For the use of a Registered Medical Practitioner or a Hospital or a Institution only.
FLUDROCORTISONE ACETATE TABLETS USP (Fludrocortisone Acetate) is a synthetic adrenocortical steroid possessing very potent mineralocorticoid properties and high glucocorticoid activity; it is used only for its mineralocorticoid effects. Chemically, Fludrocortisone
Acetate is Pregn-4-ene-3, 20-dione, 21-(acetyloxy)-9-fluoro-11, 17-dihydroxy-, (11β)- 9-Fluoro-11β, 17,21-trihydroxypregn-4-ene-3,20-dione 21-acetate. The molecular formula is C23H31FO6 and molecular weight is 422.50.
STRUCTURAL FORMULA :
Its structural formula is :
FLUDROCORTISONE ACETATE TABLETS USP are white coloured, circular, biconvex tablets having score line on one side and “SGP” embossed on other side of each tablet.
Each uncoated tablet contains :
Fludrocortisone Acetate USP 0.1 mg
Fludrocortisone acetate is an adrenal cortical steroid that has very high levels of mineralocorticoid activity and moderate levels of glucocorticoid activity. However, it is used only for its mineralocorticoid effects. Mineralocorticoids act on the distal tubules to increase potassium excretion, hydrogen ion excretion, and sodium reabsorption and subsequent water retention. Cation transport in other secretory cells is similarly affected; excretion of water and electrolytes by the large intestine and by salivary and sweat glands is also altered, but to a lesser extent. At the cellular level, corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of mRNA (messenger RNA) and subsequent protein synthesis of various enzymes thought to be ultimately responsible for the physiological effects of these hormones.
Fludrocortisone is readily absorbed from the gastrointestinal tract. The plasma half-life is about 3.5 hours or more, but fludrocortisone exhibits a more prolonged biological half-life of 18 to 36 hours.
FLUDROCORTISONE ACETATE TABLETS USP 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.
FOR ORAL USE.
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 remissions or exacerbations of the disease and stress (surgery, infection, trauma).
Addison’s Disease :
In Addison’s disease, the combination of FLUDROCORTISONE ACETATE TABLETS USP with a glucocorticoid such as hydrocortisone or cortisone provides substitution therapy approximating normal adrenal activity with minimal risks of unwanted effects. The usual dose is 0.1 mg of FLUDROCORTISONE ACETATE TABLETS USP daily, although dosage ranging from 0.1 mg three times a week to 0.2 mg daily has been employed. In the event transient hypertension develops as a consequence of therapy, the dose should be reduced to 0.05 mg daily. FLUDROCORTISONE ACETATE TABLETS USP are preferably administered in conjunction with cortisone (10 mg to 37.5 mg daily in divided doses) or hydrocortisone (10 mg to 30 mg daily in divided doses).
Salt-Losing Adrenogenital Syndrome :
The recommended dosage for treating the salt-losing adrenogenital syndrome is 0.1 mg to 0.2 mg of FLUDROCORTISONE ACETATE TABLETS USP daily.
Corticosteroids are contraindicated in patients with systemic fungal infections and in those with a history of possible or known hypersensitivity to these agents. FLUDROCORTISONE ACETATE TABLETS USP contains lactose which is contra-indicated in patients with galactosaemia, the glucose-galactose malabsorption syndrome, or lactase deficiency.
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 subcapsular 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, oedema, 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 TABLETS USP 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 varicella 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.
Adverse reactions to corticosteroids may be produced by too rapid withdrawal or by continued use of large doses. To avoid drug-induced adrenal insufficiency, supportive dosage may be required in times of stress (such as trauma, surgery, or severe illness) both during treatment with fludrocortisone acetate and for a year afterwards. There is an enhanced corticosteroid effect in patients with hypothyroidism and in those with cirrhosis. Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation. The lowest possible dose of corticosteroid should be used to control the condition being treated. A gradual reduction in dosage should be made when possible. Psychic derangements may appear when corticosteroids are used. These may range from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Existing emotional instability or psychotic tendencies may also be aggravated by corticosteroids.
Aspirin should be used cautiously in conjunction with corticosteroids in patients with hypoprothrombinaemia. Corticosteroids should be used with caution in patients with nonspecific ulcerative colitis if there is a probability of impending perforation, abscess, or other pyogenic infection. Corticosteroids should also be used cautiously in patients with diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis. FLUDROCORTISONE ACETATE TABLETS USP should be used cautiously in diabetic patients.
Pregnancy : Category C
Studies on use of fludrocortisone during pregnancy have not been done in humans. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be closely observed for signs of hypoadrenalism. Studies on use of fludrocortisone during pregnancy have not been done in animals.
Nursing Mothers :
Corticosteroids are found in the breast milk of lactating women receiving systemic therapy with these agents. Caution should be exercised when fludrocortisone acetate is administered to a nursing woman.
Paediatric Use :
Safety and effectiveness in children have not been established. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed.
INTERACTIONS AND INCOMPATIBILITIES :
Amphotericin B injection and potassium-depleting agents : Patients should be observed for hypokalemia. Anticholinesterases : Effects of anticholinesterase agents may be antogonised. Anticoagulants, oral : Corticosteroids may potentiate or decrease anticoagulant action. Patients receiving oral anticoagulants and corticosteroids should therefore be closely monitored.
Antidiabetics : Corticosteroids may increase blood glucose; diabetic control should be monitored, especially when corticosteroids are initiated, discontinued, or changed in dosage.
Antihypertensives, including diuretics : corticosteroids antagonise the effects of antihypertensives and diuretics. The hypokalaemic effect of diuretics, including acetazolamide, is enhanced.
Anti-tubercular drugs : Isoniazid serum concentrations may be decreased.
Cyclosporin : Monitor for evidence of increased toxicity of cyclosporin when the two are used concurrently.
Digitalis glycosides : Co-administration may enhance the possibility of digitalis toxicity.
Oestrogens, include oral contraceptives : Corticosteroid half-life and concentration may be increased and clearance decreased. Hepatic Enzyme Inducers (e.g. aminoglutethemide, barbiturates, carbamazepine, phenytoin, primidone,
rifabutin, rifampicin) : There may be increased metabolic clearance of Florinef. Patients should be carefully observed for possible diminished effect of steroid, and the dosage should be adjusted accordingly.
Human growth hormone : The growth-promoting effect may be inhibited.
Ketoconazole : Corticosteroid clearance may be decreased, resulting in increased effects.
Nondepolarising muscle relaxants : Corticosteroids may decrease or enhance the neuromuscular blocking action.
Nonsteroidal anti-inflammatory agents (NSAIDS) : Corticosteroids may increase the incidence and/or severity of GI bleeding and ulceration associated with NSAIDS. Also, corticosteroids can reduce serum salicylate levels and therefore decrease their effectiveness. Conversely, discontinuing corticosteroids during high-dose salicylate therapy may result in salicylate toxicity. Aspirin should be used cautiously in conjunction with corticosteroids in patients with hypoprothrombinaemia.
Thyroid drugs : Metabolic clearance of adrenocorticoids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in adrenocorticoid dosage.
Vaccines : Neurological complications and lack of antibody response may occur when patients taking corticosteroids are vaccinated.
Drug/Laboratory Test Interactions : Corticosteroids may affect the nitrobluetetrazolium test for bacterial infection and produce false – negative results
EFFECTS ON ABILITY TO DRIVE AND USE
SIDE EFFECTS :
Where adverse reactions occur they are usually reversible on cessation of therapy. The incidence of predictable side-effects, including hypothalamic-pituitary-adrenal suppression correlate with the relative potency of the drug, dosage, timing of administration and duration of treatment. Patients should be watched closely for the following adverse reactions which may be associated with any
corticosteroid therapy :
Anti-inflammatory and immunosuppressive effects :
Increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections, recurrence of dormant tuberculosis. Fluid and electrolyte disturbances : sodium retention, fluid retention, congestive heart failure in susceptible patients, potassium loss, cardiac arrhythmias or ECG changes due to potassium deficiency, hypokalaemic alkalosis, increased calcium excretion and hypertension. Musculoskeletal : muscle weakness, fatigue, steroid myopathy, loss of muscle mass, osteoporosis,
avascular osteonecrosis, vertebral compression fractures, delayed healing of fractures, aseptic necrosis of femoral and humeral heads, pathological fractures of long bones and spontaneous fractures, tendon rupture.
Gastrointestinal : dyspepsia, peptic ulcer with possible subsequent perforation and haemorrhage, pancreatitis, abdominal distension and ulcerative oesophagitis, candidiasis. Hypersensitivity : Anaphylatic reactions, angiodema, rash, pruritus and urticaria, particularly where there is a history of drug allergies.
Dermatologic : impaired wound healing, thin fragile skin, petechiae and ecchymoses, facial erythema, increased sweating, purpura, striae, hirsutism, acneiform eruptions, lupus erythematosus-like lesions and suppressed reactions to skin tests.
Neurological : euphoria, psychological dependence, depression, insomnia, convulsions, increased intracranial pressure with papilloedema (pseudo-tumour cerebri) usually after treatment, vertigo, headache, neuritis or paraesthesias and aggravation of pre-existing psychiatric conditions and epilepsy. A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood, and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations, and aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported. Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to be 5 - 6 %. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown.
Endocrine/metabolic : menstrual irregularities and amenorrhoea; development of the Cushingoid state; suppression of growth in childhood and adolescence; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress (eg. trauma, surgery or
illness); decreased carbohydrate tolerance; manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycaemic agents in diabetes, weight gain. Negative protein and calcium balance. Increased appetite. Ophthalmic : posterior subcapsular cataracts, increased intraocular pressure, glaucoma, exophthalmos, papilloedema, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal diseases.
Others : necrotising angiitis, thrombophlebitis, thromboembolism, leucocytosis, insomnia and syncopal episodes.
Withdrawal Symptoms and Signs : On withdrawal, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and weight loss may occur. Too rapid a reduction in dose following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death.
INFORMATION FOR PATIENTS :
The physician should advise the patient to report any medical history of heart disease, high blood pressure, or kidney or liver disease and to report current use of any medicines to determine if these medicines might interact adversely with FLUDROCORTISONE ACETATE TABLETS USP. Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chicken pox or measles and, if exposed, to obtain medical advice.The patient’s understanding of his steroid-dependent status and increased dosage requirement under widely variable conditions of stress is vital. Advise the patient to carry medical identification indicating his dependence on steroid medication and, if necessary, instruct him to carry an adequate supply of medication for use in emergencies. Stress to the patient the importance of regular follow-up visits to check his progress and the need to promptly notify the physician of dizziness, severe or continuing headaches, swelling of feet or lower legs, or unusual weight gain. Advise the patient to use the medicine only as directed, to take a missed dose as soon as possible, unless it is almost time for the next dose, and not to double the next dose. Inform the patient to keep this medication and all drugs out of the reach of children.
Development of hypertension, oedema, hypokalaemia, excessive increase in weight, and increase in heart size are signs of overdosage of FLUDROCORTISONE ACETATE TABLETS USP. When these are noted, administration of the drug should be discontinued, after which the symptoms will usually subside within several days.
TREATMENT OF OVERDOSAGE :
A single large dose should be treated with plenty of water by mouth. Careful monitoring of serum electrolytes is essential, with particular consideration being given to the need for administration of potassium chloride and restriction of dietary sodium intake.
Store below 30°C (86°F), protected from moisture and light.
Do not refrigerate.
SHELF LIFE :
24 months from the date of manufacture.
FLUDROCORTISONE ACETATE TABLETS USP contains Fludrocortisone Acetate 0.1 mg.
10 blisters of 10 tablets per box.
Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.