactic antituberculosis drugs.
Fludrocortisone should be used with caution in patients with hypertension, congestive heart failure, steroid myopathy, epilepsy, impaired liver function, and acute psychosis and psychiatric disorders. Pre-existing emotional lability or psychotic disorders may be exacerbated by fludrocortisone. Fludrocortisone is more potent in patients with thyroid insufficiency or cirrhosis.
Patients or their caregivers should be warned about the potentially serious psychiatric adverse reactions that can occur with the use of systemic steroids. These symptoms may occur within days or weeks of starting treatment. The risk may be higher with higher doses and systemic exposure, although dose levels do not predict the onset, type, severity or duration of reactions. Most reactions are reversible upon dose reduction or discontinuation of the drug, although specific treatment may be necessary. Patients or their caregivers should not hesitate to seek medical advice if they develop psychological symptoms that concern them, especially depressed mood or suicidal ideation. Patients or their caregivers should be warned
about possible psychiatric disorders that may occur either during or immediately after dose adjustment of systemic steroids, as such reactions have been reported infrequently.
Caution should also be exercised in patients with a current or previous history of severe affective disorders or their first-degree relatives when using systemic corticosteroids in terms of depressive or manic-depressive illnesses and previous steroid psychoses.
Diabetic patients may experience worsening of their condition, requiring higher doses of insulin. Fludrocortisone may cause the manifestation of latent diabetes mellitus.
Women are at risk of irregular menstrual bleeding.
Infants born to mothers who have taken high doses of corticosteroids during pregnancy or while breastfeeding should be monitored for possible adrenal insufficiency. Growth and development may be impaired in children who have been taking corticosteroids for a long time.
Patients with hypoprothrombinemia should be cautious when taking acetylsalicylic acid in combination with fludrocortisone.
In rare cases, anaphylactic reactions may occur in patients taking corticosteroids, especially in cases of previously confirmed hypersensitivity to drugs.
Cortineff contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Visual disturbances. Visual disturbances may occur with systemic and topical corticosteroids. If a patient experiences symptoms such as blurred vision or other visual problems, consideration should be given to consulting an ophthalmologist to rule out possible causes such as cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR), which has been reported with systemic and topical corticosteroids.
Use during pregnancy or breastfeeding
Fludrocortisone is contraindicated in women of reproductive age and during pregnancy unless absolutely necessary. Patients who develop preeclampsia and fluid retention should be closely monitored by a physician.
There may be a small risk of cleft palate and intrauterine growth retardation. Hypoadrenalism (hypofunction of the adrenal glands) may occur in the newborn. Newborns of mothers who have received large doses of corticosteroids during pregnancy or while breastfeeding should be carefully observed for signs of adrenal hypofunction.
Fludrocortisone passes into breast milk and may cause adverse reactions in the child: growth retardation or suppression of the secretion of endogenous adrenal cortex hormones, therefore breastfeeding should be discontinued during treatment.
Ability to influence reaction speed when driving vehicles or other mechanisms
There is no data regarding the impact on the psychophysical state of a person and the speed of neuromotor reactions.
Method of administration and doses
The dose of the drug should be selected individually, depending on the severity of the disease and the response to therapy. During treatment, it may be necessary to change the dose depending on the course of the disease or in a stressful situation such as surgery, trauma or infectious disease.
For adults: The usual recommended dose is 0.1 mg to 0.3 mg (1–3 tablets) per day. The tablets should not be divided.
If a dose is missed, take it as soon as possible or, if it is almost time for the next dose, skip the missed dose and continue with the prescribed treatment regimen. Do not take two doses at the same time.
Elderly patients: no dose adjustment is required.
Children
Safety and efficacy in children have not been officially established, so the drug should not be used in pediatric practice.
Overdose
Monitoring of serum electrolyte concentrations is necessary. Potassium chloride administration and dietary sodium restriction should be considered. In the event of a large single dose of fludrocortisone, large amounts of water should be taken. Monitoring of serum electrolyte concentrations is necessary to prevent overdose. Potassium chloride administration and dietary sodium restriction should be considered.
Side effects
Fludrocortisone may mask the symptoms of infections, reduce their intensity, reduce immunity to infections and the ability to localize them.
Most of the side effects are related to the mineralocorticotropic action of fludrocortisone, including water and electrolyte disturbances: sodium and fluid retention, hypertension, edema, congestive heart failure, potassium loss, hypokalemic alkalosis, arrhythmias or ECG changes associated with potassium deficiency, and increased calcium excretion. Short-term use of fludrocortisone, like other corticosteroids, only sporadically causes side effects related to glucocorticotropic activity. The risk of developing the following side effects primarily concerns patients taking fludrocortisone for a long time or simultaneously with other corticosteroids.
Musculoskeletal system: muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, compression fractures of the spine, aseptic necrosis of the femoral and humeral heads, pathological fractures of long bones, tendon rupture, avascular osteonecrosis.
Gastrointestinal: peptic ulcer and its consequences: bleeding, perforation of the esophagus, stomach and duodenum, perforation of the large or small intestine, especially in patients with intestinal inflammation; inflammation of the pancreas; bloating; ulcerative inflammation of the esophagus, indigestion; candidiasis, excessive appetite.
Skin: rash, delayed wound healing; thinning of the skin; ecchymoses and hematomas; erythema; excessive sweating, purpura, atrophic skin stripes, acne, skin manifestations resembling changes characteristic of systemic lupus erythematosus, decreased skin test response, hirsutism.
Nervous system: euphoria, personality disorders, depression, sleep disorders, convulsions; increased intracranial pressure with papillary edema (pseudotumor cerebri - usually after too rapid a dose reduction); dizziness and headache, neuritis or paresthesias, increased symptoms of psychosis, epilepsy.
Endocrine disorders: irregular menstruation or amenorrhea; development of Cushing's syndrome; growth retardation in children; secondary insufficiency of the adrenal cortex and pituitary gland, especially in stressful situations (illness, trauma, surgery), decreased tolerance to carbohydrates; manifest diabetes mellitus and increased need for insulin and antidiabetic drugs in patients with existing diabetes mellitus, hirsutism, weight gain, negative protein and calcium balance, excessive appetite.
On the part of the organs of vision: posterior subcapsular cataract; increased intraocular pressure; glaucoma; exophthalmos, thinning of the cornea or sclera, exacerbation of eye diseases of fungal and viral etiology, blurred visual perception.
Other disorders: necrotizing vasculitis or lymphangitis, thrombophlebitis and obliterating endarteritis, leukocytosis, insomnia, allergic reactions, anaphylactic reactions, angioedema, pruritus, urticaria, vertigo, papilloedema.
Symptoms and signs of withdrawal syndrome: fever, myalgia, arthralgia, rhinitis, conjunctivitis; painful, itchy skin thickening; weight loss. Too rapid withdrawal of the dose after prolonged use can lead to acute adrenal insufficiency, hypotension and death.
Expiration date
3 years. Do not take the medicine after the expiry date stated on the package.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C, protected from light and moisture, out of the reach of children.
Packaging
20 tablets in an orange glass bottle with a polyethylene stopper, 1 bottle in a cardboard box.
20 tablets in a blister, 1 blister of PVC/Al foil, in a cardboard box.
Vacation category
According to the recipe.
Producer
Adamed Pharma SA, Poland.
Address
ul. Marsz. J. Pilsudskiego 5, Pabianice, 95 – 200, Poland.
