Deltasone

PredniSONE 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
   Nonsuppurative thyroiditis
   Hypercalcemia associated with cancer

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:
   Seasonal or perennial allergic rhinitis
   Bronchial asthma
   Contact dermatitis
   Atopic dermatitis
   Serum sickness
   Drug hypersensitivity reactions

6. Ophthalmic Diseases

   Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as:
   Allergic corneal marginal ulcers
   Herpes zoster ophthalmicus
   Anterior segment inflammation
   Diffuse posterior uveitis and choroiditis
   Sympathetic ophthalmia
   Allergic conjunctivitis
   Keratitis
   Chorioretinitis
   Optic neuritis
   Iritis and iridocyclitis

7. Respiratory Diseases

   Symptomatic sarcoidosis
   Loeffler's syndrome not manageable by other means
   Berylliosis
   Aspiration pneumonitis
   Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy

8. Hematologic Disorders

   Idiopathic thrombocytopenic purpura in adults
   Secondary thrombocytopenia in adults
   Acquired (autoimmune) hemolytic anemia
   Erythroblastopenia (RBC anemia)
   Congenital (erythroid) hypoplastic anemia

9. Neoplastic Diseases

   For palliative management of:
   Leukemias and lymphomas in adults
   Acute leukemia of childhood

10. 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

11. Gastrointestinal Diseases

    To tide the patient over a critical period of the disease in:
    Ulcerative colitis
    Regional enteritis

12. Miscellaneous

    Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy
    Trichinosis with neurologic or myocardial involvement

Alternate Day Therapy

Alternate day therapy 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 methylprednisolone, hydrocortisone, prednisone, and prednisolone, are considered to be short acting (producing adrenocortical suppression for 1¼ to 1½ 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 alternate day therapy should not encourage the indiscriminate use of steroids.

2. Alternate day therapy 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 alternate day therapy. 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 alternate day therapy 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 alternate day therapy, it may be desirable to try patients on this form of therapy who have been on daily corticoids for long periods of time (e.g., patients with rheumatoid arthritis). Since these patients may already have a suppressed HPA axis, establishing them on alternate day therapy 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 (e.g., 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 alternate day therapy 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 alternate day therapy 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 alternate day therapy, as in any therapeutic situation, the physician must carefully weigh the benefit-risk ratio for each patient in whom corticoid therapy is being considered.

(listed alphabetically, under each subsection)
The following adverse reactions have been reported with prednisone or other corticosteroids:

Allergic Reactions
anaphylactoid or hypersensitivity reactions, anaphylaxis, angioedema.

Cardiovascular System
bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, ECG changes caused by potassium deficiency, edema, fat embolism, hypertension or aggravation of hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction (see WARNINGS: Cardio-Renal), necrotizing angiitis, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis.

Dermatologic
acne, acneiform eruptions, allergic dermatitis, alopecia, angioedema, angioneurotic edema, atrophy and thinning of skin, dry scaly skin, ecchymoses and petechiae (bruising), erythema, facial edema, hirsutism, impaired wound healing, increased sweating, Karposi’s sarcoma (see PRECAUTIONS: General Precautions), lupus erythematosus-like lesions, perineal irritation, purpura, rash, striae, subcutaneous fat atrophy, suppression of reactions to skin tests, striae, telangiectasis, thin fragile skin, thinning scalp hair, urticaria.

Endocrine
Adrenal insufficiency-greatest potential caused by high potency glucocorticoids with long duration of action (associated symptoms include; arthralgias, buffalo hump, dizziness, life-threatening hypotension, nausea, severe tiredness or weakness), amenorrhea, postmenopausal bleeding or other menstrual irregularities, decreased carbohydrate and glucose tolerance, development of cushingoid state, diabetes mellitus (new onset or manifestations of latent), glycosuria, hyperglycemia, hypertrichosis, hyperthyroidism (see WARNINGS: Endocrine), hypothyroidism, increased requirements for insulin or oral hypoglycemic agents in diabetics, lipids abnormal, moon face, negative nitrogen balance caused by protein catabolism, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness) (see WARNINGS: Endocrine), suppression of growth in pediatric patients.

Fluid and Electrolyte Disturbances
congestive heart failure in susceptible patients, fluid retention, hypokalemia, hypokalemic alkalosis, metabolic alkalosis, hypotension or shock-like reaction, potassium loss, sodium retention with resulting edema.

Gastrointestinal
abdominal distention, abdominal pain, anorexia which may result in weight loss, constipation, diarrhea, elevation in serum liver enzyme levels (usually reversible upon discontinuation), gastric irritation, hepatomegaly, increased appetite and weight gain, nausea, oropharyngeal candidiasis, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis, vomiting.

Hematologic
anemia, neutropenia (including febrile neutropenia).

Metabolic
negative nitrogen balance due to protein catabolism.

Musculoskeletal
arthralgias, aseptic necrosis of femoral and humeral heads, increase risk of fracture, loss of muscle mass, muscle weakness, myalgias, osteopenia, osteoporosis (see PRECAUTIONS: Musculoskeletal), pathologic fracture of long bones, steroid myopathy, tendon rupture (particularly of the Achilles tendon), vertebral compression fractures.

Neurological/Psychiatric
amnesia, anxiety, benign intracranial hypertension, convulsions, delirium, dementia (characterized by deficits in memory retention, attention, concentration, mental speed and efficiency, and occupational performance), depression, dizziness, EEG abnormalities, emotional instability and irritability, euphoria, hallucinations, headache, impaired cognition, incidence of severe psychiatric symptoms, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, increased motor activity, insomnia, ischemic neuropathy, long-term memory loss, mania, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychiatric disorders including steroid psychoses or aggravation of pre-existing psychiatric conditions, restlessness, schizophrenia, verbal memory loss, vertigo, withdrawn behavior.

Ophthalmic
blurred vision, cataracts (including posterior subcapsular cataracts), central serous chorioretinopathy, establishment of secondary bacterial, fungal and viral infections, exophthalmos, glaucoma, increased intraocular pressure (see PRECAUTIONS: Ophthalmic), optic nerve damage, papilledema.

Other
abnormal fat deposits, aggravation/masking of infections, decreased resistance to infection (see WARNINGS: Infection), hiccups, immunosuppression, increased or decreased motility and number of spermatozoa, malaise, insomnia, moon face, pyrexia.

Vaccines

Patients on corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible (see WARNINGS: Infection: Vaccination).

PredniSONE 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, chloroform, dioxane, and methanol.

The chemical name for prednisone is pregna-1,4-diene-3,11,20-trione monohydrate,17,21-dihydroxy-. The structural formula is represented below:

PredniSONE Tablets are available in 5 strengths: 1 mg, 2.5 mg, 5 mg, 10 mg and 20 mg.

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.

PredniSONE Tablets are available in the following strengths and package sizes:

1 mg (white, round, flat-faced, beveled edge, scored, debossed “5084” on one side and debossed “V” on the reverse side)

• Bottles of 100                          NDC 0603-5335-21
• Bottles of 1000                        NDC 0603-5335-32

2.5 mg (white, round, flat-faced, beveled edge, scored, debossed “5085” on one side and debossed “V” on the reverse side)

• Bottles of 100                          NDC 0603-5336-21

5 mg (white, round, scored, debossed “5094” on one side and debossed “V” on the reverse side)

• Bottles of 100                          NDC 0603-5337-21
• Bottles of 1000                        NDC 0603-5337-32
• Unit-of-Use (21 Tablets)         NDC 0603-5337-15
• Unit-of-Use (48 Tablets)         NDC 0603-5337-31

10 mg (white, round, scored, debossed “5093” on one side and debossed “V” on the reverse side)

• Bottles of 100                          NDC 0603-5338-21
• Bottles of 500                          NDC 0603-5338-28
• Bottles of 1000                        NDC 0603-5338-32
• Unit-of-Use (21 Tablets)         NDC 0603-5338-15
• Unit-of-Use (48 Tablets)         NDC 0603-5338-31

20 mg (peach, round, scored, debossed “5092” on one side and debossed “V” on the reverse side)

• Bottles of 100                          NDC 0603-5339-21
• Bottles of 500                          NDC 0603-5339-28
• Bottles of 1000                        NDC 0603-5339-32

Ophthalmic

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 bacteria, fungi or viruses. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should not be used in active ocular herpes simplex because of possible corneal perforation.