Deltasone®
brand
of prednisone tablets, USP
DESCRIPTION
ACTIONS
INDICATIONS
CONTRAINDICATIONS
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
DOSAGE AND
ADMINISTRATION
HOW SUPPLIED
DESCRIPTION
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.
ACTIONS
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.
INDICATIONS
DELTASONE
Tablets are indicated in the following conditions:
1. 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
2. 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
3. Collagen
Diseases
During an exacerbation or as maintenance therapy in selected cases of: Systemic
lupus erythematosus
Systemic-dermatomyositis (polymyositis)
Acute rheumatic carditis
4. Dermatologic
Diseases
Pemphigus
Bullous dermatitis herpetiformis
Severe erythema multiforme (Stevens-Johnson syndrome)Exfoliative dermatitis
Mycosis fungoides
Severe psoriasis
Severe seborrheic dermatitis
5. Allergic
States
Control of severe or incapacitating allergic conditions intractable to adequate
trials of conventional treatment:
6. Seasonal or perennial allergic
rhinitis
Bronchial asthma
Contact dermatitis
Atopic dermatitis
Serum sickness
Drug hypersensitivity reactions
7. Ophthalmic
Diseases
Severe acute and chronic allergic and inflammatory processes involving the eye
and its adnexa such as:
8. 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
9. 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
10. Aspiration pneumonitis
11. Hematologic
Disorders
Idiopathic thrombocytopenic purpura in adults
Secondary thrombocytopenia in adults
Acquired (autoimmune) hemolytic anemia
Erythroblastopenia (RBC anemia)
Congenital (erythroid) hypoplastic anemia
12. Neoplastic
Diseases
For palliative management of:
Leukemias and lymphomas in adults
Acute leukemia of childhood
13. 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
14. Gastrointestinal
Diseases
To tide the patient over a critical period of the disease in:
Ulcerative colitis
Regional enteritis
15. Nervous
System
Acute exacerbations of multiple sclerosis
16. Miscellaneous
Tuberculous meningitis with subarachnoid block or impending block when used
concurrently with appropriate antituberculous chemotherapy Trichinosis with neurologic or myocardial involvement
CONTRAINDICATIONS
Systemic fungal infections and known
hypersensitivity to components.
WARNINGS
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.
PRECAUTIONS
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.
ADVERSE REACTIONS
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
DOSAGE AND ADMINISTRATION
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:
1. Basic principles and indications
for corticosteroid therapy should apply. The benefits of ADT should not
encourage the indiscriminate use of steroids.
2. ADT is a therapeutic technique
primarily designed for patients in whom long-term pharmacologic corticoid
therapy is anticipated.
3. 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.
4. 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.
5. 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).
6. 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).
7. 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.
8. 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.
9. 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.
HOW SUPPLIED
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 0009-0032-015 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 0009-0045-0510 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 0009-0193-0320 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 0009-0165-0350 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