tablets, USP
DESCRIPTION
ACTIONS
INDICATIONS
CONTRAINDICATIONS
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION
HOW SUPPLIED
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:
- Endocrine Disorders
Primary or secondary adrenocortical insufficiency- (hydrocortisone or cortisone is the first choice; synthetic
analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid
supplementation is of particular importance)Congenital adrenal hyperplasia
Hypercalcernia associated with cancer
Nonsuppurative thyroiditis - Rheumatic Disorders
As adjunctive therapy for short-term administration- (to tide the patient over an acute episode or exacerbation) in:
Psoriatic arthritis
Rheumatoid arthritis, including juvenile rheumatoid arthritis- (selected cases may require low-dose maintenance
therapy)Ankylosing spondylitis
Acute and subacute bursitis
Acute nonspecific tenosynovitis
Acute gouty arthritis
Post-traumatic osteoarthritis
Synovitis of osteoarthritis
Epicondylitis - Collagen Diseases
During an exacerbation or as maintenance therapy in selected- cases of:
Systemic lupus erythematosus
Systemic-dermatomyositis (polymyositis)
Acute rheumatic carditis - Dermatologic Diseases
Pemphigus
Bullous dermatitis herpetiformis
Severe erythema multiforme- (Stevens-Johnson syndrome)
Exfoliative dermatitis
Mycosis fungoides
Severe psoriasis
Severe seborrheic dermatitis - Allergic States
Control of severe or incapacitating allergic conditions- intractable to adequate trials of conventional treatment:
Seasonal or perennial allergic rhinitis
Bronchial asthma
Contact dermatitis
Atopic dermatitis
Serum sickness
Drug hypersensitivity reactions - Ophthalmic Diseases
Severe acute and chronic allergic and inflammatory processes- involving the eye and its adnexa such as:
Allergic cornea marginal ulcers
Herpes zoster ophthalmicus
Anterior segment inflammation
Diffuse posterior uveitis and choroiditis
Sympathetic ophthalmia
Allergic conjunctivitis
Keratitis
Chorioretinitis
Optic neuritis
Iritis and iridocyclitis - Respiratory Diseases
Symptomatic sarcoidosis
Loeffler’s syndrome not manageable by other means
Berylliosis
Fulminating or disseminated pulmonary tuberculosis when used- concurrently with appropriate antituberculous chemotherapy
Aspiration pneumonitis
- Hematologic Disorders
Idiopathic thrombocytopenic purpura in adults
Secondary thrombocytopenia in adults
Acquired (autoimmune) hemolytic anemia
Erythroblastopenia (RBC anemia)
Congenital (erythroid) hypoplastic anemia - Neoplastic Diseases
For palliative management of:
Leukemias and lymphomas in adults
Acute leukemia of childhood - Edematous States
To induce a diuresis or remission of proteinuria in the- nephrotic syndrome, without uremia, of the idiopathic type
or that due to lupus erythematosus - Gastrointestinal Diseases
To tide the patient over a critical period of the disease in:
Ulcerative colitis
Regional enteritis - Nervous System
Acute exacerbations of multiple sclerosis - Miscellaneous
Tuberculous meningitis with subarachnoid block or impending- block when used concurrently with appropriate antituberculous chemotherapy
Trichinosis with neurologic or myocardial involvement
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
-
Sodium retention
Fluid retention
Congestive heart failure in susceptible patients
Potassium loss
Hypokalemic alkalosis
Hypertension
Musculoskeletal
-
Muscle weakness
Steroid myopathy
Loss of muscle mass
Osteoporosis
Tendon rupture, particularly of the Achilles tendon
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathologic fracture of long bones
Gastrointestinal
-
Peptic ulcer with possible perforation and hemorrhage
Pancreatitis
Abdominal distention
Ulcerative esophagitis
Increases in alanine transaminase (ALT, SGPT), aspartate
- transaminase (AST, SGOT) and alkaline phosphatase
have been observed following corticosteroid treatment. These changes are usually small, not associated with any
clinical syndrome and are reversible upon discontinuation.
Dermatologic
-
Impaired wound healing
Thin fragile skin
Petechiae and ecchymoses
Facial erythema
Increased sweating
May suppress reactions to skin tests
Metabolic
-
Negative nitrogen balance due to protein catabolism
Neurological
Increased intracranial pressure with papilledema
-
(pseudo-tumor cerebri) usually after treatment
Convulsions
Vertigo
Headache
Endocrine
-
Menstrual irregularities
Development of Cushingoid state
Secondary adrenocortical and pituitary unresponsiveness,
- particularly in times of stress, as in trauma, surgery or
illness
Suppression of growth in children
Decreased carbohydrate tolerance
Manifestations of latent diabetes mellitus
Increased requirements for insulin or oral hypoglycemic agents
- in diabetics
Ophthalmic
-
Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Exophthalmos
Additional Reactions
-
Urticaria and other allergic, anaphylactic or hypersensitivity
- reactions
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 about midnight.
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:
- Basic principles and indications for corticosteroid therapy should apply. The benefits of ADT should not
encourage the indiscriminate use of steroids. - ADT is a therapeutic technique primarily designed for patients in whom long-term pharmacologic corticoid
therapy is anticipated. - In less severe disease processes in which corticoid therapy is indicated, it may be possible to initiate
treatment with ADT. More severe disease states usually will require daily divided high dose therapy for initial
control of the disease process. The initial suppressive dose level should be continued until satisfactory clinical
response is obtained, usually four to ten days in the case of many allergic and collagen diseases. It is important
to keep the period of initial suppressive dose as brief as possible particularly when subsequent use of alternate
day therapy is intended.
Once control has been established, two courses are available: (a) change to ADT and then gradually reduce the
amount of corticoid given every other day or (b) following control of the disease process reduce the daily dose of
corticoid to the lowest effective level as rapidly as possible and then change over to an alternate day schedule.
Theoretically, course (a) may be preferable. - Because of the advantages of ADT, it may be desirable to try patients on this form of therapy who have been
on daily corticoids for long periods of time (eg, patients with rheumatoid arthritis). Since these patients may
already have a suppressed HPA axis, establishing them on ADT may be difficult and not always successful.
However, it is recommended that regular attempts be made to change them over. It may be helpful to triple or
even quadruple the daily maintenance dose and administer this every other day rather than just doubling the daily
dose if difficulty is encountered. Once the patient is again controlled, an attempt should be made to reduce this
dose to a minimum. - As indicated above, certain corticosteroids, because of their prolonged suppressive effect on adrenal activity,
are not recommended for alternate day therapy (eg, dexamethasone and betamethasone). - The maximal activity of the adrenal cortex is between 2 am and 8 am, and it is minimal between 4 pm and
midnight. Exogenous corticosteroids suppress adrenocortical activity the least, when given at the time of
maximal activity (am). - In using ADT it is important, as in all therapeutic situations to individualize and tailor the therapy to each
patient. Complete control of symptoms will not be possible in all patients. An explanation of the benefits of
ADT will help the patient to understand and tolerate the possible flare-up in symptoms which may occur in the
latter part of the off-steroid day. Other symptomatic therapy may be added or increased at this time if needed. - In the event of an acute flare-up of the disease process, it may be necessary to return to a full suppressive
daily divided corticoid dose for control. Once control is again established alternate day therapy may be re-
instituted. - Although many of the undesirable features of corticosteroid therapy can be minimized by ADT, as in any
therapeutic situation, the physician must carefully weigh the benefit-risk ratio for each patient in whom corticoid
therapy is being considered.
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.
The Upjohn Company
Kalamazoo, MI 49001, USA
Revised September 1995
810 342 017
691015