Introduction

Synthetic glucocorticoid; minimal mineralocorticoid activity.

Uses for prednisoLONE (Systemic)

Treatment of a wide variety of diseases and conditions, principally for glucocorticoid effects as an anti-inflammatory and immunosuppressant agent and for its effects on blood and lymphatic systems in the palliative treatment of various diseases.

Adrenocortical Insufficiency

Corticosteroids are administered in physiologic dosages to replace deficient endogenous hormones in patients with adrenocortical insufficiency.

Because production of both mineralocorticoids and glucocorticoids is deficient in adrenocortical insufficiency, hydrocortisone or cortisone (in conjunction with liberal salt intake) usually is the corticosteroid of choice for replacement therapy.

Usually inadequate alone for adrenocortical insufficiency because of minimal mineralocorticoid activity.

If prednisolone is used for adrenocortical insufficiency, a mineralocorticoid (e.g., fludrocortisone) must also be administered, particularly in infants.

Adrenogenital Syndrome

Lifelong glucocorticoid treatment of adrenogenital syndrome (e.g., congenital adrenal hyperplasia).

In salt-losing forms, cortisone or hydrocortisone is preferred in conjunction with liberal salt intake; concomitant use of a mineralocorticoid may be necessary until the patient is at least 5–7 years of age.

For long-term therapy after early childhood, a glucocorticoid alone usually is sufficient.

In hypertensive forms, a “short-acting” glucocorticoid with minimal mineralocorticoid activity (e.g., methylprednisolone, prednisone) is preferred. Avoid long-acting glucocorticoids (e.g., dexamethasone) because of tendency toward overdosage and growth retardation.

Hypercalcemia

Treatment of hypercalcemia associated with malignancy.

Usually ameliorates hypercalcemia associated with bone involvement in multiple myeloma.

Treatment of hypercalcemia associated with sarcoidosis^{† [off-label]}.

Treatment of hypercalcemia associated with vitamin D intoxication^{† [off-label]}.

Not effective for hypercalcemia caused by hyperparathyroidism^{† [off-label]}.

Thyroiditis

Treatment of granulomatous (subacute, nonsuppurative) thyroiditis.

Anti-inflammatory actions relieves fever, acute thyroid pain, and swelling.

May reduce orbital edema in endocrine exophthalmos (thyroid ophthalmopathy).

Usually reserved for palliative therapy in severely ill patients unresponsive to salicylates and thyroid hormones.

Rheumatic Disorders and Collagen Diseases

Short-term palliative treatment of acute episodes or exacerbations and systemic complications of rheumatic disorders (e.g., rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, acute gouty arthritis, posttraumatic osteoarthritis, synovitis of osteoarthritis, epicondylitis, acute nonspecific tenosynovitis, ankylosing spondylitis, Reiter's syndrome^{† [off-label]}, rheumatic fever^{† [off-label]} [especially with carditis]) and collagen diseases (e.g., acute rheumatic carditis, systemic lupus erythematosus, systemic dermatomyositis^† [polymyositis], polyarteritis nodosa^†, vasculitis^†) refractory to more conservative measures.

Relieves inflammation and suppresses symptoms but not disease progression.

Rarely indicated as maintenance therapy.

May be used as maintenance therapy (e.g., in rheumatoid arthritis, acute gouty arthritis, systemic lupus erythematosus, acute rheumatic carditis) as part of a total treatment program in selected patients when more conservative therapies have proven ineffective.

Glucocorticoid withdrawal is extremely difficult if used for maintenance; relapse and recurrence usually occur with drug discontinuance.

Controls acute manifestations of rheumatic carditis more rapidly than salicylates and may be life-saving; cannot prevent valvular damage and no better than salicylates for long-term treatment.

Adjunctively for severe systemic complications of Wegener’s granulomatosis^†, but cytotoxic therapy is the treatment of choice.

Primary treatment to control symptoms and prevent severe, often life-threatening complications of systemic lupus erythematosus, systemic dermatomyositis (polymyositis), polyarteritis nodosa^†, relapsing polychondritis, polymyalgia rheumatica, Sjögren's syndrome, giant-cell (temporal) arteritis^†, certain cases of vasculitis, or mixed connective tissue disease syndrome^†. High dosage may be required for acute situations; after a response has been obtained, the drug must often be continued for long periods at low dosage.

Polymyositis^† associated with malignancy and childhood dermatomyositis may not respond well.

Rarely indicated in psoriatic arthritis, diffuse scleroderma^† (progressive systemic sclerosis), or osteoarthritis; risks outweigh benefits.

Dermatologic Diseases

Treatment of pemphigus and pemphigoid^†, bullous dermatitis herpetiformis, severe erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, uncontrollable eczema^†, cutaneous sarcoidosis^†, mycosis fungoides, lichen planus^†, severe psoriasis, and severe seborrheic dermatitis.

Usually reserved for acute exacerbations unresponsive to conservative therapy.

Early initiation of systemic glucocorticoid therapy may be life-saving in pemphigus vulgaris and pemphigoid^†, and high or massive doses may be required.

For control of severe or incapacitating allergic conditions (e.g., contact dermatitis, atopic dermatitis) refractory to adequate trials of conventional treatment.

Chronic skin disorders seldom an indication for systemic glucocorticoid therapy.

Used for severe psoriasis but rarely indicated systemically; if used, exacerbation may occur when the drug is withdrawn or dosage is decreased.

Rarely indicated systemically for alopecia areata^†, alopecia totalis^†, or alopecia universalis^†. May stimulate hair growth, but hair loss returns when the drug is discontinued.

Allergic Conditions

For control of severe or incapacitating allergic conditions unresponsive to adequate trials of conventional treatment; for control of acute manifestations, including angioedema^†, serum sickness, allergic symptoms of trichinosis^†, urticarial transfusion reactions, drug hypersensitivity reactions, and severe seasonal or perennial rhinitis.

Systemic therapy usually reserved for acute conditions and severe exacerbations.

For acute conditions, usually used in high dosage and with other therapies (e.g., antihistamines, sympathomimetics).

Reserve prolonged treatment of chronic allergic conditions to disabling conditions unresponsive to more conservative therapy and when risks of long-term glucocorticoid therapy are justified.

Ocular Disorders

To suppress a variety of allergic and nonpyogenic ocular inflammations.

To reduce scarring in ocular injuries^†.

For the treatment of severe acute and chronic allergic and inflammatory processes involving the eye and adnexa, including 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.

Less severe allergic and inflammatory allergic conditions of the eye are treated with topical ophthalmic corticosteroids.

Systemically in stubborn cases of anterior segment eye disease and when deeper ocular structures are involved.

Asthma

Corticosteroids are used as adjunctive treatment of acute asthma exacerbations^† and for maintenance treatment of persistent asthma^†.

Systemic glucocorticoids (usually prednisone, prednisolone, and dexamethasone) are used for treatment of moderate to severe acute exacerbations of asthma; speeds resolution of airflow obstruction and reduces rate of relapse.

Chronic Obstructive Pulmonary Disease

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline states that oral glucocorticoids play a role in the acute management of COPD exacerbations, but have no role in the chronic daily treatment of COPD because of the lack of benefit and high rate of systemic complications.

Sarcoidosis

Management of symptomatic sarcoidosis.

Systemic glucocorticoids are indicated for hypercalcemia; ocular, CNS, glandular, myocardial, or severe pulmonary involvement; or severe skin lesions unresponsive to intralesional injections of glucocorticoids.

Tuberculosis

Treatment of fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous therapy.

Eosinophilic Pneumonias

Used in the management of idiopathic eosinophilic pneumonias.

Hypersensitivity Pneumonitis

Used in the management of hypersensitivity pneumonitis.

Pulmonary Fibrosis

Used in the management of idiopathic pulmonary fibrosis.

Lipid Pneumonitis†

Promotes the breakdown or dissolution of pulmonary lesions and eliminates sputum lipids.

Pneumocystis carinii Pneumonia

Corticosteroids are used adjunctively in the treatment of Pneumocystis jiroveci (Pneumocystis carinii) pneumonia.

Allergic Bronchopulmonary Aspergillosis

Used in the management of allergic bronchopulmonary aspergillosis.

Bronchiolitis Obliterans

Used in the management of idiopathic bronchiolitis obliterans with organizing pneumonia.

Loeffler’s Syndrome

Symptomatic relief of acute manifestations of symptomatic Loeffler’s syndrome not manageable by other means.

Berylliosis

Symptomatic relief of acute manifestations of berylliosis.

Aspiration Pneumonitis

Symptomatic relief of acute manifestations of aspiration pneumonitis.

Anthrax

Has been used as an adjunct to anti-infective therapy in the treatment of anthrax^†; evidence of effect based on small observational studies. Some clinicians recommend that adjunctive corticosteroids be considered in patients with extensive edema especially of the head or neck, suspected bacterial meningitis, or vasopressor-resistant shock.

Hematologic Disorders

Management of acquired (autoimmune) hemolytic anemia, idiopathic thrombocytopenic purpura (ITP), secondary thrombocytopenia, erythroblastopenia, congenital (erythroid) hypoplastic anemia (Diamond-Blackfan anemia), or hemolysis^†.

High or even massive dosages decrease bleeding tendencies and normalize blood counts; does not affect the course or duration of hematologic disorders.

Glucocorticoids, immune globulin IV (IGIV), or splenectomy are first-line therapies for moderate to severe ITP, depending on the extent of bleeding involved.

May not affect or prevent renal complications in Henoch-Schoenlein purpura.

Insufficient evidence of effectiveness in aplastic anemia in children, but widely used.

GI Diseases

Short-term palliative therapy for acute exacerbations and systemic complications of ulcerative colitis or regional enteritis, or celiac disease^†. Low dosages of glucocorticoids, in conjunction with other supportive therapy, may occasionally be useful for patients unresponsive to usual therapy for chronic conditions.

Do not use if a probability of impending perforation, abscess, or other pyogenic infection.

Crohn’s Disease

Oral corticosteroids may be used for short-term treatment of moderate to severely active Crohn’s disease^†.

Neoplastic Diseases

Alone or as a component of various chemotherapeutic regimens in the palliative treatment of neoplastic diseases of the lymphatic system (e.g., leukemias and lymphomas in adults and acute leukemias in children).

In adults, acute lymphocytic (lymphoblastic) leukemia, chronic lymphocytic leukemia, and Hodgkin’s disease respond well to combination regimens that include a glucocorticoid (usually prednisone or prednisolone). Acute myeloblastic leukemia, lymphosarcoma, and the blast crisis of chronic myelocytic leukemia may fail to respond or may relapse upon discontinuance of therapy.

Liver Disease

In patients with subacute hepatic necrosis^† and chronic active hepatitis^†, high-dose glucocorticoids can decrease serum bilirubin, ascites, and mortality rate. In nonalcoholic cirrhosis^† in women, the drugs increase survival rate in the absence of ascites, but not when ascites is present. May decrease mortality rate in patients with alcoholic cirrhosis with hepatic encephalopathy^†, but should not be used in less seriously ill patients.

Myasthenia Gravis

Corticosteroids have been used in the management of myasthenia gravis^†, usually when there is an inadequate response to anticholinesterase therapy.

Organ Transplants

Used in massive dosage with or without other immunosuppressive drugs to prevent rejection of transplanted organs^†.

Incidence of secondary infections is high with immunosuppressive drugs; limit to clinicians experienced in their use.

Trichinosis

Treatment of trichinosis with neurologic or myocardial involvement.

Nephrotic Syndrome and Lupus Nephritis

Treatment of idiopathic nephrotic syndrome without uremia.

Can induce diuresis or remission of proteinuria in nephrotic syndrome secondary to primary renal disease, especially when there is minimal renal histologic change.

Treatment of lupus nephritis.

prednisoLONE (Systemic) Dosage and Administration

General

• Route of administration and dosage depend on the condition being treated and the patient response.

Alternate-day Therapy

• Alternate-day therapy in which a single dose (twice the usual daily dosage) is administered every other morning is the dosage regimen of choice for long-term oral glucocorticoid treatment of most conditions. This regimen provides relief of symptoms while minimizing adrenal suppression, protein catabolism, and other adverse effects.

• If alternate-day therapy is preferred, only use a “short-acting” glucocorticoid that suppresses the HPA axis <1.5 days after a single oral dose (e.g., prednisone, prednisolone, methylprednisolone).

• Some conditions (e.g., rheumatoid arthritis, ulcerative colitis) require daily glucocorticoid therapy because symptoms of the underlying disease cannot be controlled by alternate-day therapy.

Discontinuance of Therapy

• A steroid withdrawal syndrome consisting of lethargy, fever, myalgia can develop following abrupt discontinuance. Symptoms often occur without evidence of adrenal insufficiency (while plasma glucocorticoid concentrations were still high but were falling rapidly).

• If used for only brief periods (a few days) in emergency situations, may reduce and discontinue dosage quite rapidly.

• Very gradually withdraw systemic glucocorticoids until recovery of HPA-axis function occurs following long-term therapy with pharmacologic dosages. (See Adrenocortical Insufficiency under Warnings.)

• Exercise caution when transferring from systemic glucocorticoid to oral or nasal inhalation corticosteroid therapy.

• Many methods of slow withdrawal or “tapering” have been described.

• In 1 suggested regimen, decrease by 2.5–5 mg every 3–7 days until the physiologic dose (5 mg) is reached.

• Other recommendations state that decrements usually should not exceed 2.5 mg every 1–2 weeks.

• When a physiologic dosage has been reached, single 20-mg oral morning doses of hydrocortisone can be substituted for whatever glucocorticoid the patient has been receiving. After 2–4 weeks, may decrease hydrocortisone dosage by 2.5 mg every week until a single morning dosage of 10 mg daily is reached.

• For certain acute allergic conditions (e.g., contact dermatitis such as poison ivy) or acute exacerbations of chronic allergic conditions, glucocorticoids may be administered short term (e.g., for 6 days). Administer a high dose on the first day of therapy, then withdraw therapy by tapering the dosage over several days.

Administration

Oral Administration

Administer orally as tablets, syrup, or oral solution.

Dosage

Dosage of prednisolone sodium phosphate is expressed in terms of prednisolone.

After a satisfactory response is obtained, decrease dosage in small decrements to the lowest level that maintains an adequate clinical response, and discontinue the drug as soon as possible.

Monitor patients continually for signs that indicate dosage adjustment is necessary, such as remissions or exacerbations of the disease and stress (surgery, infection, trauma).

High dosages may be required for acute situations of certain rheumatic disorders and collagen diseases. After a response has been obtained, drug often must be continued for long periods at low dosage.

High or massive dosages may be required in the treatment of pemphigus, exfoliative dermatitis, bullous dermatitis herpetiformis, severe erythema multiforme, or mycosis fungoides. Early initiation of systemic glucocorticoid therapy may be life-saving in pemphigus vulgaris. Reduce dosage gradually to the lowest effective level, but discontinuance may not be possible.

Pediatric Patients

Base pediatric dosage on severity of the disease and patient response rather than on strict adherence to dosage indicated by age, body weight, or body surface area.

Usual Dosage

Oral

Syrup or tablets: Initially, 0.14–2 mg/kg daily or 4–60 mg/m² daily in 4 divided doses.

Oral solution: Initially, 0.14–2 mg/kg daily or 4–60 mg/m² daily in 3 or 4 divided doses.

Asthma

Oral

For the treatment of refractory bronchial asthma and related bronchospasm (severe persistent asthma) not controlled with high maintenance dosages of an inhaled corticosteroid and a long-acting bronchodilator, add an oral corticosteroid (e.g., prednisone, prednisolone, methylprednisolone) at a dosage of 1–2 mg/kg daily in single or divided doses. Continue a short course of oral corticosteroid therapy (usually 3–10 days) until a peak expiratory flow rate of 80% of personal best is achieved or until symptoms resolve. May need a longer duration of treatment in some children. No evidence that tapering the dosage after improvement will prevent relapse.

Nephrotic Syndrome

Oral

Usual dosage: 60 mg/m² given in 3 divided doses for 4 weeks, followed by 4 weeks of alternate-day therapy at single doses of 40 mg/m².

Adults

Usual Dosage

Oral

Initially, 5–60 mg daily, depending on the disease being treated; usually administered in 2–4 divided doses.

Acute Exacerbations of Multiple Sclerosis

Oral

Usual dosage: 200 mg daily for 1 week, followed by 80 mg every other day for a month.

Contraindications

• Known hypersensitivity to prednisolone, any ingredient in the respective formulation, or any other corticosteroid.

• Systemic fungal infections.

• Concurrent administration of live or live, attenuated vaccines in patients receiving immunosuppressive doses of corticosteroids. (See Specific Drugs and Laboratory Tests under Interactions.)

Warnings/Precautions

Warnings

Adrenocortical Insufficiency

When given in supraphysiologic doses for prolonged periods, glucocorticoids may cause decreased secretion of endogenous corticosteroids by suppressing pituitary release of corticotropin (secondary adrenocortical insufficiency).

The degree and duration of adrenocortical insufficiency is highly variable among patients and depends on the dose, frequency and time of administration, and duration of glucocorticoid therapy.

Acute adrenal insufficiency (even death) may occur if the drugs are withdrawn abruptly or if patients are transferred from systemic glucocorticoid therapy to local (e.g., inhalation) therapy.

Withdraw prednisolone very gradually following long-term therapy with pharmacologic dosages. (See Discontinuance of Therapy under Dosage and Administration: Dosage.)

Adrenal suppression may persist up to 12 months in patients who receive large dosages for prolonged periods.

Until recovery occurs, signs and symptoms of adrenal insufficiency may develop if subjected to stress (e.g., infection, surgery, trauma, illness) and replacement therapy may be required. Since mineralocorticoid secretion may be impaired, sodium chloride and/or a mineralocorticoid also should be administered.

If the disease flares up during withdrawal, may need to increase dosage temporarily and then withdraw drug more gradually.

Immunosuppression

Increased susceptibility to infections secondary to glucocorticoid-induced immunosuppression. Certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients. (See Increased Susceptibility to Infection under Warnings.)

Administration of live virus vaccines, including smallpox, is contraindicated in patients receiving immunosuppressive dosages of glucocorticoids. In addition, if inactivated viral or bacterial vaccines are administered to such patients, expected serum antibody response may not be obtained. The USPHS Advisory Committee on Immunization Practices (ACIP) and American Academy of Family Physicians (AAFP) state that administration of live virus vaccines usually is not contraindicated in patients receiving corticosteroid therapy under the following circumstances:

• short-term (<2 weeks) therapy

• low to moderate dosage

• long-term alternate-day treatment with long-acting preparations

• maintenance physiologic dosages (replacement therapy)

• if it is administered topically, ophthalmically, intra-articularly, bursally, or into a tendon

Increased Susceptibility to Infection

Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection.

Infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic infections in any organ system may be associated with glucocorticoids alone or in combination with other immunosuppressive agents; reactivation of latent infections may occur.

Infections may be mild, but they can be severe or fatal, and localized infections may disseminate.

Do not use, except in life-threatening situations, in patients with viral infections, or bacterial infections not controlled by anti-infectives.

Some infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome, particularly in children.

Children and adults who are not likely to have been exposed to varicella or measles should avoid exposure to these infections while receiving glucocorticoids.

If exposure to varicella or measles occurs in susceptible patients, treat appropriately (e.g., VZIG, IG, acyclovir).

Use with great care in patients with known or suspected Strongyloides (threadworm) infection. Immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Not effective and can have detrimental effects in the management of cerebral malaria.

Can reactivate tuberculosis. Include chemoprophylaxis in patients with a history of active tuberculosis undergoing prolonged glucocorticoid therapy. Observe closely for evidence of reactivation. Restrict use in active tuberculosis to those with fulminating or disseminated tuberculosis in which glucocorticoids are used in conjunction with appropriate antimycobacterial chemotherapy.

Can reactivate latent amebiasis. Exclude possible amebiasis in any patient who has been in the tropics or who has unexplained diarrhea prior to initiating therapy.

Musculoskeletal Effects

Muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones are manifestations of protein catabolism that may occur during prolonged therapy with glucocorticoids. These adverse effects may be especially serious in geriatric or debilitated patients. A high protein diet may help to prevent adverse effects associated with protein catabolism.

An acute, generalized myopathy can occur with the use of high doses of glucocorticoids, particularly in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis) or in patients receiving concomitant therapy with neuromuscular blocking agents (e.g., pancuronium).

Osteoporosis and related fractures are one of the most serious adverse effects of long-term glucocorticoid therapy. The American College of Rheumatology (ACR) has published guidelines on prevention and treatment of glucocorticoid-induced osteoporosis. Recommendations are made according to a patient's risk of fracture.

Fluid and Electrolyte Disturbances

Sodium retention with resultant edema, potassium loss, and elevation of blood pressure may occur but is less common with prednisolone than with average or large doses of cortisone or hydrocortisone. Risk is increased with high-dose synthetic glucocorticoids for prolonged periods. Edema and CHF (in susceptible patients) may occur.

Dietary salt restriction is advisable and potassium supplementation may be necessary.

Increased calcium excretion and possible hypocalcemia.

Ocular Effects

Prolonged use may result in posterior subcapsular and nuclear cataracts (particularly in children), exophthalmos, and/or increased IOP which may result in glaucoma or may occasionally damage the optic nerve. If corticosteroid therapy is continued for >6 weeks, monitor IOP.

May enhance the establishment of secondary fungal, bacterial, and viral infections of the eye.

Do not use in patients with active ocular herpes simplex infections for fear of corneal perforation.

Endocrine and Metabolic Effects

With prolonged therapy, may produce various endocrine disorders including hypercorticism (cushingoid state) and amenorrhea or other menstrual difficulties.

Increased or decreased motility and number of sperm in some men.

May decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus, especially in patients predisposed to diabetes mellitus. If glucocorticoid therapy is required in patients with diabetes mellitus, may be necessary to change insulin or oral antidiabetic agent dosage or diet.

Exaggerated response to glucocorticoids in hypothyroidism.

Cardiovascular Effects

Use with extreme caution in recent MI since an association between use of glucocorticoids and left ventricular free-wall rupture has been suggested.

Sodium retention with resultant edema, potassium loss, hypokalemic alkalosis, and hypertension may occur in patients receiving glucocorticoids. Congestive heart failure may occur in susceptible patients.

Should be used with caution in patients with hypertension or congestive heart failure.

Sensitivity Reactions

Urticaria and other allergic, anaphylactic, or hypersensitivity reactions reported.

General Precautions

Monitoring

Prior to initiation of long-term glucocorticoid therapy, perform baseline ECGs, BPs, chest and spinal radiographs, glucose tolerance tests, and evaluations of HPA-axis function in all patients.

Perform upper GI radiographs in patients predisposed to GI disorders, including those with known or suspected peptic ulcer disease.

During long-term therapy, perform periodic height and weight determinations, chest and spinal radiographs, and hematopoietic, electrolyte, glucose tolerance, ocular pressure, and BP evaluations.

Genitourinary Effects

Increased or decreased motility and number of sperm in some men.

Nervous System Effects

May precipitate mental disturbances ranging from euphoria, insomnia, mood swings, depression, and personality changes to frank psychoses. Use may aggravate emotional instability or psychotic tendencies.

Use with caution in patients with myasthenia gravis.

GI Effects

Use with caution in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or those with recent intestinal anastomoses.

Signs of peritoneal irritation following GI perforation may be absent in patients receiving corticosteroids.

Use with caution in patients with active or latent peptic ulcer. Suggest concurrent administration of antacids between meals to prevent peptic ulcer formation in patients receiving high dosages of corticosteroids.

Dermatologic Effects

Kaposi’s sarcoma has been reported to occur in patients receiving glucocorticoid therapy; discontinuance of such therapy may result in remission of the disease.

Specific Populations

Pregnancy

Corticosteroids have been shown to be teratogenic in many species when administered in clinical doses. No adequate and well-controlled studies in pregnant women. Use during pregnancy only potential benefit justifies potential risk to fetus.

Lactation

Glucocorticoids are distributed into milk and could suppress growth, interfere with endogenous glucocorticoid production, or cause other adverse effects in nursing infants. Use with caution.

Pediatric Use

Efficacy and safety of corticosteroids in pediatric patients are based on the well-established course of effect of corticosteroids. Adverse effects of corticosteroids in pediatric patients are similar to those in adults.

Published studies provide evidence of efficacy and safety in pediatric patients for treatment of nephrotic syndrome (>2 years of age), and aggressive lymphomas and leukemias (>1 month of age). Other indications for pediatric use of corticosteroids (e.g., severe asthma) are based on adequate and well-controlled trials conducted in adults.

Carefully observe pediatric patients with frequent measurements of BP, weight, height, intraocular pressure, and clinical evaluation for infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Pediatric patients who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in growth velocity.

Geriatric Use

With prolonged therapy, muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones may occur. May be especially serious in geriatric or debilitated patients.

Before initiating glucocorticoid therapy in postmenopausal women, consider that such women are especially prone to osteoporosis.

Use with caution in patients with osteoporosis.

Hepatic Impairment

Patients with cirrhosis show an exaggerated response to glucocorticoids.

Renal Impairment

Use with caution.

Common Adverse Effects

Associated with long-term therapy: Bone loss, cataracts, indigestion, muscle weakness, back pain, bruising, oral candidiasis.

General

• Route of administration and dosage depend on the condition being treated and the patient response.

Alternate-day Therapy

• Alternate-day therapy in which a single dose (twice the usual daily dosage) is administered every other morning is the dosage regimen of choice for long-term oral glucocorticoid treatment of most conditions. This regimen provides relief of symptoms while minimizing adrenal suppression, protein catabolism, and other adverse effects.

• If alternate-day therapy is preferred, only use a “short-acting” glucocorticoid that suppresses the HPA axis <1.5 days after a single oral dose (e.g., prednisone, prednisolone, methylprednisolone).

• Some conditions (e.g., rheumatoid arthritis, ulcerative colitis) require daily glucocorticoid therapy because symptoms of the underlying disease cannot be controlled by alternate-day therapy.

Discontinuance of Therapy

• A steroid withdrawal syndrome consisting of lethargy, fever, myalgia can develop following abrupt discontinuance. Symptoms often occur without evidence of adrenal insufficiency (while plasma glucocorticoid concentrations were still high but were falling rapidly).

• If used for only brief periods (a few days) in emergency situations, may reduce and discontinue dosage quite rapidly.

• Very gradually withdraw systemic glucocorticoids until recovery of HPA-axis function occurs following long-term therapy with pharmacologic dosages. (See Adrenocortical Insufficiency under Warnings.)

• Exercise caution when transferring from systemic glucocorticoid to oral or nasal inhalation corticosteroid therapy.

• Many methods of slow withdrawal or “tapering” have been described.

• In 1 suggested regimen, decrease by 2.5–5 mg every 3–7 days until the physiologic dose (5 mg) is reached.

• Other recommendations state that decrements usually should not exceed 2.5 mg every 1–2 weeks.

• When a physiologic dosage has been reached, single 20-mg oral morning doses of hydrocortisone can be substituted for whatever glucocorticoid the patient has been receiving. After 2–4 weeks, may decrease hydrocortisone dosage by 2.5 mg every week until a single morning dosage of 10 mg daily is reached.

• For certain acute allergic conditions (e.g., contact dermatitis such as poison ivy) or acute exacerbations of chronic allergic conditions, glucocorticoids may be administered short term (e.g., for 6 days). Administer a high dose on the first day of therapy, then withdraw therapy by tapering the dosage over several days.

Administration

Oral Administration

Administer orally as tablets, syrup, or oral solution.

Dosage

Dosage of prednisolone sodium phosphate is expressed in terms of prednisolone.

After a satisfactory response is obtained, decrease dosage in small decrements to the lowest level that maintains an adequate clinical response, and discontinue the drug as soon as possible.

Monitor patients continually for signs that indicate dosage adjustment is necessary, such as remissions or exacerbations of the disease and stress (surgery, infection, trauma).

High dosages may be required for acute situations of certain rheumatic disorders and collagen diseases. After a response has been obtained, drug often must be continued for long periods at low dosage.

High or massive dosages may be required in the treatment of pemphigus, exfoliative dermatitis, bullous dermatitis herpetiformis, severe erythema multiforme, or mycosis fungoides. Early initiation of systemic glucocorticoid therapy may be life-saving in pemphigus vulgaris. Reduce dosage gradually to the lowest effective level, but discontinuance may not be possible.

Pediatric Patients

Base pediatric dosage on severity of the disease and patient response rather than on strict adherence to dosage indicated by age, body weight, or body surface area.

Usual Dosage

Oral

Syrup or tablets: Initially, 0.14–2 mg/kg daily or 4–60 mg/m² daily in 4 divided doses.

Oral solution: Initially, 0.14–2 mg/kg daily or 4–60 mg/m² daily in 3 or 4 divided doses.

Asthma

Oral

For the treatment of refractory bronchial asthma and related bronchospasm (severe persistent asthma) not controlled with high maintenance dosages of an inhaled corticosteroid and a long-acting bronchodilator, add an oral corticosteroid (e.g., prednisone, prednisolone, methylprednisolone) at a dosage of 1–2 mg/kg daily in single or divided doses. Continue a short course of oral corticosteroid therapy (usually 3–10 days) until a peak expiratory flow rate of 80% of personal best is achieved or until symptoms resolve. May need a longer duration of treatment in some children. No evidence that tapering the dosage after improvement will prevent relapse.

Nephrotic Syndrome

Oral

Usual dosage: 60 mg/m² given in 3 divided doses for 4 weeks, followed by 4 weeks of alternate-day therapy at single doses of 40 mg/m².

Adults

Usual Dosage

Oral

Initially, 5–60 mg daily, depending on the disease being treated; usually administered in 2–4 divided doses.

Acute Exacerbations of Multiple Sclerosis

Oral

Usual dosage: 200 mg daily for 1 week, followed by 80 mg every other day for a month.

Metabolized by CYP3A4.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (decreased prednisolone metabolism).

Inducers of CYP3A4: Potential pharmacokinetic interaction (enhanced metabolism of prednisolone).

Specific Drugs and Laboratory Tests