Corticosteroids (Systemic)

CLINICAL PHARMACOLOGY
Budesonide has a high topical glucocorticosteroid (GCS) activity and a substantial first pass elimination. The formulation contains granules which are coated to protect dissolution in gastric juice, but which dissolve at pH >5.5, ie, normally when the granules reach the duodenum. Thereafter, a matrix of ethylcellulose with budesonide controls the release of the drug into the intestinal lumen in a time-dependent manner.

CONTRAINDICATIONS
ENTOCORT EC is contraindicated in patients with known hypersensitivity to budesonide.

WARNINGS
Glucocorticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic glucocorticosteroid is recommended. Since ENTOCORT EC is a glucocorticosteroid, general warnings concerning glucocorticoids should be followed.

Care is needed in patients who are transferred from glucocorticosteroid treatment with high systemic effects to corticosteroids with lower systemic availability, since symptoms attributed to withdrawal of steroid therapy, including those of acute adrenal suppression or benign intracranial hypertension, may develop. Adrenocortical function monitoring may be required in these patients and the dose of systemic steroid should be reduced cautiously.

Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressant doses of glucocorticosteroids. In patients who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route and duration of glucocorticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior glucocorticosteroid treatment to the risk is also not known. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package insert for complete VZIG and IG prescribing information.) If chicken pox develops, treatment with antiviral agents may be considered

Dosing:
Nasal inhalation: (Rhinocort® Aqua®): Children >/= 6 years and Adults: 64 mcg/day as a single 32 mcg spray in each nostril. Some patients who do not achieve adequate control may benefit from increased dosage. A reduced dosage may be effective after initial control is achieved.
Maximum dose: Children <12 years: 128 mcg/day; Adults: 256 mcg/day

Nebulization: Children 12 months to 8 years: Pulmicort Respules®: Titrate to lowest effective dose once patient is stable; start at 0.25 mg/day or use as follows:
Previous therapy of bronchodilators alone: 0.5 mg/day administered as a single dose or divided twice daily (maximum daily dose: 0.5 mg) .
Previous therapy of inhaled corticosteroids: 0.5 mg/day administered as a single dose or divided twice daily (maximum daily dose: 1 mg).
Previous therapy of oral corticosteroids: 1 mg/day administered as a single dose or divided twice daily (maximum daily dose: 1 mg).

Oral inhalation:
Children >/= 6 years:
Previous therapy of bronchodilators alone: 200 mcg twice initially which may be increased up to 400 mcg twice daily.
Previous therapy of inhaled corticosteroids: 200 mcg twice initially which may be increased up to 400 mcg twice daily.
Previous therapy of oral corticosteroids: The highest recommended dose in children is 400 mcg twice daily.

Adults:
Previous therapy of bronchodilators alone: 200-400 mcg twice initially which may be increased up to 400 mcg twice daily.
Previous therapy of inhaled corticosteroids: 200-400 mcg twice initially which may be increased up to 800 mcg twice daily.
Previous therapy of oral corticosteroids: 400-800 mcg twice daily which may be increased up to 800 mcg twice daily.

NIH Guidelines (NIH, 1997) (give in divided doses twice daily):
Children:
"Low" dose: 100-200 mcg/day
"Medium" dose: 200-400 mcg/day (1-2 inhalations/day)
"High" dose: >400 mcg/day (>2 inhalation/day)

Adults:
"Low" dose: 200-400 mcg/day (1-2 inhalations/day)
"Medium" dose: 400-600 mcg/day (2-3 inhalations/day)
"High" dose: >600 mcg/day (>3 inhalation/day)

Oral: Adults: Crohn's disease: 9 mg once daily in the morning; safety and efficacy have not been established for therapy duration >8 weeks; recurring episodes may be treated with a repeat 8-week course of treatment

Note: Treatment may be tapered to 6 mg once daily for 2 weeks prior to complete cessation. Patients receiving CYP3A4 inhibitors should be monitored closely for signs and symptoms of hypercorticism; dosage reduction may be required.

Supplied:
Capsule, enteric coated (Entocort™ EC): 3 mg.
Powder for oral inhalation (Pulmicort Turbuhaler®): 200 mcg/inhalation (104 g) [delivers ~160 mcg/inhalation; 200 metered doses] .

Additional dosage strengths available in Canada: 100 mcg/inhalation, 400 mcg/inhalation.
Suspension, nasal spray (Rhinocort® Aqua®): 32 mcg/inhalation (8.6 g) [120 metered doses].
Suspension for oral inhalation (Pulmicort Respules®): 0.25 mg/2 mL (30s), 0.5 mg/2 mL (30s).

Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli

CONTRAINDICATIONS
Systemic fungal infections and known hypersensitivity to components

Dosing:
If possible, administer glucocorticoids before 9 AM to minimize adrenocortical suppression; dosing depends upon the condition being treated and the response of the patient; Note: Supplemental doses may be warranted during times of stress in the course of withdrawing therapy
Children:
Anti-inflammatory or immunosuppressive: Oral: 2.5-10 mg/kg/day or 20-300 mg/m2 /day in divided doses every 6-8 hours
Physiologic replacement: Oral: 0.5-0.75 mg/kg/day or 20-25 mg/m2 /day in divided doses every 8 hours

Adults:
Anti-inflammatory or immunosuppressive: Oral: 25-300 mg/day in divided doses every 12-24 hours.
Physiologic replacement: Oral: 25-35 mg/day.

Supplied
Tablet, as acetate: 25 mg

Spinal cord compression: 10 to 100mg (Usually 10mg) IV stat, followed by 4 to 24 mg IV every 6 hours. Use larger doses (eg up to 100mg) in patients with profound neurologic injury and lower doses in patients with mild or equivocal signs.

Antiemetic: Prophylaxis: Oral, IV: 10-20 mg 15-30 minutes before treatment. Mildly emetogenic therapy: Oral, I.M., I.V.: 4 mg q4-6h. Delayed nausea/vomiting: Oral: 4-10 mg 1-2 times/day x 2-4 days.
Dexamethasone suppression test (depression indicator) (unlabeled use): Oral: 1 mg at 11 PM, draw blood at 8 AM the following day for plasma cortisol determination.
Cushing's syndrome, diagnostic: Oral: 1 mg at 11 PM, draw blood at 8 AM; greater accuracy for Cushing's syndrome may be achieved by the following:
Dexamethasone 0.5 mg by mouth every 6 hours for 48 hours (with 24-hour urine collection for 17-hydroxycorticosteroid excretion).

Multiple sclerosis (acute exacerbation): Oral: 30 mg/day for 1 week, followed by 4-12 mg/day for 1 month.
Treatment of shock: Addisonian crisis/shock (ie, adrenal insufficiency/responsive to steroid therapy): I.V. (given as sodium phosphate): 4-10 mg x 1, which may be repeated if necessary.
Unresponsive shock (ie, unresponsive to steroid therapy): I.V. (given as sodium phosphate): 1-6 mg/kg as a single I.V. dose or up to 40 mg initially followed by repeat doses every 2-6 hours while shock persists.
Physiological replacement: Oral, I.M., I.V. (should be given as sodium phosphate): 0.03-0.15 mg/kg/day or 0.6-0.75 mg/m2/day in divided doses every 6-12 hours.

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Administration
Oral: Administer with meals to decrease GI upset.

 I.M.: Acetate injection is not for I.V. use.

 I.V.: Administer as a 5-10 minute bolus; rapid injection is associated with a high incidence of perianal discomfort.

Dosing (Adults): 
Addison's Disease:   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 effects.   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.

Supplied:   0.1 mg tablet:

Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli

CONTRAINDICATIONS
Systemic fungal infections and known hypersensitivity to components

INDICATIONS AND USAGE
CORTEF 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
Non suppurative 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
Serum sickness
Bronchial asthma
Contact dermatitis
Atopic dermatitis
Drug hypersensitivity reactions

6. Ophthalmic Diseases
Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as:

Allergic conjunctivitis
Keratitis
Allergic corneal marginal ulcers
Herpes zoster ophthalmicus
Iritis and iridocyclitis
Chorioretinitis
Anterior segment inflammation
Diffuse posterior uveitis and choroiditis
Optic neuritis
Sympathetic ophthalmia

7. 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

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. Nervous System
Acute exacerbations of multiple sclerosis

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

Dosing:
Dose should be based on severity of disease and patient response
Acute adrenal insufficiency: I.M., I.V.:
 Infants and young Children: Succinate: 1-2 mg/kg/dose bolus, then 25-150 mg/day in divided doses every 6-8 hours.
Older Children: Succinate: 1 to 2 mg/kg bolus then 150-250 mg/day in divided doses every 6-8 hours.
Adults: Succinate: 100 mg I.V. bolus, then 300 mg/day in divided doses every 8 hours or as a continuous infusion for 48 hours; once patient is stable change to oral, 50 mg every 8 hours for 6 doses, then taper to 30-50 mg/day in divided doses

Chronic adrenal corticoid insufficiency:
Adults: Oral: 20-30 mg/day

Anti-inflammatory or immunosuppressive:
 Infants and Children:
Oral: 2.5 to 10 mg/kg/day or 75 to 300 mg/m²/day every 6-8 hours.
I.M., I.V.: Succinate: 1 to 5 mg/kg/day or 30-150 mg/m²/day divided every 12 to 24 hours.

Adolescents and Adults: Oral, I.M., I.V.: Succinate: 15 to 240 mg every 12 hours.

Congenital adrenal hyperplasia: Oral: Initial: 10 to 20 mg/m² /day in 3 divided doses; a variety of dosing schedules have been used. Note: Inconsistencies have occurred with liquid formulations; tablets may provide more reliable levels. Doses must be individualized by monitoring growth, bone age, and hormonal levels. Mineralocorticoid and sodium supplementation may be required based upon electrolyte regulation and plasma renin activity.

Physiologic replacement:
Children:
Oral: 0.5-0.75 mg/kg/day or 20-25 mg/m²/day every 8 hours
I.M.: Succinate: 0.25 to 0.35 mg/kg/day or 12-15 mg/m²/day once daily

Shock: I.M., I.V.: Succinate:
Children: Initial: 50 mg/kg, then repeated in 4 hours and/or every 24 hours as needed
Adolescents and Adults: 500 mg to 2 g every 2 to 6 hours

Status asthmaticus:
Children and Adults: I.V.: Succinate: 1-2 mg/kg/dose every 6 hours for 24 hours, then maintenance of 0.5-1 mg/kg every 6 hours

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Adults:
Rheumatic diseases:
Intralesional, intra-articular, soft tissue injection: Acetate:
Large joints: 25 mg (up to 37.5 mg)
Small joints: 10-25 mg
Tendon sheaths: 5-12.5 mg
Soft tissue infiltration: 25-50 mg (up to 75 mg)
Bursae: 25-37.5 mg
Ganglia: 12.5-25 mg

Stress dosing (surgery) in patients known to be adrenally-suppressed or on chronic systemic steroids: I.V.:
Minor stress (ie, inguinal herniorrhaphy): 25 mg/day for 1 day.
Moderate stress (ie, joint replacement, cholecystectomy): 50-75 mg/day (25 mg every 8-12 hours) for 1-2 days.
Major stress (pancreatoduodenectomy, esophagogastrectomy, cardiac surgery): 100-150 mg/day (50 mg every 8-12 hours) for 2-3 days.

Dermatosis: Children >2 years and Adults: Topical: Apply to affected area 2-4 times/day (Buteprate: Apply once or twice daily). Therapy should be discontinued when control is achieved; if no improvement is seen, reassessment of diagnosis may be necessary.

Ulcerative colitis:
Adults: Rectal: 10-100 mg 1-2 times/day for 2-3 weeks

Administration
Oral: Administer with food or milk to decrease GI upset.
Parenteral: Hydrocortisone sodium succinate may be administered by I.M. or I.V. routes.
I.V. bolus: Dilute to 50 mg/mL and administer over 30 seconds to several minutes (depending on the dose) .
I.V. intermittent infusion: Dilute to 1 mg/mL and administer over 20-30 minutes.
Topical: Apply a thin film to clean, dry skin and rub in gently.

Methylprednisolone sodium succinate has the same metabolic and anti-inflammatory actions as methylprednisolone. When given parenterally and in equimolar quantities, the two compounds are equivalent in biologic activity. The relative potency of A-Methapred sterile powder and hydrocortisone sodium succinate, as indicated by depression of eosinophil count, following intravenous administration, is at least four to one. This is in good agreement with the relative oral potency of methylprednisolone and hydrocortisone.

DOSING:
Dosing should be based on the lesser of ideal body weight or actual body weight
Only sodium succinate may be given I.V.; methylprednisolone sodium succinate is highly soluble and has a rapid effect by I.M. and I.V. routes. Methylprednisolone acetate has a low solubility and has a sustained I.M. effect.

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Children:
Anti-inflammatory or immunosuppressive: Oral, I.M., I.V. (sodium succinate): 0.5-1.7 mg/kg/day or 5-25 mg/m 2 /day in divided doses every 6-12 hours; "Pulse" therapy: 15-30 mg/kg/dose over >/= 30 minutes given once daily for 3 days

Status asthmaticus: I.V. (sodium succinate): Loading dose: 2 mg/kg/dose, then 0.5-1 mg/kg/dose every 6 hours for up to 5 days

Acute spinal cord injury: I.V. (sodium succinate): 30 mg/kg over 15 minutes, followed in 45 minutes by a continuous infusion of 5.4 mg/kg/hour for 23 hours

Lupus nephritis: I.V. (sodium succinate): 30 mg/kg over >/= 30 minutes every other day for 6 doses
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Adults: Only sodium succinate may be given I.V.; methylprednisolone sodium succinate is highly soluble and has a rapid effect by I.M. and I.V. routes. Methylprednisolone acetate has a low solubility and has a sustained I.M. effect.

Acute spinal cord injury: I.V. (sodium succinate): 30 mg/kg over 15 minutes, followed in 45 minutes by a continuous infusion of 5.4 mg/kg/hour for 23 hours

Anti-inflammatory or immunosuppressive:
Oral: 2-60 mg/day in 1-4 divided doses to start, followed by gradual reduction in dosage to the lowest possible level consistent with maintaining an adequate clinical response.

I.M. (sodium succinate): 10 to 80 mg/day once daily
I.M. (acetate): 10 to 80 mg every 1-2 weeks

I.V. (sodium succinate): 10 to 40 mg over a period of several minutes and repeated I.V. or I.M. at intervals depending on clinical response; when high dosages are needed, give 30 mg/kg over a period >/= 30 minutes and may be repeated every 4 to 6 hours for 48 hours.

Status asthmaticus: I.V. (sodium succinate): Loading dose: 2 mg/kg/dose, then 0.5-1 mg/kg/dose every 6 hours for up to 5 days

High-dose therapy for acute spinal cord injury: I.V. bolus: 30 mg/kg over 15 minutes, followed 45 minutes later by an infusion of 5.4 mg/kg/hour for 23 hours

Lupus nephritis: High-dose "pulse" therapy: I.V. (sodium succinate): 1 g/day for 3 days

Aplastic anemia: I.V. (sodium succinate): 1 mg/kg/day or 40 mg/day (whichever dose is higher), for 4 days. After 4 days, change to oral and continue until day 10 or until symptoms of serum sickness resolve, then rapidly reduce over approximately 2 weeks.

Pneumocystis pneumonia in AIDs patients: I.V.: 40-60 mg every 6 hours for 7-10 days

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 Intra-articular (acetate): Administer every 1-5 weeks.
Large joints: 20-80 mg
Small joints: 4-10 mg
Intralesional (acetate): 20-60 mg every 1-5 weeks

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Administration
Oral: Administer after meals or with food or milk

Parenteral: Methylprednisolone sodium succinate may be administered I.M. or I.V.; I.V. administration may be IVP over one to several minutes or IVPB or continuous I.V. infusion. Acetate salt should not be given I.V.

I.V.: Succinate:
Low dose: </= 1.8 mg/kg or </= 125 mg/dose: I.V. push over 3-15 minutes
Moderate dose: >/= 2 mg/kg or 250 mg/dose: I.V. over 15-30 minutes
High dose: 15 mg/kg or >/= 500 mg/dose: I.V. over >/= 30 minutes
Doses >15 mg/kg or >/= 1 g: Administer over 1 hour

Do not administer high-dose I.V. push; hypotension, cardiac arrhythmia, and sudden death have been reported in patients given high-dose methylprednisolone I.V. push over <20 minutes; intermittent infusion over 15-60 minutes; maximum concentration: I.V. push 125 mg/mL

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SUPPLIED
Injection, powder for reconstitution, as sodium succinate: 125 mg [strength expressed as base]
Solu-Medrol®: 40 mg, 125 mg, 500 mg, 1 g, 2 g [packaged with diluent; diluent contains benzyl alcohol; strength expressed as base]
Solu-Medrol®: 500 mg, 1 g

Injection, suspension, as acetate (Depo-Medrol®): 20 mg/mL (5 mL); 40 mg/mL (5 mL); 80 mg/mL (5 mL) [contains benzyl alcohol; strength expressed as base]

Injection, suspension, as acetate [single-dose vial] (Depo-Medrol®): 40 mg/mL (1 mL, 10 mL); 80 mg/mL (1 mL)

Tablet: 4 mg
Medrol®: 2 mg, 4 mg, 8 mg, 16 mg, 32 mg
Tablet, dose-pack: 4 mg (21s)
Medrol® Dosepack™: 4 mg (21s)

Acute asthma: 1-2 mg/kg/day in divided doses 1-2 times/day for 3-5 days

Alternatively (for 3- to 5-day "burst"):
<1 year: 10 mg every 12 hours
1-4 years: 20 mg every 12 hours
5-13 years: 30 mg every 12 hours
>13 years: 40 mg every 12 hours

Asthma long-term therapy (alternative dosing by age):
<1 year: 10 mg every other day
1-4 years: 20 mg every other day
5-13 years: 30 mg every other day
>13 years: 40 mg every other day

Nephrotic syndrome:
Initial (first 3 episodes): 2 mg/kg/day or 60 mg/m2 /day (maximum: 80 mg/day) in divided doses 3-4 times/day until urine is protein free for 3 consecutive days (maximum: 28 days); followed by 1-1.5 mg/kg/dose or 40 mg/m2 /dose given every other day for 4 weeks

Maintenance dose (long-term maintenance dose for frequent relapses): 0.5-1 mg/kg/dose given every other day for 3-6 months

Children and Adults:
Physiologic replacement: 4-5 mg/m2 /day

Children >/= 5 years and Adults:
Asthma:
Moderate persistent: Inhaled corticosteroid (medium dose) or inhaled corticosteroid (low-medium dose) with a long-acting bronchodilator

Severe persistent: Inhaled corticosteroid (high dose) and corticosteroid tablets or syrup long term: 2 mg/kg/day, generally not to exceed 60 mg/day

Adults:
Immunosuppression/chemotherapy adjunct: Range: 5 to 60 mg/day in divided doses 1-4 times/day

Allergic reaction (contact dermatitis):
Day 1: 30 mg divided as 10 mg before breakfast, 5 mg at lunch, 5 mg at dinner, 10 mg at bedtime
Day 2: 5 mg at breakfast, 5 mg at lunch, 5 mg at dinner, 10 mg at bedtime
Day 3: 5 mg 4 times/day (with meals and at bedtime)
Day 4: 5 mg 3 times/day (breakfast, lunch, bedtime)
Day 5: 5 mg 2 times/day (breakfast, bedtime)
Day 6: 5 mg before breakfast

Pneumocystis carinii pneumonia (PCP):
40 mg twice daily for 5 days followed by
40 mg once daily for 5 days followed by
20 mg once daily for 11 days or until antimicrobial regimen is completed

Thyrotoxicosis: Oral: 60 mg/day

Chemotherapy (refer to individual protocols): Oral: Range: 20 mg/day to 100 mg/m 2 /day

Rheumatoid arthritis: Oral: Use lowest possible daily dose (often </= 7.5 mg/day)

Idiopathic thrombocytopenia purpura (ITP): Oral: 60 mg daily for 4-6 weeks, gradually tapered over several weeks

Systemic lupus erythematosus (SLE): Oral:
Acute: 1-2 mg/kg/day in 2-3 divided doses
Maintenance: Reduce to lowest possible dose, usually <1 mg/kg/day as single dose (morning)

Elderly: Use the lowest effective dose

PACKAGE INSERT DATA
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.