INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo FLORINEF TABLETS

SCHEDULING STATUS
S4

PROPRIETARY NAME
(and dosage form)

FLORINEF TABLETS

COMPOSITION
A tablet containing 0,1 mg
fludrocortisone acetate, the 9-alpha-fluoro derivative of hydrocortisone.

PHARMACOLOGICAL CLASSIFICATION
Category A 21.5.1. Corticosteroids and analogues.

PHARMACOLOGICAL ACTION
Although the physiological action of fludrocortisone is similar in kind to that of hydrocortisone, its effects, particularly on electrolyte balance, and also on carbohydrate metabolism are considerably heightened and prolonged.
Since fludrocortisone acetate exerts so profound a mineralocorticoid effect, its usefulness is limited to clinical applications which utilise this effect, and it should not be used as an anti-inflammatory agent for the treatment of such cortisone-responsive diseases as rheumatoid arthritis, certain allergies and dermatoses.
Small oral doses of fludrocortisone acetate produce marked sodium retention and increased urinary potassium excretion. Fludrocortisone acetate also causes a rise in blood pressure, apparently because of these effects on electrolyte levels. In larger doses, the steroid inhibits endogenous adrenal cortical secretion, thymic activity, and pituitary corticotrophin secretion; promotes the deposition of liver glycogen; and, unless protein intake is adequate, induces negative nitrogen balance.
The approximate half-life of fludrocortisone is 18 to 36 hours. It is highly protein bound and is eliminated by the kidneys, mostly as inactive metabolites. Duration of action is 1 to 2 days.

INDICATIONS
In frank adrenal insufficiency, such as Addison’s disease, the combination of fludrocortisone acetate with a glucocorticoid such as hydrocortisone or cortisone provides substitution therapy approximating normal adrenal activity with minimal risks of unwanted effects. To achieve the same optimal electrolyte and gluconeogenic effects with a glucocorticoid alone would require the use of doses high enough to produce serious undesirable steroid effects; by combining both types of steroid, the dosage of each may be reduced to well below hazardous levels.

CONTRA-INDICATIONS
Those conditions which are usually considered absolute contraindications to the use of corticosteroids are tuberculosis, acute psychosis, and ocular herpes simplex; relative contra-indications include active peptic ulcer, acute glomerulonephritis, fungal diseases, vaccinia, and varicella. When fludrocortisone acetate is indicated in the presence of any of these conditions, the need for the steroid must be thoroughly weighed against its possible harm.
FLORINEF is contra-indicated in patients with suspected or known hypersensitivity to fludrocortisone or any of the inactive ingredients.
FLORINEF should not be used in patients with uncontrolled congestive heart failure.
Use in pregnancy and nursing
Many corticosteroids have been shown to be teratogenic in laboratory animals at low doses.
Since adequate human reproduction studies have not been done with corticosteroids, the use of fludrocortisone in pregnancy, nursing mothers, or women of child-bearing potential is not recommended.

WARNINGS
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.
Fludrocortisone increases calcium excretion, which may predispose to osteoporosis or aggravate preexisting osteoporosis.
Fludrocortisone may mask some signs of infection, and new infections may appear during its use. There may be decreased resistance and inability to localize infection when fludrocortisone is used. Chicken pox, measles, herpes zoster, or threadworm infestations, for example, can have a more serious or even fatal course in non-immune children or adults on fludrocortisone.
Patients should not be vaccinated or immunized while on fludrocortisone therapy, especially on high doses, because of a lack of antibody response predisposing to medical complications, particularly neurological ones.
The use of fludrocortisone acetate tablets in patients with active tuberculosis should be restricted to cases on fulminating or disseminated tuberculosis in which fludrocortisone is used for the management of the disease in conjunction with an appropriate antituberculous regimen.
Chemoprophylaxis should be used in patients with latent tuberculosis or tuberculin reactivity who are taking fludrocortisone.
Prolonged use of fludrocortisone may produce posterior subcapsular cataracts or glaucoma, with possible damage to the optic nerve. Prolonged use may also enhance the likelihood of secondary ocular infections.

DOSAGE AND DIRECTIONS FOR USE
Addison’s Disease
The usual dose is 0,1 mg daily, although dosage ranging from 0,1 mg 3 times a week to 0,2 mg daily has been employed. In hypertensive patients the recommended dose is 0,05 mg daily. Fludrocortisone acetate is preferably administered in conjunction with cortisone (6,25 mg to 25 mg daily in divided doses) or hydrocortisone (5 mg to 20 mg daily in divided doses).
Dosage depends on the severity of the disease and the response of the patient. The lowest possible dose should be used to control the condition being treated and a reduction in dosage should be made (gradually) when possible.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
Side effects include Cushingoid changes such as facial rounding, buffalo hump or other signs of fat deposition; subcutaneous fat atrophy; weakness or wasting of skeletal muscle; osteoporosis; spontaneous fractures; aseptic necrosis of the hip; necrotising angiitis; bruising or purpura; thrombophlebitis; masking of infections; activation or aggravation of peptic ulcer or other, more minor gastrointestinal difficulties; activation of latent diabetes or aggravation of existing diabetes; menstrual disturbances; hirsutism; acneiform eruptions; vertigo; headache; or severe mental disturbances. Increased intracranial pressure, increased intraocular pressure, papilloedema, and posterior subcapsular cataracts have also been reported with corticosteroid administration. Anorexia, convulsions, diarrhoea, myasthenia, overdose, syncope, taste perversion and hallucinations have been reported.
Since fludrocortisone acetate is a potent mineralocorticoid, most adverse reactions to FLORINEF are caused by this activity and include hypertension, oedema, cardiac enlargement, congestive heart failure, potassium loss and hypokalaemic alkalosis.
Both the dosage and the salt intake should therefore 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; supplemental potassium chloride administration may be needed.
Adverse reactions to fludrocortisone may be produced by too rapid withdrawal or by continued use of large doses.
To avoid 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.
The use of steroids during pregnancy, particularly the first trimester, calls for extreme caution, and infants whose mothers have been receiving fludrocortisone acetate should be examined carefully at birth for signs of hypoadrenalism. The growth suppressing effects of steroids should be borne in mind when they are administered to the paediatric age group.
The anti-inflammatory effect of corticosteroids may mask symptoms of infection and permit the spread of an invading organism. If an infection occurs during fludrocortisone acetate therapy, it should be promptly controlled by suitable antimicrobial therapy.
There is an enhanced corticosteroid effect in patients with hypothyroidism and in those with cirrhosis.
Fludrocortisone should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation.
Psychiatric disturbances may appear with fludrocortisone use. These can include insomnia, depression (sometimes severe) euphoria, mood swings, psychotic symptoms and personality changes. Preexisting emotional instability or psychosis may also be aggravated by fludrocortisone. The use of antidepressant medication does not relieve and may exacerbate andrenocorticoid-induced mental disturbances.
Fludrocortisone should be used with caution in patients with the following conditions: nonspecific ulcerative colitis (if there is a probability of perforation, abscess, or other pyogenic infection); diverticulitis; recent intestinal anastomoses; active or latent peptic ulcer, renal insufficiency; acute glomulonephritis, chronic nephritis, hypertension; congestive heart failure; thrombophlebitis; thromboembolism; osteoporosis; exanthema; Cushing's syndrome; diabetes mellitus; convulsive disorders; metastatic carcinoma; and myasthenia gravis. Further, corticosteroid therapy has caused menstrual irregularities and hyperacidity or peptic ulcer. An adequate protein intake is advised for patients on long-term use to counteract any tendency to weight loss or muscle wasting/weakness associated with negative nitrogen balance.
INTERACTIONS
When administered concurrently, the following medicines may interact with adrenal corticosteroids:
Amphotericin B or potassium-depleting diuretics: (benzothiadiazines and related medicines, ethacrynic acid and furosemide): Enhanced hypokalemia. Potassium levels should be checked at frequent intervals and potassium supplements used if necessary (see WARNINGS).
Anticholinesterases: Effects of the anticholinesterase agent may be antagonized.
Anticoagulants, oral: Corticosteroids may potentiate or decrease anticoagulant action. Patients receiving oral anticoagulants and corticosteroids should therefore be closely monitored.
Antidiabetics (oral agents and insulin): Diminished antidiabetic effect. Patient should be monitored for symptoms of hyperglycemia; dosage of antidiabetic medication should be adjusted if necessary.
Antitubercular medicine: Isoniazid serum concentrations may be decreased in some patients.
Cyclosporine: Increased activity of both cyclosporine and fludrocortisone may occur when the two are used concurrently.
Digitalis glycosides: Enhanced possibility of arrhythmias or digitalis toxicity associated with hypokalemia. Potassium levels should be monitored and potassium supplements used if necessary.
Estrogens, including oral contraceptives: Fludrocortisone half-life and concentration may be increased and clearance decreased. A reduction in fludrocortisone dosage may be required when estrogen therapy is initiated, and an increase required when estrogen is stopped.
Hepatic Enzyme Inducers (eg, barbiturates, phenytoin, carbamazepine, rifampin): Increased metabolic clearance of fludrocortisone. Patients should be observed for possible diminished effect of steroid, and the dosage of FLORINEF should be adjusted accordingly.
Human growth hormone (eg somatrem): The growth promoting effect of somatrem may be inhibited.
Ketoconazole: Fludrocortisone clearance may be decreased, resulting in increased therapeutic effect.
Nondepolarising muscle relaxants: Fludrocortisone may decrease or enhance the neuromuscular blocking action.
Nonsteroidal anti-inflammatory agents (NSAIDs): Increase ulcerogenic effect; decreased pharmacologic effect of aspirin. Conversely, salicylate toxicity may occur in patients who discontinue steroids with concurrent high-dose aspirin therapy. Fludrocortisone should be used cautiously in conjunction with aspirin in patients with hypoprothrombinemia.
Thyroid medicine: Metabolic clearance of fludrocortisone is decreased in hypothyroid patients and increased in hyperthyroid patients . Changes in thyroid status of the patient may necessitate adjustment in fludrocortisone dosage.
Vaccines: Neurological complications and lack of antibody response may occur when patients taking fludrocortisone are vaccinated (see WARNINGS).
LABORATORY TEST INTERACTIONS
Fludrocortisone may affect the nitroblue tetrazolium test for bacterial infection, producing false-negative results.
PAEDIATRIC USE
Because corticosteroids can suppress growth, the growth and development of infants, children and adolescents on prolonged corticosteroid therapy should be carefully monitored. Caution should be used in the event of chicken pox, measles or other communicable diseases. Children should not be vaccinated while on therapy with FLORINEF (see WARNINGS). Corticosteroids may also affect endogenous steroid production.
GERIATRIC USE
The adverse effects of systemic corticosteroids, such as osteoporosis or hypertension, may be associated with more serious consequences in the elderly. Close clinical supervision is therefore recommended.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Treatment of overdosage should be symptomatic and supportive.
Chronic overdosage:
Development of hypertension, oedema, hypokalemia, significant increase in weight, and increase in heart size may be signs of excessive dosage of FLORINEF. When these are noted, administration of FLORINEF should be discontinued, after which the symptoms will usually subside within several days; subsequent treatment with FLORINEF, if necessary, should be resumed at a reduced dose. Muscle weakness due to excessive potassium loss may develop and can be treated with potassium supplements. Monitoring of blood pressure and serum electrolytes can reduce the likelihood of consequences of excessive dosage (see WARNINGS).
Acute overdosage:
For large, acute overdoses, treatment includes gastric lavage or emesis and usual supportive measures.

IDENTIFICATION
FLORINEF are pink, flat faced, bevel edged tablets, 6,3 mm in diameter, bisected on one face and with the word ‘SQUIBB’and the number ‘429’on the opposite face.

PRESENTATION
Bottles of 100 tablets.

STORAGE INSTRUCTIONS
Store at room temperature not exceeding 25°C. Avoid excessive heat.
KEEP OUT OF REACH OF CHILDREN.

REFERENCE NUMBER
G 3134 (Act 101 of 1965).

APPLICANT/ADDRESS
BRISTOL-MYERS SQUIBB (PTY) LIMITED.
47 Van Buuren Road,
Bedfordview 2008.

DATE OF PUBLICATION OF THIS PACKAGE INSERT
November 1996

* Authorised user of the TM FLORINEF.

Updated on this site: June 2005
Source: Pharmaceutical Industry

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