DELTASONE Tablets contain prednisone which is a glucocorticoid. Glucocorticoids are adrenocortical
steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract.
Prednisone is a white to practically white, odorless, crystalline powder. It is very slightly soluble in water; slightly
soluble in alcohol, in chloroform, in dioxane, and in methanol.
The chemical name for prednisone is pregna-1,4-diene-3,11,20-trione, 17,21-dihydroxy- and its molecular weight
is 358.43.
The structural formula is represented below:
DELTASONE Tablets are available in 5 strengths: 2.5 mg, 5 mg, 10 mg, 20 mg and 50 mg. Inactive ingredients: 2.5 mg-Calcium Stearate, Corn Starch, Erythrosine Sodium, Lactose, Mineral Oil, Sorbic Acid and Sucrose. 5 mg- Calcium Stearate, Corn Starch, Lactose, Mineral Oil, Sorbic Acid and Sucrose. 10 mg-Calcium Stearate, Corn Starch, Lactose, Sorbic Acid and Sucrose. 20 mg-Calcium Stearate, Corn Starch, FD&C Yellow No. 6, Lactose, Sorbic Acid and Sucrose. 50 mg-Corn Starch, Lactose, Magnesium Stearate, Sorbic Acid, Sucrose, and Talc.
Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties,
are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used
for their potent anti-inflammatory effects in disorders of many organ systems.
Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune
responses to diverse stimuli.
DELTASONE Tablets are indicated in the following conditions:
Systemic fungal infections and known hypersensitivity to components.
In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting
corticosteroids before, during, and after the stressful situation is indicated.
Corticosteroids may mask some signs of infection, and new infections may appear during their use. Infections
with any pathogen including viral, bacterial, fungal, protozoan or helminthic infections, in any location of the
body, may be associated with the use of corticosteroids alone or in combination With other immunosuppressive
agents that affect cellular immunity, humoral immunity, or neutrophil function.1
These infections may be mild, but can be severe and at times fatal. With increasing doses of corticosteroids, the
rate of occurrence of infectious complications increases.2 There may be decreased resistance and inability to localize infection when corticosteroids are used.
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.
Usage in pregnancy: Since adequate human reproduction studies have not been done with corticosteroids, the
use of these drugs in pregnancy, nursing mothers or women of childbearing potential requires that the possible
benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of
mothers who have received substantial doses of corticosteroids during pregnancy, should be carefully observed
for signs of hypoadrenalism.
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. Dietary salt restriction and potassium supplementation may be
necessary. All corticosteroids Increase calcium excretion.
Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive
doses of corticosteroids. Killed or inactivated vaccines may be administered to patients receiving
immunosuppressive doses of corticosteroids; however, the response to such vaccines may be diminished.
Indicated immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of
corticosteroids.
The use of DELTASONE Tablets in 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 anti-tuberculous regimen.
If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is
necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients
should receive chemoprophylaxis.
Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy
individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in non-immune
children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care
should be taken to avoid exposure. How the dose, route and duration of corticosteroid administration affects the
risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior
corticosteroid treatment to the risk is also not known. If exposed to chicken pox, prophylaxis with varicella
zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular
immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG
prescribing information.) If chicken pox develops, treatment with antiviral agents may be considered. Similarly,
corticosteroids. should be used with great care in patients with known or suspected Strongyloides (threadworm)
infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides
hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis
and potentially fatal gram-negative septicemia.
General Precautions
Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This
type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of
stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion
may be impaired, salt and/or a mineralocorticoid should, be administered concurrently.
There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis.
Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible cornmeal
perforation.
The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when
reduction in dosage is possible, the reduction should be gradual.
Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood
swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional
instability or psychotic tendencies may be aggravated by corticosteroids.
Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending
perforation, abscess or other pyogenic infection; diverticulitis; fresh intestinal anastomoses; active or latent peptic
ulcer; renal insufficiency; hypertension; osteoporosis; and myasthenia gravis.
Growth and development of infants and children on prolonged corticosteroid therapy should be carefully
observed.
Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of
corticosteroids may result in clinical remission.
Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute
exacerbations of multiple sclerosis, they do not show that corticosteroids affect the ultimate outcome or natural
history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to
demonstrate a significant effect. (See DOSAGE AND ADMINISTRATION.)
Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of
treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and
as to whether daily or intermittent therapy should be used.
Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin. Since concurrent
use of these agents results in a mutual inhibition of metabolism, it is possible that adverse events associated with
the individual use of either drug may be more apt to occur.
Drug Interactions
The pharmacokinetic interactions listed below are potentially clinically important. Drugs that induce hepatic
enzymes such as phenobarbital, phenytoin and rifampin may increase the clearance of corticosteroids and may
require increases in corticosteroid dose to achieve the desired response. Drugs such as troleandomycin and
ketoconazole may inhibit the metabolism of corticosteroids and thus decrease their clearance. Therefore, the
dose of corticosteroid should be titrated to avoid steroid toxicity. Corticosteroids may increase the clearance of
chronic high dose aspirin. This could lead to decreased salicylate serum levels or increase the risk of salicylate
toxicity when corticosteroid is withdrawn. Aspirin should be used cautiously in conjunction with corticosteroids
in patients suffering from hypoprothrombinemia. The effect of corticosteroids on oral anticoagulants is variable.
There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with
corticosteroids.
Therefore, coagulation indices should be monitored to maintain the desired anticoagulant effect.
Information for the Patient
Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to
chicken pox or measles. Patients should also be advised that if they are exposed, medical advice should be
sought without delay.
Fluid and Electrolyte Disturbances
The initial dosage of DELTASONE Tablets may vary from 5 mg to 60 mg of prednisone per day depending on the specific disease entity being treated. In situations of less severity lower doses will generally suffice while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, DELTASONE should be discontinued and the patient transferred to other appropriate therapy. IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation it may be necessary to increase the dosage of DELTASONE for a period of time consistent with the patient's condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
Multiple Sclerosis
In the treatment of acute exacerbations of multiple sclerosis daily doses of 200 mg of prednisolone for a week
followed by 80 mg every other day for 1 month have been shown to be effective. (Dosage range is the same for
prednisone and prednisolone.)
ADT® (Alternate Day Therapy)
ADT is a corticosteroid dosing regimen in which twice the usual daily dose of corticoid is administered every
other morning. The purpose of this mode of therapy is to provide the patient requiring long-term pharmacologic
dose treatment with the beneficial effects of corticoids while minimizing certain undesirable effects, including
pituitary-adrenal suppression, the Cushingoid state, corticoid withdrawal symptoms, and growth suppression in
children.
The rationale for this treatment schedule is based on two major premises: (a) the anti-inflammatory or
therapeutic effect of corticoids persists longer than their physical presence and metabolic effects and (b)
administration of the corticosteroid every other morning allows for re-establishment of more nearly normal
hypothalamic-pituitary-adrenal (HPA) activity on the off-steroid day.
A brief review of the HPA physiology may be helpful in understanding this rationale. Acting primarily through
the hypothalamus a fall in free cortisol stimulates the pituitary gland to produce increasing amounts of
corticotropin (ACTH) while a rise in free cortisol inhibits ACTH secretion. Normally the HPA system is
characterized by diurnal (circadian) rhythm. Serum levels of ACTH rise from a low point about 10 pm to a peak
level about 6 am. Increasing levels of ACTH stimulate adrenocortical activity resulting in a rise in plasma
cortisol with maximal levels occurring between 2 am and 8 am. This rise in cortisol dampens ACTH production
and in turn adrenocortical activity. There is a gradual fall in plasma corticoids during the day with lowest levels
occurring abæmidnight.
The diurnal rhythm of the HPA axis is lost in Cushing's disease, a syndrome of adrenocortical hyperfunction
characterized by obesity with centripetal fat distribution, thinning of the skin with easy bruisability, muscle
wasting with weakness, hypertension, latent diabetes, osteoporosis, electrolyte imbalance, etc. The same clinical
findings of hyperadrenocorticism may be noted during long-term pharmacologic dose corticoid therapy
administered in conventional daily-divided doses. It would appear, then, that a disturbance in the diurnal cycle
with maintenance of elevated corticoid values during the night may play a significant role in the development of
undesirable corticoid effects. Escape from these constantly elevated plasma levels for even short periods of time
may be instrumental in protecting against undesirable pharmacologic effects.
During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent
suppression of cortisol production by the adrenal cortex. Recovery time for normal HPA activity is variable
depending upon the dose and duration of treatment. During this time the patient is vulnerable to any stressful
situation. Although it has been shown that there is considerably less adrenal suppression following a single
morning dose of prednisolone (10 mg) as opposed to a quarter of that dose administered every 6 hours, there is
evidence that some suppressive effect on adrenal activity may be carried over into the following day when
pharmacologic doses are used. Further, it has been shown that a single dose of certain corticosteroids will
produce adrenocortical suppression for two or more days. Other corticoids, including rnethylprednisolone,
hydrocortisone, pednisone and prednisolone, are considered to be short acting (producing adrenocortical
suppression for 1 1/4 to 1 1/2 days following a single dose) and thus are recommended for alternate day therapy.
The following should be kept in mind when considering alternate day therapy:
DELTASONE Tablets are available in the following strengths and package sizes:
2.5 mg (pink, round, scored, imprinted DELTASONE 2.5)
Bottles of 100 NDC 0009-0032-01
5 mg (white, round, scored, imprinted DELTASONE 5)
Bottles of 100 NDC 0009-0045-01
Bottles of 500 NDC 0009-0045-02
Bottles of 1000 NDC 0009-0045-16
DOSEPAK Unit-of-Use (21 tablets)
NDC 0009-0045-04
Unit Dose Packages (100) NDC 0009-0045-05
10 mg (white, round, scored, imprinted DELTASONE 10)
Bottles of 100 NDC 0009-0193-01
Bottles of 500 NDC 0009-0193-02
Unit Dose Packages (100) NDC 0009-0193-03
20 mg (peach, round, scored, imprinted DELTASONE 20)
Bottles of 100 NDC 0009-0165-01
Bottles of 500 NDC 0009-0165-02
Unit Dose Packages (100) NDC 0009-0165-03
50 mg (white, round, scored, imprinted DELTASONE 50)
Bottles of 100 NDC 0009-0388-01
Store at controlled room temperature 15º to 30ºC (59º to 86º F).
REFERENCES
1 Fekety R. Infections associated with corticosteroids and immunosuppressive therapy. In: Gorbach SL,
Bartlett JG, Blacklow NR, eds. Infectious Diseases. Philadelphia: WBSaunders Company 1992:1050-1.
2 Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticoids. Rev Infect Dis 1989:11(6):954-63.
Caution: Federal law prohibits dispensing without prescription.
Revised September 1995
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