Florinef Acetate (Fludrocortisone Acetate Tablets
USP) contains 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-
11ß,17,21-trihydroxypregn-4-ene-3,20-dione 21-acetate; its graphic
Florinef Acetate is available for oral administration as scored tablets
providing 0.1 mg fludrocortisone acetate per tablet. Inactive ingredients:
calcium phosphate, corn starch, lactose, magnesium stearate, sodium
benzoate, and talc.
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
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
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
The approximate plasma half-life
of fludrocortisone (fluorohydrocortisone) is 3.5 hours or more and
the biological half-life is 18 to 36 hours.
Indications and Usage
Florinef Acetate is indicated as partial replacement
therapy for primary and secondary adrenocortical insufficiency in
Addison’s disease and for the treatment of salt-losing adrenogenital
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
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
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.
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
Florinef Acetate (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
Corticosteroids should be used
cautiously in patients with ocular herpes simplex because of possible
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 areused. 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.
be used cautiously in conjunction with corticosteroids in patients
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.
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
(see Drug Interactions).
who are on immunosuppressant doses of corticosteroids should be warned
to avoid exposure to chicken pox or measles and, if exposed, to obtain
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.
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
Inform the patient to keep this medication
and all drugs out of the reach of children.
Patients should be monitored regularly for blood
pressure determinations and serum electrolyte determinations (see WARNINGS).
When administered concurrently, the following drugs
may interact with adrenal corticosteroids.
Amphotericin B or potassium-depleting diuretics (benzothiadiazines and related drugs, ethacrynic acid and furosemide)—enhanced
hypokalemia. Check serum potassium levels at frequent intervals; use
potassium supplements if necessary (see WARNINGS).
Digitalis glycosides—enhanced possibility of arrhythmias or digitalis toxicity
associated with hypokalemia. Monitor serum potassium levels; use potassium
supplements if necessary.
prothrombin time response. Monitor prothrombin levels and adjust anticoagulant
Antidiabetic drugs (oral agents and insulin)—diminished
antidiabetic effect. Monitor for symptoms of hyperglycemia; adjust
dosage of antidiabetic drug upward if necessary.
effect; decreased pharmacologic effect of aspirin. Rarely salicylate
toxicity may occur in patients who discontinue steroids after concurrent
high-dose aspirin therapy. Monitor salicylate levels or the therapeutic
effect for which aspirin is given; adjust salicylate dosage accordingly
if effect is altered (see PRECAUTIONS, General).
phenytoin, or rifampin—increased metabolic clearance
of fludrocortisone acetate because of the induction of hepatic enzymes.
Observe the patient for possible diminished effect of steroid andincrease the steroid dosage accordingly.
Anabolic steroids (particularly C-17
alkylated androgens such as oxymetholone, methandrostenolone, norethandrolone,
and similar compounds)—enhanced tendency toward edema. Use
caution when giving these drugs together, especially in patients with
hepatic or cardiac disease.
and lack of antibody response (see WARNINGS).
levels of corticosteroid-binding globulin, thereby increasing the
bound (inactive) fraction; this effect is at least balanced by decreased
metabolism of corticosteroids. When estrogen therapy is initiated,
a reduction in corticosteroid dosage may be required, and increased
amounts may be required when estrogen is terminated.
Drug/Laboratory Test Interactions
Corticosteroids may affect the nitrobluetetrazolium
test for bacterial infection and produce false-negative results.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Adequate studies have not been performed in animals
to determine whether fludrocortisone acetate has carcinogenic or mutagenic
activity or whether it affects fertility in males or females.
Adequate animal reproduction studies have not been
conducted with fludrocortisone acetate. However, many corticosteroids
have been shown to be teratogenic in laboratory animals at low doses.
Teratogenicity of these agents in man has not been demonstrated. It
is not known whether fludrocortisone acetate can cause fetal harm
when administered to a pregnant woman or can affect reproduction capacity.
Fludrocortisone acetate should be given to a pregnant woman only if
Infants born of mothers who have received substantial
doses of fludrocortisone acetate during pregnancy should be carefully
observed for signs of hypoadrenalism.
treatment with corticosteroids should be carefully documented in the
infant’s medical records to assist in follow up.
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.
Safety and effectiveness in children have not been
Growth and development of infants
and children on prolonged corticosteroid therapy should be carefully
Elderly subjects may commonly have conditions that
may be exacerbated by fludrocortisone therapy including, but not limited
to, hypertension, edema, hypokalemia, congestive heart failure, cataracts,
glaucoma, increased intraocular pressure, renal insufficiency, and
osteoporisis (see WARNINGS, PRECAUTIONS and ADVERSE REACTIONS). Elderly subjects may also commonly be taking concomitant
drug therapy such as digitalis glycosides, oral anticoagulants, antidiabetic
drugs (oral agents and insulin), and aspirin which may interact with
fludrocortisone (see PRECAUTIONS-Drug Interactions).
In general, dose selection for
an elderly patient should be cautious, usually starting at the low
end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or
other drug therapy.
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.
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.
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.
increased intracranial pressure with papilledema (pseudotumor cerebri)
usually after treatment, vertigo, headache, and severe mental disturbances.
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.
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
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 the drug 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 and Administration
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)
(see WARNINGS and PRECAUTIONS, General).
In Addison’s disease, the combination of Florinef
Acetate (Fludrocortisone Acetate Tablets USP) with a glucocorticoid
such as hydrocortisone or cortisone provides substitution therapy
approximating normal adrenal activity with minimal risks of unwanted
The usual dose is 0.1 mg of Florinef
Acetate 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. Florinef Acetate is 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 Florinef Acetate daily.