Label: FLUDROCORTISONE ACETATE tablet

Fludrocortisone acetate tablets, USP 0.1 mg contain fludrocortisone acetate, a synthetic adrenocortical steroid possessing very potent mineralocorticoid properties and high glucocorticoid activity; it is used only for its mineralocorticoid effects. The chemical name for fludrocortisone acetate is 9-fluoro-11β, 17, 21-trihydroxypregn-4-ene-3, 20-dione 21-acetate; its structural formula is:

C23H31FO6                       MW 422.50

Fludrocortisone acetate tablets, USP 0.1 mg are available for oral administration as scored tablets providing 0.1 mg fludrocortisone acetate per tablet. Inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, and microcrystalline cellulose.

Corticosteroids are thought to act at least in part, by controlling the rate of synthesis of proteins. Although there are a number of instances in which the synthesis of specific proteins is known to be induced by corticosteroids, the links between the initial actions of the hormones and the final metabolic effects have not been completely elucidated.

The physiologic action of fludrocortisone acetate is similar to that of hydrocortisone. However, the effects of fludrocortisone acetate, particularly on electrolyte balance, but also on carbohydrate metabolism, are considerably heightened and prolonged. Mineralocorticoids act on the distal tubules of the kidney to enhance the reabsorption of sodium ions from the tubular fluid into the plasma; they increase the urinary excretion of both potassium and hydrogen ions. The consequence of these three primary effects together with similar actions on cation transport in other tissues appear to account for the entire spectrum of physiological activities that are characteristic of mineralocorticoids. In small oral doses, fludrocortisone acetate produces marked sodium retention and increased urinary potassium excretion. It also causes a rise in blood pressure, apparently because of these effects on electrolyte levels.

In larger doses, fludrocortisone acetate inhibits endogenous adrenal cortical secretion, thymic activity, and pituitary corticotropin excretion; promotes the deposition of liver glycogen; and, unless protein intake is adequate, induces negative nitrogen balance.

The approximate plasma half-life of fludrocortisone (fluorohydrocortisone) is 3.5 hours or more and the biological half-life is 18 to 36 hours.

Fludrocortisone acetate tablets are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison's disease and for the treatment of salt-losing adrenogenital syndrome.

Corticosteroids are contraindicated in patients with systemic fungal infections and in those with a history of possible or known hypersensitivity to these agents.

BECAUSE OF ITS MARKED EFFECT ON SODIUM RETENTION THE USE OF FLUDROCORTISONE ACETATE IN THE TREATMENT OF CONDITIONS OTHER THAN THOSE INDICATED HEREIN IS NOT ADVISED.

Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. If an infection occurs during fludrocortisone acetate therapy, it should be promptly controlled by suitable antimicrobial therapy.

Prolonged use of corticosteroids may produce posterior sub capsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.

Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. However, since fludrocortisone acetate is a potent mineralocorticoid, both the dosage and salt intake should be carefully monitored in order to avoid the development of hypertension, edema or weight gain. Periodic checking of serum electrolyte levels is advisable during prolonged therapy; dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.

Patients should not be vaccinated against smallpox while on corticosteroid therapy. Other immunization procedures should not be undertaken in patients who are on corticosteroids, especially on high dose, because of possible hazards of neurological complications and a lack of antibody response.

The use of fludrocortisone acetate in patients with active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary since reactivation of the disease may occur. During prolonged corticosteroid therapy these patients should receive chemoprophylaxis.

Children who are on immunosuppressant drugs are more susceptible to infections than healthy children. Chicken pox and measles, for example, can have a more serious or even fatal course in children on immunosuppressant corticosteroids. In such children, or in adults who have not had these diseases, particular care should be taken to avoid exposure. If exposed, therapy with variicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If chicken pox develops, treatment with antiviral agents may be considered.

Most adverse reactions are caused by the drug's mineralocorticoid activity (retention of sodium and water) and include hypertension, edema, cardiac enlargement, congestive heart failure, potassium loss, and hypokalemic alkalosis.

When fludrocortisone is used in the small dosages recommended, the glucocorticoid side effects often seen with cortisone and its derivatives are not usually a problem; however, the following untoward effects should be kept in mind, particularly when fludrocortisone is used over a prolonged period of time or in conjunction with cortisone or a similar glucocorticoid.

Musculoskeletal—muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, pathologic fracture of long bones, and spontaneous fractures.

Gastrointestinal—peptic ulcer with possible perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis.

Dermatologic—impaired wound healing, thin fragile skin, bruising, petechiae and ecchymoses, facial erythema, increased sweating, subcutaneous fat atrophy, purpura, striae, hyperpigmentation of the skin and nails, hirsutism, acneiform eruptions and hives; reactions to skin tests may be suppressed.

Neurological—convulsions, increased intracranial pressure with papilledema (psuedo- tumor cerebri) usually after treatment, vertigo, headache, and severe mental disturbances.

Endocrine—menstrual irregularities; development of the cushingoid state; suppression of growth in children; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress (e.g., trauma, surgery, or illness); decreased carbohydrate tolerance; manifestations of latent diabetes mellitus; and increased requirements for insulin or oral hypoglycemic agents in diabetics.

Ophthalmic—posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos.

Metabolic—hyperglycemia, glycosuria, and negative nitrogen balance due to protein catabolism.

Allergic Reactions—allergic skin rash, maculopapular rash, and urticaria.

Other adverse reactions that may occur following the administration of a corticosteroid are necrotizing angiitis, thrombophlebitis, aggravation or masking of infections, insomnia, syncopal episodes, and anaphylactoid reactions.

To report SUSPECTED ADVERSE REACTIONS, contact Viona Pharmaceuticals Inc. at 1-888-304-5011 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Development of hypertension, edema, hypokalemia, excessive increase in weight, and increase in heart size are signs of overdosage of fludrocortisone acetate. When these are noted, administration of drugs should be discontinued, after which the symptoms will usually subside within several days; subsequent treatment with fludrocortisone acetate should be with a reduced dose. Muscular weakness may develop due to excessive potassium loss and can be treated by administering a potassium supplement. Regular monitoring of blood pressure and serum electrolytes can help to prevent overdosage (see WARNINGS).

Dosage depends on the severity of the disease and the response of the patient. Patients should be continually monitored for signs that indicate dosage adjustment is necessary, such as remission or exacerbations of the disease and stress (surgery, infection, trauma) (see WARNINGS and PRECAUTIONS, General).

Fludrocortisone Acetate Tablets, USP 0.1 mg — Each white to off-white, round, biconvex, uncoated tablet debossed with '1861' on one side and scored on other side.

They are available as follows:

Bottles of 100 with child resistant-closure:                    NDC 72578-164-01

Bottles of 500:                                                                 NDC 72578-164-05

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Avoid excessive heat.

Dispense in a tightly-closed, light-resistant container (USP).

Manufactured by:

Zydus Lifesciences Ltd.,

Ahmedabad-382210, India

Distributed by:

Viona Pharmaceuticals Inc.

Cranford, NJ 07016

Rev.: 07/24

Fludrocortisone Acetate Tablets, USP 0.1 mg

NDC 72578-164-01 in bottles of 100 tablets with child resistant-closure

Rx only

Viona