Ziflucort (Tablets) Instructions for Use

Marketing Authorization Holder

Pharmasintez-Tyumen, LLC (Russia)

ATC Code

H02AA02 (Fludrocortisone)

Active Substance

Fludrocortisone (Rec.INN registered by WHO)

Dosage Form

Ziflucort

Tablets 0.1 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Tablets are white or almost white, round, biconvex; marbling of the color is allowed.

Excipients: microcrystalline cellulose type 200 – 189.9 mg, povidone K25 – 8 mg, colloidal silicon dioxide – 1 mg, magnesium stearate – 1 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – polymer jars (1) – cardboard packs.
20 pcs. – polymer jars (1) – cardboard packs.

Clinical-Pharmacological Group

Adrenal cortex hormone. Mineralocorticoid

Pharmacotherapeutic Group

Mineralocorticosteroid

Pharmacological Action

A corticosteroid with pronounced mineralocorticoid activity and glucocorticoid activity.

The mineralocorticoid action is due to binding with mineralocorticoid receptors in the cytoplasm of target cells, primarily in the cells of the renal collecting tubules. As a result, sodium reabsorption increases, and potassium and hydrogen are excreted, while water retention is observed. Sodium reabsorption also increases in the sweat and salivary glands, the gastrointestinal mucosa, and through cell membranes.

Possessing glucocorticoid activity, Fludrocortisone suppresses the functions of leukocytes and tissue macrophages. It limits the migration of leukocytes to the area of inflammation. It impairs the ability of macrophages to phagocytose and to form interleukin-1. It promotes the stabilization of lysosomal membranes, thereby reducing the concentration of proteolytic enzymes in the area of inflammation. It reduces capillary permeability caused by the release of histamine. It suppresses fibroblast activity and collagen formation.

Fludrocortisone inhibits the activity of phospholipase A₂, which leads to the suppression of prostaglandin and leukotriene synthesis; it suppresses the release of COX (mainly COX-2), which also contributes to the reduction of prostaglandin production.

It reduces the number of circulating lymphocytes (T- and B-cells), monocytes, eosinophils, and basophils due to their movement from the vascular bed into the lymphoid tissue; it suppresses antibody formation.

Fludrocortisone suppresses the release of ACTH and β-lipotropin by the pituitary gland but does not reduce the level of circulating β-endorphin; it inhibits the secretion of TSH and FSH.

When applied directly to blood vessels, it causes a vasoconstrictor effect.

It stimulates gluconeogenesis, promotes the uptake of amino acids by the liver and kidneys, and increases the activity of gluconeogenesis enzymes. In the liver, Fludrocortisone enhances glycogen storage by stimulating the activity of glycogen synthase and the synthesis of glucose from protein metabolism products. The increase in blood glucose levels activates insulin secretion.

It suppresses glucose uptake by fat cells, which leads to the activation of lipolysis. However, due to increased insulin secretion, lipogenesis is stimulated, leading to fat accumulation.

It has a catabolic effect in lymphoid and connective tissue, muscles, adipose tissue, skin, and bone tissue. As a result of the catabolic action, growth suppression in children is possible.

In high doses, Fludrocortisone may increase the excitability of brain tissues and contribute to a lowering of the seizure threshold. It stimulates excessive production of hydrochloric acid and pepsin in the stomach, which contributes to the development of peptic ulcers.

Compared to hydrocortisone, the ability of fludrocortisone to retain sodium ions in the body is 250 times stronger, and its anti-inflammatory activity is 10 times stronger.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. The C_max of fludrocortisone in plasma is reached in approximately 2 hours. Plasma protein binding is 42%.

It is metabolized in the liver. T_1/2 is about 3.5 hours. It is excreted by the kidneys as inactive metabolites.

Indications

Primary adrenocortical insufficiency (Addison’s disease, condition after total adrenalectomy); secondary adrenocortical insufficiency; adrenogenital syndrome (congenital adrenal hyperplasia); hypovolemia and arterial hypotension of various origins.

ICD codes

Dosage Regimen

Establish the dosage individually based on the indication, therapeutic response, and the patient’s clinical condition.

For primary adrenocortical insufficiency (Addison’s disease), the typical adult dosage is 0.05 mg to 0.2 mg once daily. Administer concurrently with a glucocorticoid, such as hydrocortisone or cortisone.

For adrenogenital syndrome, administer 0.1 mg to 0.2 mg once daily.

For the management of salt-losing forms of adrenogenital syndrome, the typical dosage is 0.05 mg to 0.1 mg daily.

Adjust the dosage for pediatric patients based on body surface area or body weight. Closely monitor growth and development during long-term therapy.

During periods of physiological stress, such as surgery, trauma, or infection, increase the dosage. Parenteral administration of mineralocorticoids may be necessary.

Monitor blood pressure, body weight, and serum electrolytes regularly to guide dosage adjustments and prevent fluid overload or hypokalemia.

Restrict dietary sodium intake to mitigate the risk of edema and hypertension.

When discontinuing treatment, taper the dose gradually to avoid acute adrenocortical insufficiency or withdrawal syndrome.

In geriatric patients or those with hepatic or renal impairment, use with caution and initiate therapy at the lower end of the dosage range.

Adverse Reactions

From the endocrine system: suppression of ACTH production, increased blood glucose levels, menstrual cycle disorders are possible.

From the metabolic side: suppression of protein synthesis, slowed growth in children, edema are possible.

From the digestive system: erosive-ulcerative lesions of the gastrointestinal tract are possible.

Other: skin rash, increased blood pressure are possible.

With topical application: increased intraocular pressure, formation of subcapsular cataract are possible.

Contraindications

Hypersensitivity to fludrocortisone; systemic fungal infections.

With caution

In ulcerative colitis, intestinal diverticulosis, gastric or duodenal ulcer, acute or latent peptic ulcer, recently created intestinal anastomoses, esophagitis, gastritis, history of gastrointestinal surgery, impaired liver function, renal failure, arterial hypertension, osteoporosis, myasthenia gravis, hypoalbuminemia and conditions predisposing to its occurrence, hyperlipidemia; in diabetes mellitus (including impaired carbohydrate tolerance), hypothyroidism, Cushing’s disease, thyrotoxicosis, obesity (grade III-IV), acute psychosis and mental disorders, poliomyelitis (except for the form of bulbar encephalitis).

Caution should be exercised when treating patients with cardiovascular diseases, including after a recent myocardial infarction (in patients with acute and subacute myocardial infarction, the spread of the necrosis focus, slowing of scar tissue formation, and, as a result, rupture of the heart muscle are possible), decompensated chronic heart failure.

It is prescribed with caution in parasitic and infectious diseases (current or recently suffered, including recent contact with a patient) – herpes simplex, herpes zoster (viremic phase), chickenpox, measles, amoebiasis, strongyloidiasis (established or suspected); active and latent tuberculosis. Use in severe infectious diseases is permissible only against the background of specific antimicrobial therapy.

Caution should be exercised when treating patients in the post-vaccination period (a period of 8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination.

The decision to use mineralocorticosteroids in patients with HIV infection and AIDS should be made after a careful assessment of the expected benefit and potential risk.

Use in Pregnancy and Lactation

Use during pregnancy or in women planning pregnancy is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus. If use during lactation is necessary, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

It should be used with caution in patients with impaired liver function.

Use in Renal Impairment

It should be used with caution in patients with renal failure.

Pediatric Use

Use in children is possible according to indications, in age-appropriate recommended doses and regimens. Careful monitoring of adrenal cortex function is necessary in newborns and older children whose mothers received Fludrocortisone during pregnancy. During long-term treatment of children, their growth and development should be monitored.

Geriatric Use

It should be prescribed with caution to elderly patients to avoid worsening of concomitant diseases.

Special Precautions

During treatment, patients with diabetes mellitus require regular monitoring of blood glucose levels.

During long-term treatment, monitoring of blood potassium levels is necessary.

In case of stressful situations, patients taking Fludrocortisone are recommended parenteral administration of mineralocorticosteroids.

Sudden discontinuation of treatment may cause the development of acute adrenocortical insufficiency, so the dose of fludrocortisone should be reduced gradually.

With sudden withdrawal of fludrocortisone, especially after long-term use, a “withdrawal” syndrome may develop, manifested by anorexia, fever, muscle and joint pain, and general weakness. These symptoms may appear even in the absence of adrenocortical insufficiency.

Fludrocortisone may mask the symptoms of infection, reduce resistance to infection and the ability to localize it.

Long-term use of fludrocortisone increases the risk of developing secondary fungal or viral infections.

Patients taking Fludrocortisone should not be vaccinated with live virus vaccines. The administration of an inactivated viral or bacterial vaccine may not cause the expected increase in the number of antibodies. Furthermore, in patients taking mineralocorticosteroids, there is an increased risk of neurological complications during vaccination.

The effect of fludrocortisone is enhanced in patients with hypothyroidism or liver cirrhosis.

When treating patients with hypoprothrombinemia, Fludrocortisone and acetylsalicylic acid should be prescribed concurrently with caution.

During the use of fludrocortisone, to avoid the appearance of edema and increased blood pressure, it is necessary to limit salt intake with food.

Drug Interactions

With the simultaneous use of fludrocortisone and cardiac glycosides, the risk of cardiac arrhythmias and glycoside toxicity associated with hypokalemia increases.

With simultaneous use, barbiturates, antiepileptic drugs (phenytoin, carbamazepine), rifampicin, glutethimide accelerate the metabolism of mineralocorticosteroids (by inducing microsomal enzymes) and weaken their effect.

With simultaneous use, antihistamines weaken the effect of fludrocortisone.

With simultaneous use of fludrocortisone and amphotericin B, carbonic anhydrase inhibitors, hypokalemia, left ventricular hypertrophy, and circulatory failure are possible.

With simultaneous use of fludrocortisone and anabolic steroids, androgens, the risk of developing peripheral edema and acne increases.

With simultaneous use of oral contraceptive preparations containing estrogens, the concentration of globulins that bind mineralocorticosteroids in the blood serum increases, metabolism slows down, the half-life increases, and the effect of fludrocortisone is enhanced.

With simultaneous use of fludrocortisone and anticoagulants (coumarin derivatives, indandione, heparin), streptokinase, urokinase, a decrease, and in some patients an increase in effectiveness is possible; the dose should be determined based on prothrombin time; the risk of ulcer formation and gastrointestinal bleeding increases.

With simultaneous use of fludrocortisone and tricyclic antidepressants, an increase in mental disorders associated with the use of fludrocortisone is possible.

With simultaneous use of fludrocortisone and oral hypoglycemic drugs, insulin, a weakening of the hypoglycemic effect and an increase in blood glucose concentration are possible.

With simultaneous use of fludrocortisone and potassium-sparing diuretics, the effect of the latter is weakened, and hypokalemia occurs.

With simultaneous use, ephedrine may accelerate the metabolism of mineralocorticosteroids.

With simultaneous use of fludrocortisone and immunosuppressive drugs, the risk of developing infections, lymphoma, and other lymphoproliferative diseases increases.

With simultaneous use of fludrocortisone and drugs that block neuromuscular conduction (depolarizing muscle relaxants), hypocalcemia associated with the use of fludrocortisone can enhance synaptic blockade, leading to an increase in the duration of neuromuscular blockade.

With simultaneous use of fludrocortisone and NSAIDs, acetylsalicylic acid, a weakening of the effect and an increased risk of developing peptic ulcers and gastrointestinal bleeding are possible.

With simultaneous use of fludrocortisone and vaccines containing live viruses, virus replication and the development of diseases are possible; antibody production is reduced. When using other vaccines, the risk of neurological complications and reduced antibody production increases.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.