Project TitleCorticosteroids & Associated Diseases

A research presented by

Student name: Mohammad khraisStudent No: 9750079

Project supervisor Dr.Rafiq R. A. Abou-Shaaban

Jan.2001

Ajman University for Science and TechnologyAbu Dhabi Branch

UAE

Research for this project was carried out by me during the period of Hospital Pharmacy Training-1 no.700315(academic year 2000-2001)

Signed Date Jan 10th 2000

ACKNOWLEDGMENTS

Sincere gratitude were extended to Dr. Rafeeq Abu Shaaban from the

pharmaceutical department, to the support, encouragement and fruitful

accompaniment through out the training and presentation of this

project.

The author is indebted to project supervisor Dr Asim Ahmed, for the

continuous follow up , constructive criticism , and valuable comments.

The author wishes to express special gratitude and thanks to those

contributing in this revolutionary, distinctive and advanced Hospital

Pharmacy training 1; namely Dr.Danna Sallam and the staff of the New

Medical Center Hospital.

Finally the author wishes to express heartfelt thanks to Dr. Abduelmula in-

Charge of the Central training committee for furnishing the entire Clinical

Pharmacy Services as far as this term is concerned.

INDEX

Description

Section l 1.0 Introduction to corticosteroids1.1 Unlabeled uses of corticosteroids1.2 Pharmacokinetics of corticosteroids1.3 Classification of corticosteroids1.4 Availability of corticosteroids

Section II 2.0 Adverse effects of corticosteroids2.1 Treatment of adverse effects2.2 Withdrawal of corticosteroids

Section III3.0Uses and administration of corticosteroids3.1 Routes of administration of corticosteroids3.2 Disorders in which corticosteroids are administered

Section IV4.0 Precautions for corticosteroids 4.1 Drug interactions

Section V5.0 Absorption and fate of corticosteriods

Section VI6.0 Antagonists of adrenocortical agents6.1 Synthesis inhibitors & glucocorticoid antagonists6.2 Mineralocorticoid antagonists

Section VII7.0 Topical corticosteroids7.1 Properties of topical steroid7.2 Guidance for the use of topical corticosteroids

Section VIII8.0 Corticosteroids for ophthalmic uses8.1 Classes of corticosteroids used in eye disorders

Section IX9.0 Drugs names and properties

Section XThe indications, contra-indications, warnings, precautions…etc, of each class of the corticosteroids10.0 Glucocorticoids10.1 Mineralocorticoids

ReferencesBasic and clinical pharmacology (Bertram G. Katzung)Martindale the extra pharmacopoeia (30th addition)Clinical drug data Clinesphere

Section I: Introduction1.0 Introduction toCorticosteroids

Corticosteroids are used for the replacement therapy in adrenal insufficiency and are also given for their palliative anti-inflammatory and immunosuppressant effects in a wide variety of disorders. High doses may be needed for emergencies but in general the lowest effective dose should be given for the shortest possible time; local administration is preferable. Withdrawal of systemic treatment should be gradual since abrupt cessation of corticosteroids may precipitate acute adrenal insufficiency. To prevent adrenal insufficiency resulting from increased corticosteroids requirements during periods of stress or trauma, it may be necessary to increase the dose. Adverse effects of corticosteroids mainly result from an excessive action on electrolyte balance, metabolism and tissue repair, and an inhibitory effect on secretion of corticotrophin (leading to adrenal insufficiency). Susceptibility to all kinds of infection may be increased and there may be growth retardation in children.The adrenal cortex produces a number of steroids, which may be divided into 3 classes; glucocorticoids, mineralocorticoid, and sex corticoids that include mainly androgens. The glucocorticoids (cortisone and hydrocortisone or cortisol) principal pharmacological actions are upon gluconeogenesis, glycogen deposition, and protein, lipid, and calcium metabolism, together with inhibition of corticotrophin secretion, anti-inflammatory activity, and effects on tissue repair, the heart, kidneys, and CNS. The principal actions of the mineralcorticoids (deoxycortone and aldosterone) are upon electrolyte and water metabolism.Glucocorticoids and mineralcorticoids are collectively known as corticosteroids and apart from aldosterone, the endogenous corticosteroids (cortisone, deoxycortone, and hydrocortisone) are secreted under the influence of the interior pituitary hormone, corticotrophin. All 4 naturally occurring corticosteroids have mineralocorticoid actions to a varying degree and they all, with possible exception of deoxycortone, have some glucocrticoid actions.In addition to the naturally occurring corticosteroids, many synthetic steroids with similar properties have been introduced. In developing these synthetic analogues the aim has usually been firstly to produce enhanced potency generally and secondly to separate the 2 main pharmacological actions so that, for example, an increase in glucocorticoid actions is not accompanied by a parallel increase in the mineralocorticoid effects.It appears that a measure of corticosteroids potency as a glucocorticoid is the degree of inhibition of corticotrophin secretion it produces.The chemical structures of the corticosteroids are very similar to each other.The main corticosteroids used systemically are hydroxy compounds (alcohol). They are relatively insoluble in water and the sodium salt of the phosphate or succinate ester is generally used to provide water-soluble forms for the injections or solutions. Such esters are readily hydrolyzed in the body.Esterification of corticosteroids at the 17 or 21 positions with fatty acids generally increases the activity on the skin. The formation of cyclic acetonides at the 16 and 17

positions further increases topical anti-inflammatory activity, usually without increasing systemic glucocorticoid activity, and fluorinated corticosteroids also generally have increased topical activity. Some corticosteroids esterified at the 17 position are much more potent topically than systemically, e.g. beclomethasone dipropionate and betamethasone valerate; they are used by inhalation where their potent anti-inflammatory effect on the lungs has little systemic effect.In the medical and pharmacological the name of unesterified corticosteroids have frequently been used for both the unesterified and esterified forms and it is not always apparent to which form is being made. The unesterified form is sometimes qualified by the phrase ‘free alcohol’.

1.1 Unlabeled uses of corticosteroids :

Use Drug/Comment

Acute mountain sickness Dexamethasone 4 mg q 6 h; prevention or treatment

Antiemetic Dexamethasone most common, 16 to 20 mgBacterial meningitis Dexamethasone 0.15 mg/kg q 6 h; to decrease incidence of

hearing lossBronchopulmonary dysplasia in preterm infants

Dexamethasone 0.5 mg/kg, then taper.

COPD Prednisone 30 to 60 mg/day for 1 to 2 weeks, then taperDepression Diagnosis of Dexamethasone 1 mgDuchenne's muscular dystrophy Prednisone 0.75 to 1.5 mg/kg/day; to improve strength and

function

Graves ophthalmopathy Prednisone 60 mg/day, taper to 20 mg/dayHepatitis, severe alcoholic Methylprednisolone 32 mg/day; to reduce mortality

Hirsutism Dexamethasone 0.5 to 1 mg/dayRespiratory distress syndrome Prevention in premature neonates (beta methasone most

common); adults, methylprednisolone 30 mg/ kg (controversial)

Septic shock Methylprednisolone 30 mg/kg IV most common (very controversial)

Spinal cord injury Acute Methylprednisolone IV within 8 hrs of injury; to improve neurologic function

Tuberculosis pleurisy Prednisolone 0.75 mg/kg/day, then taper; concurrently with antituberculous therapy

1.2 Pharmacokinetics of corticosteroids:

The major glucocorticoid in humans is cortisol. It is synthesized from cholesterol by the cells of the zona fasciculata and zona reticularis and released into the circulation under the influence of ACTH. In the normal adult in the absence of stress, 10-20mg of cortisol is secreted daily. The rate of secretion changes in a circadian rhythm governed by irregular pulses of ACTH that peak in the early morning hours and after meals and that are also influenced by light. In plasma, cortisol is bound to plasma protiens. Corticosteroids-binding globulin (CBG), an α2-globulin synthesized by the liver, binds 75% of the circulating hormone under normal circumstances. The remainder is free (about 20%) or loosely bound to albumin (about 5%) and is available to exert its effect on target cells. When plasma cortisol levels exceed 20-30 μg/dL, CBG is saturated, and the concentration of free cortisol rises rapidly. CBGis increased in pregnancy and with estrogen adminstration, which increases its synthesis by the liver, and in hyperthyroidism. It is decreased by hypothyroidism, genetic defects in synthesis, and protien deficiencystates. Albumin has a large capacity but low affinityfor corisol. Synthetic corticosteroids such as dexamethasone are largely bound to albumin.The half-life of cortisol in the circulation is normally about 60-90 minutes; half-life may be increased when hydrocortisone (the pharmaceutical preparations of cortisol) is administered in large amounts or when stress, hypothyroidism, or liver disease is present. Only 1% of cortisol is converted to cortisone by 11-hydroxysteroid dehydrogenase in the kidney and other tissues with mineralocorticoid receptors before reaching the liver. Most of the cortisone and the remaining cortisone and the remaining cortisol is inactivated in the liver by reduction of the 4,5 double bond in the A ring and subsequent conversion to tetrahydrocortisol and tetrahydrcortisone by 3-hydroxysteroid dehydrogenase.

1.3 Classification of corticosteroids:

Very potent potent Moderatly potent Mild

clobetasol propionate 0.05% amcinonide 0.1% alcometasone dipropionate 0.05% fluocinolone acetonide 0.0025%

diflcortolone valerate 0.3% beclomethasone dipropionate betamthasone valerate 0.025% Hydrocortisone 0.5 and 1%

flucinolone acetonide 0.2% betamethasone benzoate 0.025% clobetasone butyrate 0.05% Hydrocortisone acetate 1%

halcinonide 0.1% betamethasone valerate 0.1% desoxymethasone 0.05% methylprednisolone acetate0.25%

budesonide 0.025% flumethasone pivalate 0.02%

desonide 0.05% flucinolone acetonide 0.01%

desoxymethasone 0.25% and 0.00625%

doflorasone diacetate 0.05% fluocortin butyl 0.75%

difucortolone valerate 0.1% fluocortolone preparations

fluclorolone acetonide 0.025%

fluocinolone acetonide 0.025%

fluocinoide 0.05%

fluprednidene acetate 0.1%

Hydrocortisone butyrate 0.1%

mometasone furoate 0.1%

trimcinolone acetonide 0.1%

Glucocorticoid Approximate equivalent dose (mg)

Relative anti-inflammatory (glucocorticoid) potency

Relative mineralocorticoid potency

Half-lifePlasma (min)

Half-life biological (hrs)

Type of the glucocorticoid

Cortisone 25 0.8 2 30 12-8 Short acting

Hydrocortisone 20 1 2 118-80 12-8 Short acting

Prednisone 5 4 1 60 36-18 Intermediate

actingPrednisolone 5 4 1 212-115 36-18 Intermediate

acting

Triamcinolone 4 5 0 +200 36-18 Intermediate acting

Methylprednisolone 4 5 0 188-78 36-18 Intermediate acting

Dexamethasone 0.75 30-20 0 210-110 54-36 Long acting

Betamethasone 0.75-0.6 30-20 0 +300 54-36 Long acting

1.4 Availability of corticosteroids.

Section II: Adverse reactions2.0Adverse effects of corticosteroidsThe side-effects associated with the use of corticosteroids in the large doses often necessary to produce a therapeutic response result from excessive action on electrolyte balance, excessive action on other aspects of metabolism including gluconeogenesis, the

action on tissue repair and healing, and an inhibitory effect on the secretion of corticotrophin by the anterior lobe of the pituitary gland.Disturbance of the electrolyte balance is manifest in the retention of sodium and water, with edema and hypertension, and in the increased excretion of potassium with the possibility of hypokalaemic alkalosis. In susceptible patients, cardiac failure may be induced. Disturbances of electrolyte balance are common with the naturally occurring corticosteroids, such as cortisone, deoxycortone, and hydrocortisone, but are less frequent with many synthetic derivatives, such as betamethasone, dexamethasone, methylprednisolone, prednisolone, prednisone, and triamcinolone, which have little or no mineralocorticoid activity.Other excessive metabolic effects lead to mobilization of calcium and phosphorus, with osteoporosis and spontaneous fractures, nitrogen depletion, and hyperglycemia with accentuation or precipitation of the diabetic state. The insulin requirements of diabetic patients are increased. Increased appetite is often reported.The effect on tissue repair is manifest in delayed wound healing, and increased liability to infection; infections may also be masked since corticosteroids have marked anti-inflammatory properties with analgesic and antipyretic effects. Increased susceptibility to all kinds of infection, including sepsis, tuberculosis, fungal infections, and viral infections, has been reported in patients on corticosteroids therapy; for example, Candida infections of the mouth in patients treated with corticosteroids, especially if these are given concomitantly with antibiotics, are not uncommon.The dose of corticosteroid required to diminish corticotrophin secretion with consequent atrophy of the adrenal cortex and the time required for its occurrence vary from patient to patient. Acute adrenal insufficiency may occur during prolonged treatment or on cessation of treatment and may be precipitated by stressful situations, for example, infection or trauma. Growth retardation in children has been reported. High doses of corticosteroids administered during pregnancy may cause foetal or neonatal adrenal suppression.Large doses of corticosteroids, or of corticotrophin, may produce Cushingoid symptoms typical of hyperactivity of the adrenal cortex, with moon-face, sometimes with hairsutism, buffalo hump, flushing, increased bruising, ecchymoses, atriae, and acne, sometimes leading to a fully developed Cushing’s syndrome. If administration is discontinued these symptoms are usually reversed, but sudden cessation is dangerous. Rapid intravenous administration of large doses of corticosteroids may cause cardiovascular collapse.Other adverse effect include amenorrhoea, hyperhidrosis, skin thinning, mental and neurological disturbances, intracranial hypertension, acute pancreatitis, and aseptic necrosis of bone. An increase in the coagulability of the blood may lead to thrombo-embolic complications. Peptic ulceration has been reviews do not always agree that corticosteroids are responsible for an increased incidence. Muscle weakness and wasting occur occasionally, particularly when corticosteroids are taken in large doses. The former arises from the mineralcorticoid properties of corticosteroids, the latter from their glucocorticoid properties and is most evident with triamcinolone. Adverse effects of corticosteroids appear equally with all types of preparations, and vary with the different strength of each preparation. Short courses at high doses for emergencies appear to cause less side effects than prolonged courses with lower doses.

Most topically applied corticosteroids may, under certain circumstances, be absorbed in sufficient amounts to produce systemic effects. The topical application of corticosteroid preparations to the eyes has produced corneal ulcers, raised intra-ocular pressure, and reduces visual function, and systemic administration has caused posterior subcapsular cataract. Application of corticosteroids to the skin has led to loss of skin collagen and subcutaneous atrophy; local hypopigmentation of deeply pigmented skins has been reported following both the intradermal injection and topical application of potent corticosteroids.

1. Adrenal suppression 2. Effects on bones and joints3. Effects on carbohydrates metabolism4. Effects on cardiovascular system5. Effects on the cerebrovascular system6. Effects on the eyes7. Effects on the gastro-intestinal tract8. Effects on the growth9. Effects on lipid metabolism10. Effects on the mental state11. Effects on the nervous system12. Effects on the pancreas13. Effects on the skin 14. Effects on the voice15. Hypersensitivity and anaphylaxis16. Pregnancy and neonate 17. Tumor lysis syndrome

2.1 Treatment of adverse effects of corticosteroids

The adverse effects of corticosteroids are nearly always due to their use in excess of normal physiological requirements. They should be treated symptomatically, where possible the dosage being reduced or the drug slowly withdrawn.The treatment of acute adrenal insufficiency in corticosteroid-treated patients, whether it be due to accidental abrupt withdrawal of the corticosteroid or the inability of the patient’s adrenals to cope with the increases stress of infection or accidental or surgical trauma.

2.2 Withdrawal of corticosteroids

The use pharmacological doses of corticosteriods to treat disease suppresses the endogenous secretion of corticotrophin by the anterior pituitary, with the result that the adrenal cortex becomes atrophied. Sudden withdrawal or reduction in dosage, or an

increase in corticosteroids requirements associated with the stress of infection or accidental or surgical trauma, may then precipitate acute adrenal insufficiency. Symptoms of adrenal insufficiency include malaise, muscle weakness, mental changes, muscle and joint pain, desquamation of the skin, dyspnoea, anaroxia, nausea, vomiting, fever, hypoglycaemia, hypotension, and dehydration; deaths have followed the abrupt withdrawal of corticosteroids.Other effects that may occur during withdrawal or change of corticosteroids therapy include benign intracranial hypertension with headache and vomiting and papilloedema caused by cerebral edema. Latent rhinitis or eczema may be unmasked.Duration of treatment and dosage appear to be important factors in determining suppression of the pituitary-adrenal response to stress on cessation of corticosteroid treatment, and individual liability to suppression is also important.Corticosteroids withdrawal should therefore always be gradual, the rate depending upon individual patient’s response, the dose, the disease being treated, and the duration of therapy. Recommendations for initial reduction vary according to different steps.Adrenal function should be monitored throughout the withdrawal period. The gradual withdrawal of corticsteroids therapy permits a return of adrenal function adequate for daily needs, but a further one to two years may be required for the return of function necessary to meet the stress of infection, surgical operations, or trauma. On such occasions patients with a history of recent corticosteroid withdrawal should be protected by means of supplementary corticosteroid therapy.

Section III: Uses of corticosteroids3.0Uses and adminstration of corticosteroids The corticosteroids are used in physiological doses for replacment therapy in adrenal insufficiency. Pharmacological doses are used when palliative anti-inflammatory or immunosuppressant effects are required. Before instituting therapy the benefits and risks

of corticosteroids should be considered; where appropriate, local rather than systemic therapy should be used for the shortest possible duration of time; high doses may be neede for life-threatening situations.In primary adrenal insufficiency, such as Addison's disease or after adrenalectomy, both mineralocorticoid and glucocorticoid replacementis needed; hydrocortisone is generally given by mouth together with fludrocortisone.In secondary adrenal insufficiency, associated with inadequate coticotrophin secretion, glucocorticoid replacement alone is adequate. The emergancy treatment of adrenal insufficiency usually involves the intravenous adminstration of hydrocortisone sodium succinate or another suitable synthetic corticosteroids, together with infusions of sodium chloride and glucose to correct electrolyte disturbances. The anti-inflammatory and immunosuppressant glucocorticoid properties of corticosteroids are used to suppress manifestations of disease in a wide range of disorders. For these purposes, the synthetic analogues with enhanced glucorticoid properties linked with enhanced glucocorticoid properties, are preferred to cortisone and hydrocortisone. Despite the existance of very powerful synthetic glucocorticoids with virtually no mineralcorticoid activity, the hazards of inappropriately high glucocorticoid therapy are such that the less powerful prednisolone and prednisone are the glucorticoids of choice for most conditions, since they allow for a greater margin of safety. There is a little to choose between prednisolone and prednisone; prednisolone may be preferred since, like hydrocortisone, it exists in a metabolically active form, whereas prednisone, like cortisone, is inactive and must be converted into its active form by the liver; hence, particularly in some liver disorders, prednisone's bioavailability is less reliable.Doses of corticosteroids higher than those required for physiological replacement will eventually lead to some degree of adrenal suppression, the extent depending on the dose given, and the route, frequency, time, and duration of administration. The adrenal glands have a daily output equivalent to approximatly 20mg of hydrocortisone (cortisol), but individual blood-cortisol concentrations may vary widely, and can increase up to ten-fold or more during stress. Therefore, during periods of stress, such as during and when suffering from intercurrent infections, the corticosteroid dosage of patients must be increased. Intramuscular or intravenous injection of hydrocortisone 100mg (usually as the sodium succinate) with the premedication and repeated every 8 hours has been used in patients on long-term corticosteroid therapy undergoing minor surgical procedures. This dose is generally tapered off 5 days to reach a typical maintenancedose of 20 to 30mg daily. Some studies, however, have suggested that such routine supplementation may not always be necessary and that in some patients only postoperative supplements need to be given when clinical symptoms of insufficiency arise.

3.1Routes of administration of corticosteroids:1. Oral therapy 2. Parentral therapy3. Intr-articular injection4. Topical application5. intralesional injection

6. Opthalmic preparations7. Ear drops8. Inhalational therapy9. Rectal adminstration

3.2 Disorders in which corticosteroids are administered:Administration in kidney failureAdministration in liver failureAdrenal insufficiencyAIDSAnaphilactic shockAspiration syndromesBehcet's syndromeBites and stingsBlood disordersBone disordersCerebral oedemaCogan's syndromeCongenital adrenal hyperplasiaConnective tissue disordersEpilepsyEye disordersGastro-intestinal disordersHypercalcaemiaInfections: Eye infections Leishmaniasis Leprosy Meningitis Pneumocystis Carini Pneumonia Septic shock Tuberculosis Viral encephalitisKawasaki diseaseOrgan and tissue transplantationKidney disordersPainPancreatitisPregnancy and neonateRespiratory disordersRheumatoid disease and osteoarthritisRhinitisSarcoidosisSkin disordersSpinal cord injuryThyroid disorders

Vascular disorders

Some therapeutic indications for the use of glucocorticoids in nonadrenal disorders

Disorder Examples

Allergic reactionsAngioneurotic edema, asthma, bee sting, contact dermatitis, drug reactions, allergic rhinitis, urticaria, serum sickness

Collagen-vascular disorderGiant cell arteritis, lupus erythematosus, mixed connective tissue syndrome,polymyalgia rheumatica, rheumatoid arthritis

Eye disease Acute uveitis, allergic conjunctivitis, choroiditis, optic neuritisGastrointestinal disease Inflammatory bowel disease, nontropical sprue, subacutal hepatic necrosis

Hematologic disorderAcquired and autoimmune hemolytic anemia, allergic purpura, leukaemia, idiopathic thrombocytopenic purpura, multiple myeloma

Infections Gram-negative septicemia; occasionally helpful to suppress excessive inflammationInflammatory conditions of bones and joints Arthritis, bursitis, tenosynovitis

Neurologic disorder Cerebral edema (large doses of dexamethasone are given after brain surgery), multiple sclerosis

Organ transplants Prevention and treatment of rejection (immunosuppression)Pulmonary diseases Aspiration pneumonia, asthma, prevention of infant respiratory distress syndrome, sarcoidosisRenal disorder Nephrotic syndrome

Skin diseases Atopic dermatitis, dermatoses, lichen simplex chrnicus, mycosis fungoides, pemphigus, seborrheic dermatitis, xerosis

Thyroid diseases Malignant exophthalmos, sub acute thyroiditis

Miscellaneous Hypocalcaemia, mountain sickness

Section IV: Precautions and interactions4.0 Precautions for corticosteroidsUnless considered life-saving, systemic administration of corticosteroids is contra-indicated in patients with peptic ulcer, osteoporosis, psychoses, or severe psychoneuroses, and they should be used only with great caution in the presence of congestive heart failure or hypertension, in patients with diabetes mellitus, epilepsy, glaucoma, infectious diseases, ocular herpes simplex, chronic renal failure and ureamia,

and in elderly persons. Patients with active or doubtfully quiescent tuberculosis should not be given corticosteroids except, very rarely, as adjuncts to treatment with antitubercular drugs, patients with quiescent tuberculosis should be observed closely and should receive chemoprophylaxis if corticosteroid therapy is prolonged.Corticosteroids are usually contra-indicated in the presence of acute infections, because of interference with inflammatory and immunological response. Similarly, patients already receiving corticosteroid are more susceptible to infection, the symptoms of which, moreover, may be masked until an advanced stage has been reached. Because of the risk of precipitating a serious infection, live vaccines should not be given to patients receiving high-dose systemic corticosteroid therapy; killed vaccines or toxoids may be given although the response may be attenuated. Children are at special risk of infection and may require prophylaxis with immunoglobulin.During long courses of corticosteroid therapy, patients should be examined regularly and checked for hypertension, glycosuria, hypokalaemia, gastric discomfort, and mental changes. Sodium intake may need to be reduced and potassium supplements may be necessary. Monitoring of the fluid intake and output, and daily weight records may give early warning of fluid retention. Back pain may signify osteoporosis. Children are at special risk from raised intracranial pressure. Infections should be treated as an emergency. Patients should carry cards (and preferably also wear bracelets) giving full details of their corticosteroid therapy; they and their relatives should be fully conversant with the implications of their therapy and the precautions to be taken.Measures to compensate for the adrenals’ inability to respond to stress include increasing the dose to cover minor intercurrent illnesses or trauma such as surgery (with intramuscular administration to cover vomiting).Rapid intravenous injection of massive doses of corticosteroids may sometimes cause cardiovascular collapse and injections should therefore be given slowly or by infusions. High doses should not be used for prolonged treatment. Concurrent administration of barbiturates, carbamazepine, phenytoin, or rifampicin may enhance the metabolism and reduce the effects of corticosteroids. Concurrent administration of corticosteroids with potassium-depleting diuretics, such as thiazides or frusemide, may cause excessive potassium loss. There may be an increased incidence of gastro-intestinal bleeding and ulceration when corticosteroids are given with non-steroidal anti-inflammatory agents. Response to anticoagulants may be altered by corticosteroids and requirements of antidiabetics and antihypertensives may be increased. Corticosteroids may decrease serum concentrations of salicylates and may decrease the effect of antimuscarinics in myasthenia gravis.Many drugs have been reported to interfere with certain assay procedures for corticosteroids themselves may interfere with or alter the results of assays for some endogenous substances or drugs.Topical applications of corticosteroids should not be made with an occlusive dressing to large areas of the body because of the increased risk of systemic toxicity and should not, in general, be used in the presence of infection. They should not be used for the treatment of rosacea and should not be used indiscriminately for pruritus. Occasionally they may be used with the addition of a suitable antimicrobial substance in the treatment of infected skin but there is a risk of sensitivity reactions occurring. Corticosteroids should not be

applied to ulcers of the leg and long-term topical use is best avoided, especially in children.Caution is required when corticosteroids are used locally in the treat eye disorders.

4.1 Drug Interactions : Corticosteroid Drug Interactions

Precipitant drug Object drug DescriptionAminoglutethimide Dexamethasone Possible loss of dexamethasone-induced

adrenal suppression.Barbiturates Corticosteroids Decreased pharmacological effects of the

corticosteroid may be observed.Cholestyramine Hydrocortisone The hydrocortisone AUC may be

decreased.Oral Contraceptives Corticosteroids Corticosteroid half-life and concentration

may be increased and clearance decreased.

Ephedrine Dexamethasone A decreased half-life and increased clearance of dexamethasone may occur.

Estrogens Corticosteroids Corticosteroid clearance may be decreased.

Hydantoins Corticosteroids Corticosteroid clearance may be increased, resulting in reduced therapeutic effects.

Ketoconazole Corticosteroids Corticosteroid clearance may be decreased and the AUC increased.

Macrolide antibiotics Methylprednisolone Significant decrease in methylprednisolone clearance has been used to decrease methylprednisolone dose.

Rifampin Corticosteroids Corticosteroid clearance may be increased resulting in decreased therapeutic effects.

Anticholinesterases Corticosteroids Anticholinesterase effects may be antagonized in myasthenia gravis.

Oral anticoagulants Corticosteroids Anticoagulant dose requirements may be reduced. Conversely, corticosteroids may oppose the anticoagulant action.

Cyclosporine Corticosteroids Although this combination is therapeutically beneficial for organ transplants, toxicity may be enhanced.

Digitalis glycosides Corticosteroids Coadministration may enhance the possibility of digitalis toxicity associated with hypokalemia.

Isoniazid Corticosteroids Isoniazid serum concentrations may be decreased.

Nondepolarizing muscle relaxants

Corticosteroids Corticosteroids may potentiate, counteract or have no effect on the neuromuscular blocking action.

Potassium-depleting agents (e.g. diuretics)

Corticosteroids Observe patients for hypokalemia.

Salicylates Corticosteroids Corticosteroids will reduce serum salicylate levels and may decrease their effectiveness.

Somatrem Corticosteroids Growth-promoting effect of somatrem may be inhibited.

Theophyllines Corticosteroids Alterations in the pharmacological activity of either agent may occur.

Section V: Absorption and fateAbsorption and fate of corticosteroidsCorticosteroids are in general, readily absorbed from the gastro-intestinal tract. They are also well absorbed from sites of local application. When administered by topical application, particularly under an occlusive dressing or when the skin is broken, or as a pulmonary aerosol inhalation or a rectal enema, sufficient corticosteroid may be absorbed to give systemic effects. Water-soluble forms of corticosteroids are given by intravenous injection for a rapid response; more prolonged effects are achieved using lipid-soluble forms of corticosteroids by intramuscular injection.Corticosteroids are rapidly distributed to all body tissues. They cross the placenta and may be excreted in small amounts in breast milk.Most corticosteroids in the circulations are extensively bound to plasma proteins, mainly to globulin and less so to albumin. The corticosteroid-binding globulin has high affinity but low binding capacity, while the albumin has low affinity but large binding capacity. The synthetic corticosteroids are less extensively protein bound than hydrocortisone (cortisol). They also tend to have longer half-lives.Corticosteroids are metabolized mainly in the liver but also in the kidney, and are excreted in the urine. The slower metabolism of the synthetic corticosteroids with their lower protein-binding affinity may account for their increased potency compared with the natural corticosteroids.

Section VI: corticosteroids antagonist 6.0 Antagonists of adrenocortical agents

6.1 Synthesis inhibitors & glucocorticoid antagonists

1. MetyraponeMetyrapone is a relatively selective inhibitor of steroid synthesis.Mechanism of action: It inhibits 11-hydroxylation, interfering with cortisol and corticosterone synthesis and leading to secretion of 11-deoxycortisol. In the presence of a normal pituitary gland, there is a compensatory increase in 11-deoxycortisol production. This response is adapted for clinical use as a diagnostic test for the pituitary gland. Adverse reactions:The drug doses produce transient dizziness and gastrointestinal disturbances. The major adverse effects observed are salt and water retention and hairsutism.Indications:This agent has not been widely used in Cushing’s syndrome. However, in doses of 0.25 g twice daily to 1 g four times daily, metyrapone can reduce cortisol production to normal levels in some patients with adrenal tumor, ectopic ACTH syndromes, and hyperplasia. It may be useful in the management of severe manifestations of cortisol excess while the cause is being determined or in conjunction with radiation or surgical treatment. Metyrapone most commonly used in tests of adrenal function.Biopharmaceutics of metyrapone:The blood levels of 11-deoxycortisol and the urinary excretion of 17-hydroxycorticoids are measured before and after administration of the compound. Normally, there is a twofold or greater increase in the urinary 17-hydroxycorticoid excretion.

2. AminoglutethimideAminoglutethimide blocks the conversion of cholesterol to pregnenolone and causes a reduction in the synthesis of all hormonally active steroids. It has been used in the conjunction with dexamethasone or hydrocortisone to reduce or eliminate estrogen and androgen production in patients with carcinoma of the breast. In a dosage of 1 g/d it was well tolerated; however, with higher dosage, lethargy was a common effect. This drug can be used in conjunction with ketoconazole to reduce steroid secretion in patients with Cushing’s syndrome due to adrenocortical cancer that does not respond to mitotane.Aminoglutethimide also apparently increases the clearance of some steroids. It has been shown to enhance the metabolism of dexamethasone, reducing its half-life from 264 minutes to 120 minutes.Indications: Cushing's syndrome: For the suppression of adrenal function in selected patients with

Cushing's syndrome. Unlabeled uses: Aminoglutethimide has been used successfully in postmenopausal

patients with advanced breast carcinoma and in patients with metastatic prostate carcinoma.

Aminoglutethimide was previously marketed as an anticonvulsant, but was withdrawn for that use in 1966.

Drugs proprietary nameCytadren (Ciba) 250 mg tablets (Ciba 24). White, scored tablets in 100 tabs box.

Administration and Dosage: Institute treatment in a hospital until a stable dosage regimen is achieved. Give 250 mg 4 times daily, preferably at 6 hour intervals. Follow adrenal cortical

response by careful monitoring of plasma cortisol until the desired level of suppression is achieved. If cortisol suppression is inadequate, dosage may be increased in increments of 250 mg daily at intervals of 1 to 2 weeks to a total daily dose of 2 g.

Dose reduction or temporary discontinuation may be required in the event of adverse responses (ie, extreme drowsiness, severe skin rash or excessively low cortisol levels). If skin rash persists for > 5 to 8 days or becomes severe, discontinue the drug. It may be possible to reinstate therapy at a lower dosage following the disappearance of a mild or moderate rash.

Mineralocorticoid replacement therapy (ie, fludrocortisone) may be necessary. If glucocorticoid replacement therapy is needed, 20 to 30 mg hydrocortisone orally in the morning will replace endogenous secretion.

Actions: Pharmacology: Aminoglutethimide inhibits the enzymatic conversion of cholesterol

to d5–pregnenolone, thereby reducing the synthesis of adrenal glucocorticoids, mineralocorticoids, estrogens and androgens. Aminoglutethimide blocks several other steps in steroid synthesis, including the hydroxylations required for the aromatization of androgens to estrogens. A decrease in adrenal secretion of cortisol is followed by an increased secretion of pituitary adrenocorticotropic hormone (ACTH), which will overcome the blockade of adrenocortical steroid synthesis by aminoglutethimide.

Pharmacokinetics: Aminoglutethimide is effectively absorbed orally and is minimally bound to plasma protein. Its half-life is 11 to 16 hours initially, but decreases after 1 to 2 weeks to 5 to 9 hours. Approximately 34% to 54% is excreted unchanged in the urine and 20% to 50% is excreted as the acetylated metabolite (less than one-fifth as active as the parent compound). The acetylation mechanism is genetically controlled.

Clinical trials: Morning levels of plasma cortisol in patients with adrenal carcinoma and ectopic ACTH-producing tumors were reduced on the average to about one half of the pretreatment levels, and in patients with adrenal hyperplasia to about two thirds of the pretreatment levels, during 1 to 3 months of therapy with aminoglutethimide. Data available from the few patients with adrenal adenoma suggest similar reductions in plasma cortisol levels. Measurements of plasma cortisol showed reductions to >= 50% of baseline or to normal levels in one third or more of the patients studied, depending on the diagnostic groups and time of measurement.

Contraindications: Hypersensitivity to glutethimide or aminoglutethimide.Warnings: Duration of therapy: Because aminoglutethimide does not affect the underlying

disease process, it has been used primarily until more definitive therapy (ie, surgery) can be undertaken, or in cases where such therapy is not appropriate. Only a small number of patients have been treated for less than 3 months. A decreased effect or escape from a favorable effect occurs more frequently in pituitary-dependent

Cushing's syndrome, probably because of increasing ACTH levels in response to decreasing glucocorticoid levels.

Cortical hypofunction: May cause adrenal cortical hypofunction, especially under conditions of stress such as surgery, trauma or acute illness. Monitor patients carefully and give hydrocortisone and mineralocorticoid supplements as indicated. Do not use dexamethasone.

Hypotension: Aminoglutethimide may suppress aldosterone production by the adrenal cortex and may cause orthostatic or persistent hypotension. Monitor blood pressure in all patients at appropriate intervals.

Pregnancy: Category D. Aminoglutethimide can cause fetal harm when administered to pregnant women. In about 5000 patients, two cases of pseudohermaphroditism were reported in female infants whose mothers took aminoglutethimide and concomitant anticonvulsants. Normal pregnancies have also occurred during the administration of the drug. When administered to rats at doses 1/2 to 3 times the maximum human dose, aminoglutethimide caused a decrease in fetal implantation, and increased fetal deaths, teratogenic effects and pseudohermaphroditism. If this drug must be used during pregnancy, or if the patient becomes pregnant while taking the drug, apprise her of the potential hazard to the fetus.

Lactation: It is not known whether this drug is excreted in breast milk. Decide whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Children: Safety and efficacy have not been established.Precautions: Monitoring: Hypothyroidism may occur. Make appropriate clinical observations and perform

thyroid function studies as indicated. Supplementary thyroid hormone may be required.

Hematologic abnormalities have been reported. Elevations in AST, alkaline phosphatase and bilirubin have been reported. Perform appropriate clinical observations and regular laboratory studies before and during therapy. Determine serum electrolytes periodically.

Precipitant drug Object drug DescriptionAminoglutethimide Anticoagulants Anticoagulant effects may be decreased.Aminoglutethimide Dexamethasone Possible loss of dexamethasone-induced adrenal suppression.Aminoglutethimide Digitoxin Digitoxin clearance may be increased.Aminoglutethimide Medroxyprogesterone Medroxyprogesterone serum levels may be decreased.

Aminoglutethimide Theophylline The action of theophyllines may be reduced.Drug Interactions:

Aminoglutethimide Drug Interactions:

Adverse Reactions: Untoward effects have been reported in » 67% of patients treated for >= 4 weeks in

Cushing's syndrome. The most frequent effects are: Drowsiness (33%), morbilliform skin rash (17%), nausea and anorexia (12.5%). These are reversible and often disappear spontaneously within 1 or 2 weeks of continued therapy.

Cardiovascular: Hypotension, occasionally orthostatic (3%); tachycardia (2.5%). CNS: Headache and dizziness, possibly caused by decreased vascular resistance or

orthostasis (5%). Dermatologic: Rash (17%, often reversible on continued therapy); pruritus (5%).

These may be allergic or hypersensitivity reactions. Urticaria has occurred rarely. Endocrine: Adrenal insufficiency occurred during >= 4 weeks of therapy in 3% of

patients with Cushing's syndrome. Hypothyroidism, occasionally associated with thyroid enlargement, may be detected early or confirmed by measuring the plasma levels of the thyroid hormones. Masculinization and hirsutism in females and precocious sex development in males have occasionally occurred.

Hematologic: In 4 of 27 patients with adrenal carcinoma who were treated for at least 4 weeks, there were single occurrences of neutropenia, leukopenia (patient received mitotane concomitantly) and pancytopenia. One patient with adrenal hyperplasia showed decreased hemoglobin and hematocrit during treatment. In 1214 non-cushingoid patients, transient leukopenia was reported once. Coombs-negative hemolytic anemia was reported in one patient. In » 300 patients with nonadrenal malignancy, 4% of cases showed some degree of anemia and two developed

pancytopenia. Thrombocytopenia and agranulocytosis have also occurred. Hepatic: Isolated abnormal liver function tests; suspected hepatotoxicity (less than

0.1%), cholestatic jaundice (hypersensitivity mechanism suspected). Miscellaneous: Vomiting, myalgia (3%). Fever, possibly related to therapy, occurred

in several patients on aminoglutethimide for < 4 weeks when given with other drugs.Over dosage: Symptoms: Over dosage has caused ataxia, somnolence, lethargy, dizziness, fatigue,

coma, hyperventilation, respiratory depression, nausea and vomiting, loss of sodium and water, hyponatremia, hypochloremia, hyperkalemia, hypoglycemia, hypovolemic shock due to dehydration and hypotension. Extreme weakness has been reported with divided doses of 3 g/day. No reports of death following doses estimated as large as 7 g.

The signs and symptoms of acute over dosage with aminoglutethimide may be aggravated or modified if alcohol, hypnotics, tranquilizers or tricyclic antidepressants have been taken at the same time.

Treatment: Gastric lavage and supportive treatment have been employed. Full consciousness following deep coma was regained <= 40 hours after ingestion of 3 or 4 g without lavage. No evidence of hematological, renal or hepatic effects were subsequently found. Consider dialysis in severe intoxication. Treatment includes usual supportive measures.

Patient Information:

May produce drowsiness or dizziness; patients should observe caution while driving or performing other tasks requiring alertness, coordination or physical dexterity.

May cause rash, fainting, weakness or headache; notify physician if pronounced. Nausea and loss of appetite may occur during the first 2 weeks of therapy; notify

physician if these persist or become pronounced.

3. ketoconazoleKetoconazole, is a potent and rather nonselective inhibitor of adrenal and gonadal steroid synthesis. This compound inhibits the cholesterol side chain cleavage, P450c17,C17,20-lyase, 3ß-hydroxysteroid dehydrogenase, and P450c11 enzymes required for glucocrticoid synthesis. The sensitivity of the P450 enzymes to this compound in mammalian tissues is much lower than that of the fungal enzymes, so that the inhibitory effects are seen only in high doses. This inhibition is compensated for by increased ACTH production and leads to increases in 17-deoxy steroids such as progesterone and aldosterone and to suppression of plasma rennin activity. Ketoconazole also has other endocrine effects. It displaces estradiol and dihydrotestosterone from sex hormone-binding protein in vitro and increases estradiol-testosterone ratioin plasma in vivo by different mechanism. The latter may be responsible for the gynecomastia sometimes seen with ketoconazole therapy.Ketoconazole has been used for the treatment of patients with Cushing’s disease due to several causes. Dosages of 200-1200 mg/d have produced a reduction in hormone levels and impressive clinical improvement in some patients in these preliminary studies.

4. Mifepristone (RU 486)

Mifepristone is a synthetic partial agonist steroid binds to glucocorticoid as well as to progesterone receptors and has been used experimentally in the treatment of Cushing’s syndrome.

5. Mitotane

Mitotane produces adrenal atrophy in dogs and interferes with biosynthetic pathways in the human adrenal cortex. This drug was administered 6-12 mg daily. About one-third of patients with adrenal carcinoma showed a reduction tumor mass and steroid production was decreased in tow-thirds. In 80% of patients, the toxic effects were sufficiently severe to require dose reduction. These included diarrhea, nausea, vomiting, depression, somnolence, and skin problems. The drug has been withdrawn from the market in the USA.

6. Amphenone B

Amphenone B is a more inhibitor of synthesis than mitotane, blocking hydroxylation at the 11, 17, and 21 positions. It does not have a destructive effect on the tissue, and the block of steroid leads to increased production of ACTH and hyperplasia of the gland. Amphenone causes central nervous system depression and gastrointestinal tract and skin

disorders and impairs liver and thyroid function. It is considered too toxic for use in humans.

7. Trilostane

Trilostane is also a 3ß-17-hydroxysteroid-dehydrogenase inhibitor that interferes with the synthesis of adrenal and gonadal hormones and is comparable to aminoglutethimide. Its side effects are predominantly gastrointestinal rather than the rashes and drowsiness seen with aminoglutethimide; side effects occur in about 50% of patients with both agents. There is no cross-resistance or crossover of side effects between these compounds.

6.2 Mineralocorticoid antagonists

In addition to agents that interfere with aldosterone synthesis, there are steroids that compete with aldosterone for binding sites and decreases its effect peripherally. Progesterone is mildly active in this respect.Spironolactone is a 17α-aceylthiospironolactone. Little is know about its metabolism. The onset of activity is slow, and the effects last for 2-3 days after the drug is discontinued. Its used in the treatment of primary aldosteronism in dosages of 50-100 mg/d. This agent reverses many of the findings of aldosteronism. It has been useful in establishing the diagnosis in some patients and in ameliorating the signs and symptoms when surgical removal of an adenoma is delayed. When used diagnostically for the detection of aldosteronism in hypokalemic patients with hypertension, dosage of 400-500 mg/d for 4-8 days with an adequate intake of sodium and potassium will restore potassium levels to or toward normal. This agent is useful in preparing these patients for surgery. Dosages of 300-400 mg/d for 2 weeks are used for this purpose and may reduce the incidence of cardiac arrhythmias.Spironolactone is also used in the treatment of hirsutism in women. Dosages of 50-200 mg/d cause a reduction in the density, diameter, and rate of growth of facial hair in patients with idiopathic hirsutism or hirsutism secondary to androgen excess. The effect con usually be seen in 2 months and becomes maximal in about 6 months. It may b due to inhibition of androgen production and an action at the hair follicle.Adverse effects reported for the spironolactone include hyperkalemia, menstrual abnormalities, gynecomastia, sedation, headache, gastrointestinal disturbances, and skin rashes.Drospirenone, a progestin is a new oral contraceptive, also antagonizes the effects of aldosterone.

Section VII: Corticosteroids for topical use7.0 Topical corticosteroidsThe basic principles are to use ointments rather than creams, and to use the least potent formulations as sparingly as possible. The first choice is 1% hydrocortisone ointment. More potent preparations are to be avoided for children and should be restricted to refractory cases. When other steroids are used, the potency must be checked.The different potencies of topical steroids cause confusion among doctors and parents. Most parents think that topical steroids are dangerous and any prescription must be accompanied by an explanation of the different potencies. Skin atrophy is in fact the main hazard of topical steroids. It results from regular use of the more potent preparations, especially on the face, but topical hydrocortisone virtually never causes atrophy. In older children, it is common to see severe and heavily lichenified patches of eczema confined

to the front of the knees, the wrists and the ankles. Such lesions may not respond well to low- potency steroids and in these sites it makes no sense to withhold a moderately potent steroid because of the fear of skin atrophy.The larger the areas of skin affected, and the more inflamed the skin, the greater the risk of systemic absorption of a topical steroid. There is therefore a theoretical risk of iatrogenic Cushing’s syndrome with widespread application of topical steroid. While eczema is not a fatal condition, the resulting handicap and damage can be severe. To withhold mild or moderately potent steroids in such patients for fear of adverse effects is unreasonable. Growth impairment occurs in up to 10% of children with atopic eczema but there is no evidence that use of low or moderate-potency topical steroid contributes to this. Nevertheless, long-term use of potent or very potent drugs over large areas of skin may inhibit growth.

7.1 Properties of topical steroidTopical corticosteroids have an anti-inflammatory activity on the skin as a result of four main actions: vasoconstriction, antipruritic, antimitotic, and immunosuppression. Topical corticosteroids into four potency groups according to their vasoconstrictive activity: mildly potent, moderately potent, potent very potent. The potency groupings give some indication of therapeutic efficacy and the likelihood of side effects. The potency of topical steroids can also be affected by the base used in the formulation producing changes in skin penetration. Effective treatment with topical steroids depends on the selection of the correct potency and formulation to meet the needs of the individual patient.Skin penetration is required for the anti-inflammatory activity of the topical steroids, but excessive penetration of potent steroids can lead to local and systemic side effects. Less potent steroids should be used in areas of thin skin such as the face,and in the children and the elderly.Topical steroids are generally well tolerated. Prolonged use, particularly of potent steroids, increases the risk of skin atrophy or suppression of the HPA axis. Treatment failure may result from under use and side effects may result from excessive use or use at inappropriate sites. Patients therefore need clear guidance on the quantities of steroid to apply and the frequency of treatment.

7.2 Guidance for the use of topical corticosteroids

1-Always start with low-potency preparations such as 1% hydrocortisone 2-Avoid using fluorinated steroids in infants

3-Avoid using high-potency steroids on face, neck and intertriginous areas

4-Always warn patients and parents of the side effects of steroid medications

5-Do not authorize repeat prescriptions for steroid preparations without proper follow-up

6-For eyelids and perioral areas, use ophthalmic steroid preparations

7-When using long-term topical steroid therapy with high-potency steroids, discuss the possibility of systemic absorption, HPA suppression and possible growth retardation

8-When inflammatory condition do not respond, or worsen, with treatment, suspect allergic contact dermatitis to one or more ingredients in the preparation used.

9-Avoid occlusive therapy involving plastic wrapping as side effects tend to be hastened and complication are more common.

10-Avoid abrupt discontinuation of topical steroid therapy. It is better to switch to lower-potency steroid medication and then gradually taper off.

11-The basic principles for topical corticosteroids are to use ointments rather than creams and to use the least potent drugs as sparingly as possible.

Section VIII: Corticosteroids for ophthalmic use8.0Corticosteroids for ophthalmic uses:Indications:Inflammatory conditions: For the treatment of steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, lid, sclera and anterior segment of the globe, such as: Allergic conjunctivitis; acne rosacea; superficial punctate keratitis; herpes zoster keratitis; iritis; cyclitis; selected infective conjunctivitis; vernal conjunctivitis; episcleritis; epinephrine sensitivity; and anterior uveitis.Ocular surgery: For treatment of postoperative inflammation following ocular surgery.Corneal injury: For corneal injury from chemical, radiation or thermal burns or penetration of foreign bodies.(See individual monographs for specific indications and administration and dosage.)

Administration and Dosage:Treatment duration varies with type of lesion and may extend from a few days to several weeks, depending on therapeutic response. If signs and symptoms fail to improve after 2 days, the patients should be re-evaluated. Relapse may occur if therapy is reduced too rapidly; taper over several days. Relapses, more common in chronic active lesions than in self-limited conditions, usually respond to retreatment.Actions:Pharmacology – Topical opthalmic corticosteroids exert an anti-inflammatory action. Aspects of the inflammatory process such as edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, deposition of collagen, scar formation and fibroblastic proliferation are suppressed. Steroids inhibit inflammatory response to inciting agents of mechanical, chemical or immunological nature. Topical ophthalmic corticosteroids are effective in acute inflammatory conditions of the conjunctiva, sclera, cornea, lids, iris and anterior segment of the globe; and in ocular allergic conditions. In ocular disease, route of administration depends on site and extent of disorder.The mechanism of the anti-inflammatory action is thought to be potentiation of epinephrine vasoconstriction, stabilization of lysosomal membranes, retardation of macrophage movement, prevention of kinin release, inhibition of lymphocyte and neutrophil function, inhibition of prostaglandin synthesis and, in prolonged use, decrease of antibody production.Inhibiting fibroblastic proliferation may prevent symblepharon formation in chemical and thermal burns. Decreased scarring with clearer corneas after topical corticosteroids is a result of inhibiting fibroblastic proliferation and vascularization.Contraindications: Acute epithelial herpes simplex keratitis (dendritic keratitis). Fungal diseases of ocular structures. Vaccinia. Varicella and most other viral diseases of the cornea and conjunctiva. Ocular tuberculosis. Hypersensitivity. After uncomplicated removal of a superficial corneal foreign body. Mycobacterial eye infection. Acute, purulent, untreated eye infections that may be masked or enhanced by the

presence of steroids (see Warnings).

Medrysone: Medrysone is not for use in iritis and uveitis; its efficacy has not been demonstrated.Warnings:Moderate-to-severe inflammation: Use higher strengths for moderate-to-severe inflammations. In difficult cases of anterior segment eye disease, systemic therapy may be required. When deeper ocular structures are involved, use systemic therapy.Ocular damage: Prolonged use may result in glaucoma, elevated IOP, optic nerve damage, defects in visual acuity and fields of vision, posterior subcapsular cataract formation or secondary ocular infections from pathogens liberated from ocular tissues. Check IOP and lens frequently if used for >= 10 days. In diseases that cause thinning of cornea or sclera, perforation has occurred with topical steroids.

Cataract surgery: The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.Mustard gas keratitis or Sjögren's keratoconjunctivitis: Topical steroids are not effective.Infections: Prolonged use may result in secondary ocular infections caused by suppression of host response. Acute, purulent, untreated eye infections may be masked or the activity enhanced by steroids. Fungal infections of the cornea have been reported with long-term local steroid applications. Therefore, suspect fungal invasion in any persistent corneal ulceration where a steroid has been used or is being used. Take fungal cultures when appropriate.Stromal herpes simplex keratitis treatment with steroid medication requires great caution; frequent slit-lamp microscopy is mandatory.Pregnancy: Category C. There are no adequate and well-controlled studies in pregnant women. Use only when clearly needed and when potential benefits outweigh potential hazards.Lactation: Topically applied steroids are absorbed systemically. It is not known if sufficient systemic absorption occurs to produce detectable quantities in breast milk. Therefore, because of the potential for serious adverse reactions in nursing infants, decide whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.Children: Safety and efficacy have not been established. Fluorometholone: Safety and efficacy in children < 2 years of age have not been established.Adverse Reactions: Glaucoma (elevated IOP) with optic nerve damage. Loss of visual acuity and field defects. Posterior subcapsular cataract formation. Delayed wound healing. Secondary ocular infection from pathogens, including herpes simplex and fungi

liberated from ocular tissues. Acute uveitis. Perforation of globe where there is corneal or scleral thinning. Exacerbation of viral, bacterial and fungal corneal infections. Transient stinging or burning. Chemosis. Dry eyes. Epiphora. Photophobia. Keratitis. Conjunctivitis. Corneal ulcers. Mydriasis. Ptosis. Blurred vision. Discharge. Discomfort.

Ocular pain. Foreign body sensation. Hyperemia. Pruritus (rimexolone). Rarely, filtering blebs have been reported with steroid use after cataract surgery. Systemic: Systemic side effects may occur with extensive use (eg, hypercorticoidism) Patient Information:Medical supervision during therapy is recommended.Instruct patients that use of contaminated ocular solutions can cause ocular infections and serious damage to the eye with subsequent loss of vision. To avoid contamination, do not touch applicator tip to any surface. Replace cap after using.If improvement in the condition being treated does not occur within 2 days, or if pain, redness, itching or swelling of the eye occurs, discontinue medication and notify the physician. Take care not to discontinue prematurely.Advise patients to immediately seek physician's advice concerning continued use of the present multidose container if they develop an intercurrent ocular condition (eg, trauma, ocular surgery, infection).Benzalkonium chloride is absorbed by contact lenses. Do not administer medications containing benzalkonium chloride while wearing soft contact lenses. Instruct patients to wait >= 15 minutes after instilling medication before inserting their lenses.

8.1 Classes of corticosteroids used in eye disorders

1. FLUOROMETHOLONE1- With 0.004% benzalkonium chloride, EDTA, polysorbate 80 and 1.4% polyvinyl alcohol.2- With 0.004% benzlkonium chloride, EDTA, polysorbate 80 and polyvinyl alcohol.3- With 0.01% benzalkonium chloride, EDTA, hydroxyethylcellulose and tyloxapol.4- With 0.005% benzalkonium chloride, EDTA, polysorbate 80 and 1.4% polyvinyl alcohol.5- With 0.0008% phenylmercuric acetate, white petrolatum, mineral oil and lanolin alcohol.

Indications:Inflammatory conditions: For steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe.Administration and Dosage:Consult a physician if there is no improvement after 2 days. Do not discontinue therapy prematurely. In chronic conditions, withdraw treatment by gradually decreasing the frequency of applications.Suspension: Shake well before using. Instill 1 to 2 drops into the conjunctival sac(s) 2 to 4 times daily. During the initial 24 to 48 hours, the dosage may be increased to 2 drops every 2 hours.

Ointment: Apply a small amount (» 1/2 inch ribbon) of ointment to the conjunctival sac 1 to 3 times daily. During the first 24 to 48 hours, the dosing frequency may be increased to one application every 4 hours.

2. MEDRYSONE 1- With 0.004% benzalkonium chloride, EDTA, 1.4% polyvinyl alcohol and hydroxypropyl methyl-cellulose.Indications:Inflammatory conditions: For the treatment of allergic conjunctivitis, vernal conjunctivitis, episcleritis and ephinephrine sensitivity.Administration and Dosage:Shake well before using. Instill 1 drop into the conjunctival sac up to every 4 hours.

3. PREDNISOLONE1- With benzalkonium chloride, EDTA, polysorbate 80, hydroxypropyl methylcellulose and sodium bisulfite.2- With 0.01% benzalkonium chloride, EDTA, polysorbate 80, hydroxypropyl methylcellulose and glycerin.3- With 0.01% benzalkonium chloride and EDTA.Indications:Inflammatory conditions: For the treatment of steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe, such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitis when the inherent hazard of steroid use is accepted to obtain an advisable diminution in edema and inflammation.Mild-to-moderate: For the treatment of mild-to-moderate noninfectious allergic and inflammatory disorders of the lid, conjunctiva, cornea and sclera (including chemical and thermal burns).Moderate-to-severe: Use higher strengths for moderate-to-severe inflammations. In difficult cases of anterior segment eye disease, systemic therapy may be required. When deeper ocular structures are involved, use systemic therapy.Corneal injury: Corneal injury from chemical, radiation or thermal burns or penetration of foreign bodies.Administration and Dosage:Solutions: Depending on the severity of inflammation, instill 1 or 2 drops of solution into the conjunctival sac up to every hour during the day and every 2 hours during the night as necessary as initial therapy. When a favorable response is observed, reduce dosage to 1 drop every 4 hours. Further reduction in dosage to 1 drop 3 to 4 times daily may suffice to control symptoms.Suspensions: Shake well before using. Instill 1 to 2 drops into the conjunctival sac 2 to 4 times daily. During the initial 24 to 48 hours, the dosing frequency may be increased if necessary. In cases of bacterial infections, concomitant use of anti-infective agents is mandatory.If signs and symptoms do not improve after 2 days, re-evaluate the patient.

Dosing may be reduced, but advice patients not to discontinue therapy prematurely. In chronic conditions, withdraw treatment by gradually decreasing the frequency of applications.

4. DEXAMETHASONE1- With polysorbate 80, EDTA, 0.1% sodium bisulfite, 0.25% phenylethanol, 0.02% benzalkonium chloride.2- With 0.01% benzalkonium chloride, EDTA, 0.5% hydroxypropylmethylcellulose, polysorbate 80.3- With lanolin anhydrous, parabens, PEG-400, white petrolatum and mineral oil.4- With white petrolatum and mineral oil.Indications:Inflammatory conditions: Treatment of steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe, such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, selected infective conjunctivitis when the inherent hazard of steroid use is accepted to obtain advisable edema and inflammation diminution.Corneal injury: Corneal injury from chemical, radiation or thermal burns or penetration of foreign bodies.Administration and Dosage:Solutions: Instill 1 to 2 drops into the conjunctival sac every hour during the day and every 2 hours during the night as initial therapy. When a favorable response is observed, reduce dosage to 1 drop every 4 hours. Further reduction in dosage to 1 drop 3 or 4 times daily may suffice to control symptoms.Suspension: Shake well before using. Instill 1 or 2 drops in the conjunctival sac(s). In severe disease, drops may be used hourly, being tapered to discontinuation as inflammation subsides. In mild disease, drops may be used <= 4 to 6 times daily.Ointment: Apply a thin coating of ointment 3 to 4 times a day. When a favorable response is observed, reduce the number of daily applications to twice daily and later to once daily as a maintenance dose if this is sufficient to control symptoms.The ointment is particularly convenient when an eye pad is used. It may also be the preparation of choice for patients in whom therapeutic benefit depends on prolonged contact of the active ingredients with ocular tissues.

5. RIMEXOLONE1- With 0.01% benzalkonium chloride, polysorbate 80 and EDTA.Complete prescribing information begins in the Ophthalmic Corticosteroids group monograph. (Reference) Indications:Inflammatory conditons: Treatment of anterior uveitis.Ocular surgery: Treatment of postoperative inflammation after ocular surgery.Administration and Dosage:Shake well before using.

Postoperative inflammation: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily begining 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period.Anterior uveitis: Apply 1 to 2 drops into the conjunctival sac of the affected eye every hour during waking hours for the first week, 1 drop every 2 hours during waking hours of the second week, and then taper until uveitis is resolved.

6. LOTEPREDNOL ETABONATE1- With 0.01% benzalkonium chloride and EDTA.Complete prescribing information begins in the Ophthalmic Corticosteroids group monograph. (Reference) Indications:0.2% suspension: Inflammatory conditions: For the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis.0.5% suspension: Inflammatory conditions: For the treatment of steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective conjunctivitis, when the inherent hazard of steroid use is accepted to obtain an advisable dimunition in edema and inflammation.Ocular surgery: Treatment of postoperative inflammation following ocular surgery.Administration and Dosage:Approved by the FDA: March 9, 1998.Shake well before using.0.2% suspension: Instill 1 drop into the affected eye(s) 4 times daily.0.5% suspension: Steroid responsive disease: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily. During the initial treatment within the first week, the dosing may be increased up to 1 drop every hour. Advise patients not to discontinue therapy prematurely. If signs and symptoms fail to improve after 2 days, re-evaluate the patient.Postoperative inflammation: Apply 1 to 2 drops into the conjunctival sac of the operated eye(s) 4 times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period.

Section IX: Corticosteroids chemical and proprietary names9.0 Drugs names and properties:1. Alclometasone Dipropionate It’s a corticosteroid of general properties. Store in airtight container. Used topically in the treatment of various skin disorders. It is usually employed as a cream or ointment containing 0.05%.

Proprietary namesAclosone, Aclovate, Delonal, Legederm, Logoderm, Modrason, Modrasone.

2. Aldosterone Aldosterone is the main mineralocorticoid secreted by the adrenal cortex. It has no anti-inflammatory properties. It has been used in association with a glucocorticoid in the treatment of adrenocortical

insufficiency. Doses of 500 μg have been given by slow intravenous injection or by intramuscular

injection. It has also been used as the sodium succinate.

Proprietary namesAldocorten.

3. Amcinonide It’s a corticosteroid of general properties. Amcinonide is a corticosteroid used topically in the treatment of various skin

disorders. It is usually employed as a cream, lotion, or ointment containing 0.1%.

Proprietary namesAmciderm, Amcinil, Amicla, Cyclocort, Penticort.

4. Beclomethasone dipropionate. It’s a corticosteroid of general properties Adrenal suppression may occur in some patients treated with high-dose long-term

inhalation therapy for asthma.Adrenal suppression: some cases have occurred with patients receiving doses below 1.5 mg daily. Candidiasis: its uncommon finding in children compared to adults using beclomethasone inhalation for asthma. But the incidence increase in children receiving steroids than in those who do not. Effects on the bones: studies have shown that beclomethasone dipropionate can suppress bone metabolism.Effects on the lungs: the developments of pulmonary eosinophilia have been reported in-patient treated with inhaled beclomethasone.Hypersensitivity. Beclomethasone dipropionate is used for asthma, skin disorders, and ulcerative colitis Asthma: compound used to exert topical effect on the lungs without producing any systemic action (in order to avoid systemic side effect). An inhalation aerosol is used to administer the drug. Dosage size varies from patient to another; according to the severity, age…etc. Children aged 2 years or under are not allow to use steroids therapy unless if they are not responding to other drugs or if the asthma attack is very severe.

Skin disorders: different dosage forms (e.g. cream, lotion, and ointment), and different concentrations are used for skin disorders. Ulcerative colitis: beclomethasone dipropionate 5 mg enemas were found to be very effective in the treatment of acute attacks of ulcerative colitis.

Proprietary namesAerobec, Aldécine, Aldecin, Béconase, Bécotide, Beclo Asma, Beclo Rino, Beclodisk, Becloforte, Beclorhinol, Beclosona, Becloturmant, Beclovent, Becodisk, Becodisks, Beconase, Beconase AQ, Beconase Aquosum, Beconase Dosier-Spray, Beconasol, Becotide, Bronco-Turbinal, Cleniderm, Clenil, Clenil-A, Dereme, Dermisone Beclo, Inalone, Menaderm Simple, Menaderm Simplex, Propaderm, Rino-Clenil, Rino Clenil, Sanasthmax, Sanasthmyl, Turbinal, Vancenase, Vancenase AQ, Vanceril, Viarin, Viarox.Aerosoma, Beclonarin, Batasol, Clenil Compositum, Clenil Compositum-A, Menaderm, Menaderm Clio, Menaderm Otologico, Propaderm-A, Propaderm-C, Recto Menaderm, Venoflavan, Ventide, Ventolin Flogo, Ventolin Plus.

5. Betamethasone It is a glucocorticoid given orally, parentrally, by local injection, by inhalation, or

applied topically in the management of various disorders in which corticosteroids are indicated.

Its lack of mineralocorticoid properties makes betamethasone particularly suitable for treating cerebral edema and congenital adrenal hyperplasia.

It’s a corticosteroid of general properties. Subtypes of betamethasone:a- Betamethasone acetateb- Betamethasone benzoatec- Betamethasone dipropionated- Betamethasone sodium phosphatee- Betamethasone valerate

Proprietary namesAlphatrex, Beben, Bedermin, Bentelan, Betacort, Betaderm, Betagel, Betamatil, Betapred, Betatrex, Betnelan, Betnelan-V, Betnasol, Betnasol-V, Betnasol-WL, Betneval, Betnovat, Betnovate, Betnovate RD, Betoid, Bextasol, B-S-P, Célestène, Célestoderm, Celestan, Celestan—V, Celestoderm, Celestoderm-V, Celeston, Celeston valerate, Celestone, Celestone M, Celestone Phosphate, Celestone V, Cordes Beta, Diproderm, Diprolène, Diprolene, Diprolene Glycol, Diprosis, Diprosone, durabetason, Ecoval, Ectosone, Euvaderm, Maxivate, Minisone, Novobetamet, Paucisone, Persivate, Prevex B, Sclane, Topilene, Topisone, Valisone, Vista-Methasone,Alergical, Alfaflor, Anauran, Antibioticoedermin B, Beben Clorossina, Bentelan, Beta Micutrin, Betabioptal, Betamatil con Neomicina, Betamida, Betnelan-VC, Betnelan-VN, Betnesalic, Betnesol, Betnesol-N, Betnesol-VN, Betneval-Néomycine, Betnovat mad chinoform, Betnovate Rectal ointment, Betnovate-N, Biorinil, Bronsal, Brumeton Colloidale S, Célestamine, Célestène Chronodose, Célestoderm Néomycine, Celesemine, Celestamine, Celestan Depot, Celestoderm Gentamic,

Celestoderm met Garamycin, Celestoderm met Neomycine, Celestoderm-V with Garamycin, Celestoform, Celeston bifas, Celeston valerat comp., Celeston valerat med chinoform, Celeston valerat med gentamicin, Celestone Soluspan, Celestone-VG, Cuatroderm, Deltavagin, Diproform, Diprogen, Diprogenta, Diprophos, Diprorecto, Diprosalic, Diprosept, Diprosone Depot, Diprosone Duopack, Diprosone Néomycine, Diprostène, durabetagent, Eucoval con Neomicina, Eubetal, Eubetal Anibiotico, Euvaderm, Fenistil Plus, Flourorinil, Fucibet, Fucicort, Garasone, Gentalyn Beta, Glido, Glido Néomycine, Lotricomb, Lotriderm, Lotrisone, Micomplex, Micutrin Beta, Nasotic Oto, Ophtasone, Otocusi Enzimatico, Quadriderm, Quadriderme, Ramatocina, Raquivit, Resorborina, Rinofluimucil, Rinojet, Rinojet Sf senza Fenilefrina, Scalmine, Sclane, Stanoval, Sulmycin mit Celestan-V, Triderm, Valisone-G, Vipsgal, Vista-Methasone N, Visbulefarite, Visumetazone Antibiotico, Visumidriatic Antiflogistico. 6. Budesonide It’s a corticosteroid of general properties. Budesonide is a glucocorticoid used by inhalation for asthma (administered by

metered aerosol, dry powder inhaler, and pressurized inhaler). Budesonide can be used for children (including those under 1 year old) for the

treatment of asthma or to control wheezing. Budesonide is also used topically for the treatment of various skin disorders. It’s employed as a cream or ointment containing 0.025%.

Proprietary namesBidien, Preferid, Pulmicort, Rhinocort, Topinasal.

7. Ciclomethasone Ciclomethasone is a glucocorticoid, which has been applied topically in allergic and

inflammatory skin disorders. It has also been given by inhalation in asthmatic conditions.

Proprietary namesCycloderm, Telocort.

8. Clobetasol Propionate It’s a corticosteroid of general properties. Clobetasol propionate is used topically in the treatment of various skin disorders. It is usually employed as a cream, ointment, or scalp preparation containing 0.05%.

Proprietary namesClobesol, Clovate, Declban, Dermoval, Dermovat, Dermovate, Dermoxin, Dermoxinale, Termovate, Dermovate-NN.

9. Clobetasone Butyrate It’s a corticosteroid of general properties.

Clobetasone butyrate is used as an eye drops for the treatment of intra-ocular pressure.

It has been reported that clobetasone butyrate eye drops have less side effects on the eyes than other eye drops containing corticosteroids such as hydrocortisone, betamethasone, prednisolone, or dexamethasone.

It is also applied topically for the treatment of various skin disorders. It is usually employed as a cream or ointment containing 0.05%, and is also used as

eye drops containing 0.1%.

Proprietary namesCloptison, Emovat, Emovate, Eumovate, Visucloben, Cloptison-N, Eumovate-N, Trimovate.

10. Clocortolone Pivalate It’s a corticosteroid of general properties. It is used topically in the treatment of various skin disorders Clocortolone hexanoate has been used similarly.

Proprietary namesLenen, Cort-Tavegil, Crino-Kaban N, Kaban, Kabanimat, Procto-Kaban.

11.Cloprednol It’s a corticosteroid of general properties. It has been given by mouth in various disorders.

Proprietary nameCloradryn, Novacort, Syntestan.

12.Cortisone Acetate It’s a corticosteroid of general properties. Cortisone acetate is readily absorbed from the gastro-intestinal tract, and the cortisone

is rapidly converted in the liver to its active metabolite, hydrocortisone (cortisol). The biological half-life of cortisone itself is only about 30 minutes. Absorption of cortisone from intramuscular sites is slower than absorption it orally. Cortisone is a glucocorticoid secreted by the adrenal cortex. Cortisone acetate has some mineralocorticoid properties and has been used mainly for

the replacement in Addison’s disease or chronic adrenocortical insufficiency secondary to hypothyroidism.

Cortisone acetate has been used in the treatment of many allergic and inflammatory disorders, but other corticosteroids are preferred since cortisone has sodium-retaining properties.

Proprietary namesAdreson, Altesona, Cortal, Cortate, Cortelan, Cortstab, Cortisyl, Cortogen, Cortone, Cortone Acetate, Cortone Acetato, Antiblefarica, Belfarida, Cortisona Neomi, Dutimelan, Gingilone.

13.Cortivazol It’s a glucocorticoid with general properties. It has been given orally, and by intra-articular injection.

Proprietary namesAltim, Diaster.

14.Deflazacort It’s a glucocorticoid with general properties. It is said to have fewer systemic side effects than other corticosteroids such as

prednisone or methylprednisolone. It has been given orally.

Proprietary namesCalcort, Deflan, Fentadin.

15.Deoxycortone Acetate Deoxycortone pivalate is a derivative of deoxycortone acetate. It’s a corticosteroid of general properties. Overdoses of deoxycortone acetate may produce excessive sodium and water

retention leading to hypertension, edema, pulmonary congestion, and signs and symptoms of congestive heart failure.

Salt restriction is advisable in such cases. Excessive loss of potassium may result in muscular weakness and paralysis. Deoxycortone is a mineralocorticoid secreted by the adrenal cortex and has its general

properties. It has been used in the treatment of Addison’s disease and other adrenocortical

deficiency states. Deoxycortone acetate has benn administered as a subcutaneous implant, and as oily

intramuscular injection.

Proprietary names Cortiron, Syncortyl.

16.Desonide It’s a corticosteroid of general properties. It’s used topically in the treatment of various skin disorders. It is usually employed as a cream or ointment or ear drops containing 0.05%. The pivalate ester has also been used in dermatological preparations and the sodium

phosphate in ophthalmological preparations.

Proprietary namesApolar, Cirkan a la Prednacinolone, Desonicx, Desowen, Locapred, Reticus, Reticus Antimicotico, Sine Flour, Sterax, Topifug, Tridésonit, Tridesilon.

17.Desoxymethasone It’s a corticosteroid of general properties. Desoxymethasone is a corticosteroid used topically in the treatment of various skin

disorders. It is usually employed as a cream, gel, lotion, or ointment; concentrations used range

is from 0.05% to 0.25%.

Proprietary names Flubason, Ibril, Ibril med salicylsyra, Stiedex, Stiedex LP, Stiedex LPN, Topicort, Topicort Composto, Topicorte, Topiderm, Topifram, Topisalen, Topisolon.

18. Dexamethasone Dexamethasone is a glucocorticoid given orally, parenterally, by local injection, by

inhalation, and applied topically in the management of various disorders in which corticosteroids are indicated.

Subtypes of dexamethasone:a. Dexamethasone Acetate (1.1 mg is equivalent to 1 mg of

dexamethasone).b. Dexamethasone Isonicotinate (1.3 mg is equivalent to 1 mg of

dexamethasone).c. Dexamethasone Phosphate.d. Dexamethasone Sodium Metasulphobenzoate (1.5 mg is

equivalent to 1 mg of dexamethasone).e. Dexamethasone Sodium Phosphate (1.1 mg is equivalent to 1 mg

of dexamethasone). It’s a corticosteroid of general properties. Serum concentrations of dexamethasone are reported to be decreased by phenytoin,

and vice versa. Dexamethasone is readily absorbed from the gastro-intestinal tract. Its biological half-life in the plasma is about 190 minutes Binding of dexamethasone to plasma is less than for most other corticosteroids. Dexamethasone has been used in the form of free alcohol or in one of the esterified

forms in the treatment of all conditions in which corticosteroid therapy is indicated. Its lack of mineralocorticoid properties makes dexamethasone suitable for treating

cerebral edema and suppressing corticotrophin secretion in congenital adrenal hyperplasia.

Dexamethasone is also used orally in the dexamethasone suppression tests for the diagnosis of Crushing’s syndrome.

Dexamethasone is administered parentrally for intensive therapy or in emergencies. For ophthalmic disorders or for topical applications in the treatment of various skin

disorders, dexamethasone or sodium phosphate ester is usually employed; concentrations are usually expressed in terms of dexamethasone or dexamethasone phosphate and are commonly 0.05 to 1% for eye drops or ointments, and 0.1% for topical skin preparations.

Dexamethasone is also used by inhalation in the management of asthma.

Dexamethasone has been administered intravenously and orally for the prevention of nausea and vomiting induced by cancer chemotherapy.

Dexamethasone is said to be effective in the treatment of alcohol withdrawal syndrome, hirsutism, malaria, meningitis, and mountain sickness.

Proprietary namesAeroseb-Dex, afpred-1, Ak-Dex, Anemul Mono, Artosone, Auxiloson, Auxisone, Baldex, Cébédex, Cortidexason, Cortisumman, Dalalone D.P., Décadron, Decaderm in Estergel, Decadran, Decadron, Decadron Depot, Decadron Phosphat, Decadron Phosphate, Decadron-LA, Decaspray, Decoflour, Dectancyl, Deronil, Desalark, Deseronil, Dexa in der Ophtiole, Dexabene, Dexa-Brachialin N, Dexa-Clinit, Dexacortal, Dexa-Effecton, Dexa-Inject, Dexalocal, Dexamed, Dexamiso, Dexamonozon, Dexamonozon N, Dexane, Dexaplast, Dexapos, Dexa-ratiopharm, Dexa-sine SE, Dexasone, Dexasone 10, Dexasone 4, Dexasone LA, Dexamethasone, Etacortilen, Firmalone, Fortecortin, Fosfodex, Hexadrol, Hexadrol Phosphate, Isopto Maxidex, Lokalison-F, Lokalison-universale, Luxazone, Maxidex, Megacort, Mephamésone, Millicortène, Oradexon, Predni-F-Tablinen, Sokaral, Soldesam, Solone, Soludécadron, Spresadex, Spondy-Dexa, Totocortin, Tuttozem N, Visumetazone.

2. Dichlorisone Acetate It’s a corticosteroid of general properties. It is used topically in the treatment of various skin disorders. It is usually employed as a cream or ointment containing 0.25% or 1%.

Proprietary namesAstroderm, Dermaren, Diclasone, Diclasone Gentamicina, Dicloderm Forte.

3. Diflorasone Diacetate It’s a corticosteroid of general properties. It is used topically in the treatment of various skin disorders. It is usually employed as a cream or ointment containing 0.05%.

Proprietary namesBexilona, Dermaflor, Dermonilo, Florone, Flutone, Fulixan, Maxiflor, Murode, Psorcon, Soriflor, Sterodelta.

4. Diflucortolone Valerate It’s a corticosteroid of general properties. It is a corticosteroid used topically in the treatment of various skin disorders. It is usually employed as a cream or ointment containing 0.1% or 0.3%.

Proprietary names Binerisona, Claral, Corti-floural, Dermaflogil, Dermobios, Dermobios Oto, Dermaval, Dicortal, Impetex, Flu-Cortanest, Nérisone C, Neriforte, Nerisona, Nerisona C, Nerisone, Temetex, Temetex C, Temetex Compositum, Travocort.

5. Difluprednate It’s a corticosteroid of general properties. It has been used topically in the treatment of various skin disorders It is usually employed as a cream, gel, or ointment; concentrations used range from

0.02% to 0.05%.

Proprietary namesÉpitopic, Epitopic Néomycine.

6. Domoprednate It’s a corticosteroid of general properties. It is under investigation for use topically in the treatment of various skin disorders.

(The drug is still under examinations; no brand has been produced yet).

7. Endrysone It’s a corticosteroid of general properties. It is used as eye drops and eye ointments, containing 0.5%.

Proprietary namesAldrisone, Aldrisone VC. 8. Fluazacort It’s a corticosteroid of general properties. It has been used topically in the treatment of various skin disorders. It is usually employed as a cream containing 0.025%.

Proprietary namesAzacortid.

9. Fluclorolone Acetonide It’s a corticosteroid of general properties. It is used topically in the treatment of various skin disorders. It is usually employed as a cream or ointmentcontaining 0.025%.

Proprietary namesCutanit, Topilar.

10.Fludrocortisone Acetate Fludrocortisone acetate is a corticosteroid with potent mineralocorticoid activity. It is given orally in the treatment of primary adrenal insufficiency, usually as an

adjunct to hydrocortisone replacement therapy. The main side effects are fluid retention, hypokalaemia, and hypertension. Fludrocortisone acetate has a glucocorticoid action about 10 times as potent as

hydrocortisone and mineralocorticoid effects more than 100 times as potent.

Their side effects are mainly due to the mineralocorticoid activity. Fludrocortisone is readily absorbed from the gastro-intestinal tract. Fludrocortisone is applied topically to the skin, eye, and ear in the treatment of

various disorders. It has been employed as cream, ointment, gel, or drops, usually in a concentration of

0.1%. The main indications of fludrocortisone are:

a. Adrenal insufficiencyb. Congenital adrenal hyperplasiac. Hyperkalaemiad. Hypoaldosteronisme. Orthostatic hypotensionf. And various skin disorders

Proprietary namesBléphaseptyl, Florinef, Florinef Acetaat, Florinef Acetate, Fludronef, Novicort, Panotile, Panotile N. 11.Flumethasone It’s a corticosteroid of general properties. Flumethasone pivalate is a glucocorticoid used topically in the treatment of

various skin disorders. It is usually employed as cream, ointment, or lotion containing 0.02%. Flumethasone pivalate is also used in eardrops in a concentration of 0.02% with

clioquinol 1%.

Proprietary namesLocacortène, Locacortène-Vioforme, Locacorten, Locacorten c. Neomycin, Locacorten Tar, Locacorten Vioform, Locacorten-Vioform, Localasen, Locasalène, Locasalen, Locorten, Locorten Neomicina, Locorten Tar, Locortene, Locortene Vioformo, Locorten-Vioformo, Locorten-Vioformio, Logamel, Losalen, Psocortène.

12.Flunisolide It’s a corticosteroid of general properties. Flunisolide is a glucocorticoid used as a nasal spray for the prophylaxis and treatment

of allergic rhinitis. Flunisolide is also used by inhalation from a metered aerosol in the management of

asthma.

Proprietary namesAeroBid, Bronalide, Bronilide, Gibiflu, Inhacort, Lokilan, Nasal, Lunibron-A, Lunis, Nasalide, Rhinalar, Syntaris, Syntaris Bronchiale.

13.Fluocinolone Acetonide It’s a corticosteroid of general properties. Fluocinolone acetonide is used topically in the treatment of various skin disorders.

It is usually employed as a cream, gel, lotion, or ointment; concentration used range from 0.0025% to 0.2%.

Fluocinolone acetonide has also been used topically in the treatment of inflammatory eye, ear, and nose disorders.

Proprietary names Alfabios, Alfa-Fluorone, Alvadermo Fuerte, Abrasone Rectal, Alergical, Anatopic, Anasilpiel, Antibio-Synalar, Artrodesmol Extra, Bazalin, Co Fluocin Fuerte, Coderma, Cortalar, Cortamide, Cortiespec, Cortiplastol, Cortoderm, Cortanest Plus, Cranolona, Dermaisom, Dermaplus, Dermobeta, Dermofil, Dermoersa, Dermolin, Doricum Semplice, Doricum, Elasven, Elasven Neomicina, Esacinone, Esilon, Fluo Fenicol, Fluo Vaso, Fluocid Forte, Fluocinil, Fluocit, Fluoderm, Fluodermo Fuerte, Fluodermol, Fluomix Same, Fluomicetina, Fluonid, Fluonide, Fluovitef, Gelidina, Intradermo Cort, Intradermo Corticosteroi, Intradermo Cort Ant Fung, Isnaderm, Jellin, Jellin polyvalent, Jellin-Neomicina, Lauromicina, Leniderm, Localyn, Localyn S.V., Localyn-Neomicina, Mecloderm F, Meclutin, Midacina, Myco Synalar, Myco-Jellin, Myco-Synalar, Nefluan, Neo Analsona, Neo-Synalar, Neoderm Ginecologico, Omniderm, Otomidrin, Oxidermiol Fuerte, Poxider, Procto-Jellin, Proctolyn, Procto-Synalar, Radiocin, Sterolone, Straderm, Synalar, Synalar + D.B.O., Synalar Bi-Otic, Synalar C, Synalar med chinoform, Synalar N, Synalar Néomycine, Synalar Neomicina, Synamol, Synemol, Synobel, Topiflour, Ultraderm, Vinciseptil Otico.

14.Fluocinonide It’s a corticosteroid of general properties. Fluocinonide is a corticosteroid used topically in the treatment of various skin

disorders. It is usually employed as a cream, gel, lotion, ointment, or scalp application

containing 0.05%.

Proprietary namesCombiderm, Cusigel, Flu 21, Garia, Klariderm, Lidecomb, Lidemol, Lidex, Lyderm, Metosyn, Novoter, Novoter Gentamicina, Proctonide, Topsym, Topsym polyvalent, Topsyn Neomicina, Topsyn Néomycine, Topsyne, Trisyn,Vasoderm E, Vipsogal.

15.Fluocortin Butyl Fluocortin butyl is a corticosteroid of general properties. It is used topically in the treatment of various skin disorders. It has been employed as a cream or ointment containing 0.75%. Fluocortin butyl has also been used in the form of a dry powder inhalation for the

management of allergic rhinitis.

Proprietary namesBi-Vaspit, Lenen, Vaspit.

16.Fluocortolone

It’s a corticosteroid of general properties. Fluocortolone and its esters are corticosteroids used topically in the treatment of

various skin disorders. They are usually employed as a cream or ointment; concentrations usually used are

0.1% of the hexanoate with 0.1% of the pivalate and 0.25% of the hexanoate with 0.25% of either the free alcohol or pivalate ester.

The pivalate and hexanoate esters have also been used together in ointments or suppositories for the treatment of anorectal disorders.

Proprietary namesDermocur, Doloproct, Eczecur, Mycocur, Myco-Ultralan, Protocort, Syracort, Ultracur, Ultradil, Ultradil Plain, Ultralan, Ultralan-crinale, Ultralan-D, Ultralan M, Ultralanum, Ultralanum Plain, Ultraproct. 17.Fluorometholone It’s a corticosteroid of general properties. Fluorometholone acetate 1.1 mg is equivalent to 1 mg of fluorometholone. It is used with topramycin in ophthalmic suspensions. Fluorometholone is a glucocorticoid employed, usually as eye-drops containing 0.1%

in the treatment of allergic and inflammatory conditions of the eye. Prolonged application to the eye has caused raised intra-ocular pressure and reduced

visual functions. Fluorometholone has also been used topically in the treatment of various skin

disorders.

Proprietary namesBexicortil, Cortisdin Urea, Delmeson, Efemolin, Efemoline, Efflumycin, Efflumidex, Flarex, Fluaton, Flucon, Flumetol, Fluometol Semplice, Flumetol Antibiotico, Fluorvas, FML, FML Forte, FML Liquifilm, FML-S Liquifilm, FML Neo, FML-Neo, Isopto Flucon, Loticort, Psoriasdin Corticoide, Regresin, Regresin Hemorroidal.

18.Fluprednidene Acetate It’s a corticosteroid of general properties. It is used topically in the treatment of various skin disorders. It is usually employed as a cream, lotion, or ointment containing 0.1%, and

sometimes 0.05% is also used.

Proprietary namesCandio-Hermal, Corticoderm, Corticoderm comp., Crinohermal FEM, Crinohermal fem neu, Decoderm, Decoderm comp., Decoderm compositum, Decoderm trivalent, Decoderm Trivalente, Sali-Decoderm, Vobaderm, Vobaderm Plus. 19.Fluprednisolone It’s a glucocorticoid of general properties.

It has been used orally in the form of free alcohol.

Proprietary namesSelectren.

20.Flurandrenolone It’s a corticosteroid of general properties. It is used topically in the treatment of various skin disorders. It is usually employed as a cream or ointment containing 0.0125%.

Proprietary namesCordran, Cordran-N, Cordran SP, Dernison, Dernison con Neomicina, Dernison Neomicina, Haelan, Haelan-C, Haelan-X, Sermaform, Sermaka, Sermaka N.

21.Fluticasone Propionate It’s a corticosteroid of general properties. Fluticasone propionate is poorly absorbed from the gastro-intestinal tract and

undergoes extensive first pass metabolism. Fluticasone propionate is administered by nasal spray in the prophylaxis treatment of

allergic rhinitis. It has been tried orally in the treatment of inflammatory bowel disease. Fluticasone propionate, administered orally, was reported to be useful in the treatment

of Crohn’s disease.

Proprietary namesFlixonase, Flutide Nasal, Flutinase.

22.Formocortal Formocortal is a corticosteroid of general properties. It has been used in the treatment of inflammatory eye disorders as eye drops and eye

ointments containing 0.05%. Prolonged application to the eye has caused raised intra-ocular pressure and reduced

visual functions.

Proprietary namesFormoftil, Formomicin.

23.Halcinonide Halcinonide is a corticosteroid of general properties. It’s used topically in the treatment of various skin disorders. It is usually employed as a cream, lotion, or ointments in concentrations ranges from

0.025% to 0.1%.

Proprietary namesHalciderm, Halcimat, Halog, Halog-E, Heyden Dermol.

24.Halobetasol Propionate Halobetasol Propionate is a corticosteroid of general properties. It’s used topically in the treatment of various skin disorders. It is usually employed as an ointment containing 0.05%.

Proprietary namesUltravate.

25.Halometasone Halometasone is a corticosteroid of general properties. It’s used topically in the treatment of various skin disorders. It is employed as a cream or ointment containing 0.05% of halometasone

monohydrate.

Proprietary namesSicorten, Sicorten plus.

26.Hydrocortamate Hydrochloride Hydrocortamate Hydrochloride is a corticosteroid of general properties. It is used topically in the treatment of various skin disorders.

Proprietary namesCortanest, Etamicina.

27.Hydrocortisone Hydrocortisone, the main glucocorticoid secreted by the adrenal cortex, is given as

the free alcohol or in esterified form. It is given orally, parentrally, by local injection, or applied topically in the

management of various disorders in which corticosteroids are indicated. Intravenous therapy with water-soluble esters is used in emergencies to give a rapid

response. Hydrocortisone is used with fludrocotisone for replacement therapy in adrenal

insufficiency. Hydrocortisone is a corticosteroid of general properties. Hydrocortisone is readily absorbed from the gastro-intestinal tract and peak blood

concentrations are attained in about an hour. Hydrocortisone is metabolized in the liver and most body tissues to hydrogenated and

degraded forms such as tetrahydrcortisone and tetrahydrocortisol. The metabolized hydrocortisone forms are excreted in the urine. Hydrocortisone is preferred over cortisone; since cortisone need to convert in the liver

to hydrocortisone. Sub-types of hydrocortisone:A- Hydrocortisone AcetateB- Hydrocortisone Butyrate

C- Hydrocortisone CypionateD- Hydrocortisone HemisuccinateE- Hydrocortisone Sodium PhosphateF- Hydrocortisone Sodium SuccinateG- Hydrocortisone Valerate Proprietary NamesActocortina, Adacor, Aeroseb-HC, A-Hydrocort Univial, Alfason,Algicortis, Alocort, Anflam, Anuprep HC, Barriere-HC, Buccalsone,Carmol HC, Colifoam, Colofoam, Cordes H, Corlan, Cortacream Bandgage,Cortaid, Cortamed, Corlan, Cortacet,Cortacream Bandage, Cortaid, Cortamed, Cortate, Cort-Dome, Cortef, Cortenema, Cortic, Ccorticream, Cortidro, Corttifair,Cortifoam, Cortiment, Cortoderm, Corril, Covocort, Crema Transcutan Astier, Cutaderm, Dermacalm, Dermacort, Derm-Aid, Dermocortal, dermolate,Dermosa Cusi Hidrocort, Dilucort, Dioderm, Efcortelan, efcortelan Soluble, Efcortesol, Egocort Cream, Ekzesin, Emocort, Ficortril,flebocortid, Glycocrtison H,Glocortisone H, Hc45, Hemril-HC, Hidroaltesona, Hycor, Hycort, Hyderm, Hydro-adreson, Hydrocortistab, Hydrocortisyl, Hidrocortone, Hidrocortone Acetate, Hidrocortone Phosphate, Hidrosone, Hysone, Hysone-A, Hytone, Idracemi, Idrocortigamma, Lanacort, Lenirit, Locoid, Locoidon, Massengill, Medicated, Mildison, Mildison Lipocream, Munitren H, Mylocort, Nordicort, Novohydrocort, Nutracort, Orabase HCA, Oralsone, Pandel, Paro, Penecort, Prevex HC, Procort, Proctocort, Procutan, Rapicort, Rectocort, Retef, sagittacortin, Sanatison Mono, Sarna HC, Schericur, Scheroson F, Sigmacort, Siguent Hycor, Sintorat, Skincalm, Solu-Cortef, Solu-Glyc, Squibb-HC, Supralef, Synacort, Texacort, Timocort, Unicort, Uniderm, Urecortyn, Velopural, Waspeze Hydrocortisone, Westcort, Zenoxone.

28.Medrysone Medrysone is a corticosteroid of general properties. It is a glucocorticoid employed usually as eye drops containing 1%, in the topical

treatment of allergic and inflammatory conditions of the eye.

Proprietary namesHMS Liquifilm, Medriusar, Ophtocortin, spectramedryn.

29.Meprednisone It’s a glucocorticoid with general properties. It has been given by mouth and injection.

30.Methylprednisolone Methylprednisolone is a corticosteroid of general properties. Methylprednisolone is indicated orally, parenterally, by local injection, or applied

topically in the management of various disorders in which corticostroids are indicated.

The half-life of methylprednisolone is slightly longer than prednisolone.

Methylprednisolone is absorbed from joints over a week but is more slowly absorbed following deep intramuscular injection.

Methylprednisolone is administered for blood disorders, organ and tissue transplantation, bone disorders, eye disorders, lupus erythematoses, cerebral edema, rheumatoid disease, septic shock, skin disorders, spinal cord injury, and for vertigo.

Proprietary namesA-Methapred Univial, Asmacortne, Caberdelta M, Dépo-Médrol, Depo Moderin, Depo-Medrate, Depo-Medrol, Depomedrone, Depo-Predate, Esametone, Firmacort, Médrol, Medrate, Medrol, Medrol Topical, Medrol Veriderm, Medrone, Mega-Star, Metilbetasone Solubile, Metypresol, Prednilen, Urbason, Vériderm Médrol.

Section X: The indications, contra-indications, warnings, precautions…etc, of each class of the corticosteroids.

10.1 GlucocorticoidsCorticotropin (ACTH)CORTICOTROPIN INJECTION1-With 9 mg hydrolyzed gelatin.2-With 5 mg amino acetic acid.3-With 14 mg hydrolyzed gelatin.Administration and Dosage:Give IM or SC. May be given IV for diagnostic purposes.REPOSITORY CORTICOTROPIN INJECTIONAdministration and Dosage:Give IM or SC., and not for IV use.Indications: ACTH and cosyntropin: Diagnostic testing of adrenocortical function. Cosyntropin is

more potent and less allergenic than the exogenous ACTH preparations. ACTH: Corticotropin has limited therapeutic value in conditions responsive to

corticosteroid therapy; in such cases, corticosteroid therapy is the treatment of choice. Corticotropin may be used in the following disorders:

Endocrine: Nonsuppurative thyroiditis; hypercalcaemia associated with cancer.

Nervous system diseases: Acute exacerbations of multiple sclerosis. Miscellaneous: Tuberculosis meningitis with subarachnoid block or impending block

when accompanied by antituberculosis chemotherapy; trichinosis with neurologic or myocardial involvement; rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, and GI diseases in the same manner as the glucocorticoids.

Unlabeled uses: Treatment of infantile spasms. Administration and Dosage: Standard tests for verification of adrenal responsiveness to corticotropin may utilize

as much as 80 units as a single injection, or one or more injections of a lesser dosage. Perform verification tests prior to treatment with corticotrophins. The test should utilize the route(s) of administration proposed for treatment. Following verification, individualize dosage. Attempt only gradual change in dosage schedules after full drug effects have become apparent.

In the short test (single injection) for the ACTH stimulation test, a normal response is plasma cortisol > 20 mcg/dl on any sample. A blunted response indicates primary or secondary adrenal insufficiency. In the long test (8 hour infusion on 3 consecutive days), an absent or subnormal rise in plasma cortisol and 17-OHCS indicates primary adrenal failure. Plasma cortisol > 20 mcg/dl and a two- to threefold urinary 17-OHCS increase over baseline on day 4 indicate ACTH deficiency.

For diagnostic purposes: 10 to 25 units dissolved in 500 ml of 5% Dextrose Injection infused IV over 8 hours.

The usual IM or SC dose is 20 units 4 times daily. Chronic administration of > 40 units/day may be associated with uncontrollable adverse effects.

When indicated, reduce dosage gradually by increasing the duration between injections or decreasing the quantity of corticotropin injected or both.

Acute exacerbations of multiple sclerosis: 80 to 120 units/day IM for 2 to 3 weeks. Infantile spasms: 20 to 40 units daily or 80 units every other day IM for 3 months or

1 month after cessation of seizures has been recommended. Repository corticotropin injection: 40 to 80 units IM or SC every 24 to 72 hours.Preparation and storage: Reconstitute powder by dissolving in Sterile Water for Injection or Sodium Chloride Injection so that the individual dose will be contained in 1 to 2 ml of solution. Refrigerate reconstituted solution. Use within 24 hours.Actions:Pharmacology- Corticotropin (adrenocorticotropic hormone, ACTH) is secreted by the anterior pituitary and stimulates the adrenal cortex to produce and secrete adrenocortical hormones. Adequate adrenal function is necessary for corticotropin to elicit a pharmacological response. ACTH secretion is regulated by a negative feedback mechanism, whereby elevated plasma corticosteroid levels suppress ACTH secretion. Chronic administration of exogenous corticosteroids will decrease ACTH stores and induce morphological changes in the pituitary. In absence of ACTH stimulation, the adrenal cortex may atrophy.Cosyntropin is a synthetic peptide corresponding to the amino acid residues 1 to 24 of human ACTH, which exhibits the full corticosteroidogenic activity of natural ACTH. A dose of 0.25 mg cosyntropin is pharmacologically equivalent to 25 units of natural

ACTH. Cosyntropin is less allergenic than natural ACTH. Because it is unavailable in a repository form, it is not used therapeutically, only diagnostically.Pharmacokinetics - ACTH injection has a rapid onset. Plasma half-life is about 15 minutes. After IM or rapid IV administration of 25 units, peak plasma concentrations are usually achieved within 1 hour and begin to decrease after 2 to 4 hours. Repository corticotropin contains ACTH incorporated in a gelatin menstruum designed to delay the absorption rate and increase the period of effectiveness. Repository corticotropin has a slower onset but may sustain effects for up to 3 days.Contraindications:Scleroderma; osteoporosis; systemic fungal infections; ocular herpes simplex; recent surgery; history of or presence of peptic ulcer; congestive heart failure (CHF); hypertension; sensitivity to porcine proteins. IV administration (except in the treatment of idiopathic thrombocytopenic purpura). IV administration may be used for diagnostic testing of adrenocortical function. Treatment of conditions accompanied by primary adrenocortical insufficiency or adrenocortical hyperfunction.Warnings:Do not administer: Do not administer until adrenal responsiveness has been verified with the route of administration (IM or SC) which will be used during treatment. A rise in urinary and plasma corticosteroid values provides direct evidence of a stimulatory effect. Chronic administration: Chronic administration may lead to irreversible adverse

effects. ACTH may suppress signs and symptoms of chronic disease without altering the natural course of the disease. Since complications with corticotropin use are dependent on the dose and duration of treatment, a risk to benefit decision must be made in each case.

Prolonged use: Prolonged use increases the risk of hypersensitivity reactions and may produce posterior subcapsular cataracts and glaucoma with possible damage to the optic nerve.

Stress: Although the action of ACTH is similar to that of exogenous adrenocortical steroids, the quantity of adrenocorticoid secreted may be variable. In patients who receive prolonged corticotropin therapy, use additional rapidly acting corticosteroids before, during and after an unusually stressful situation.

Infection: ACTH may mask signs of infection including fungal or viral eye infections that may appear during its use. There may be decreased resistance and inability to localize infection. When infection is present, administer appropriate anti-infective therapy.

Tuberculosis - Observe patients with latent tuberculosis or tuberculin reactivity that receives ACTH, as reactivation of the disease may occur. During prolonged ACTH therapy, administer chemoprophylaxis.

Immunosuppression: Perform immunization procedures with caution, especially when high doses are administered, because of the possible hazards of neurological complications and lack of antibody response. Immunization with live vaccines is usually contraindicated in patients on ACTH or corticosteroid therapy.

Electrolytes: Corticotropin can elevate blood pressure, cause salt and water retention and increase potassium and calcium excretion. Dietary salt restriction and potassium supplementation may be necessary.

Hypersensitivity: Cosyntropin exhibits slight immunologic activity, does not contain foreign animal protein, and is less risky to use than natural ACTH. Most patients with a history of a previous hypersensitivity reaction to natural ACTH or a preexisting allergic disease will tolerate cosyntropin without incident; however, hypersensitivity reactions are possible. Refer to Management of Acute Hypersensitivity Reactions. (Reference)

Pregnancy: Category C. ACTH has embryocidal effects. Fetal abnormalities have been observed in animals. Use in pregnancy only when clearly needed and when potential benefits outweigh potential hazards to the fetus. Monitor infants born of mothers who have received substantial doses during pregnancy for signs of hyperadrenalism.

Lactation: It is not known whether this drug is excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants from ACTH, decide whether to discontinue nursing or to discontinue the drug.

Children: Prolonged use of corticotropin in children will inhibit skeletal growth. If use is necessary, give intermittently and carefully observe the child.

Precautions: Concomitant therapy: Since maximal corticotropin stimulation of the adrenals may

be limited during the first few days of treatment, administer a rapidly acting corticosteroid (e.g. hydrocortisone) when an immediate therapeutic effect is desirable.

Administer for treatment only when disease is intractable to more conventional therapy; ACTH should be adjunctive and not the sole therapy.

Use the lowest possible dose: Use the lowest possible dose to control the condition, and when reduction in dosage is possible, it should be gradual.

Sensitivity to porcine proteins: Perform skin testing prior to treatment in patients with suspected sensitivity to porcine proteins. During or following administration, observe for sensitivity reactions.

Adrenocortical insufficiency: Adrenocortical insufficiency induced by prolonged ACTH therapy may be minimized by gradual reduction of dosage. Insufficiency may persist for months after therapy discontinuation; therefore, in any situation of stress during that period, reinstitute corticosteroid therapy.

Hypothyroidism and cirrhosis: An enhanced effect of corticotropin may occur. Multiple sclerosis: Although ACTH may speed the resolution of acute exacerbations

of multiple sclerosis; it does not affect the ultimate outcome or natural course of the disease. Relatively high doses of ACTH are necessary to demonstrate a significant effect.

Acute gouty arthritis: Limit treatment of acute gouty arthritis to a few days. Since rebound attacks may occur when corticotropin is discontinued, administer conventional concomitant therapy during corticotropin treatment and for several days after it is stopped.

Mental disturbances: Psychic derangements may appear, ranging from euphoria, insomnia, mood swings, personality changes, and depression to frank psychosis. Existing emotional instability or psychotic tendencies may be aggravated.

Use with caution: Use with caution in patients with diabetes, abscess, pyogenic infections, diverticulitis, renal insufficiency and myasthenia gravis.

Drug abuse and dependence: Although drug dependence does not occur, sudden withdrawal of corticotropin after prolonged use may lead to recurrent symptoms, which make it difficult to stop. It may be necessary to taper the dose and increase the injection interval to gradually discontinue the medication.

Drug Interactions:

Corticotropin (ACTH) Drug Interactions

Precipitant drug Object drug DescriptionCorticotropin Amphotericin B Amphotericin B depletes potassium and may enhance

the potassium wasting effect of corticotropin; it may also decrease adrenocortical responsiveness to corticotropin. Closely monitor serum potassium.

Corticotropin Aspirin, indomethacin

Because of its known ulcerogenic effects, use aspirin cautiously in conjunction with corticotropin, especially in hypoprothrombinemia. Corticosteroids may increase the renal clearance of salicylates. Increased serum levels of salicylates and salicylate toxicity may occur when

steroid therapy is discontinued.

Corticotropin Insulin Increased requirements for insulin or oral hypoglycemic agents in diabetes have occurred in patients taking ACTH, due to the intrinsic hyperglycemic activity of glucocorticoids.

Corticotropin Diuretics Diuretics that deplete potassium may enhance the potassium wasting effect of corticotropin. Closely monitor serum potassium.

Drug/Lab test interactions: Corticotropin may decrease I131 uptake and may suppress reactions to skin tests. It may affect the method of Brown used for determination of urinary estradiol and estriol, causing falsely decreased concentrations of these estrogens. The drug may also interfere with colorimetric/fluorometric procedures for determination of urinary estrogens causing a falsely decreased concentration of urinary estrogens.

Adverse Reactions: Infections: Pneumonia, abscess and septic infection, and GI and GU infections

(more frequent with higher doses). Cardiovascular: Hypertension; CHF; necrotizing angiitis. CNS: Convulsions; vertigo; headache; increased intracranial pressure with

papilledema, pseudotumor cerebri, usually after treatment. Dermatologic: Impaired wound healing; petechiae and ecchymoses; increased

sweating; hyperpigmentation; thin fragile skin; facial erythema; acne; suppression of skin test reactions.

Electrolyte disturbances: Sodium and fluid retention; potassium and calcium loss; hypokalemic alkalosis.

Endocrine: Menstrual irregularities; suppression of growth in children; hirsutism; development of Cushingoid state; manifestations of latent diabetes mellitus; decreased carbohydrate tolerance; increased requirements for insulin or oral hypoglycemic agents in diabetics; secondary adrenocortical and pituitary unresponsiveness, especially during stress.

GI: Pancreatitis; ulcerative esophagitis; abdominal distention; peptic ulcer with possible perforation and hemorrhage has been associated with steroid therapy (this association has been disputed).

Hypersensitivity: Dizziness; nausea; vomiting; shock; skin reactions. Metabolic: Negative nitrogen balance due to protein catabolism. Musculoskeletal: Muscle weakness; steroid myopathy; loss of muscle mass;

osteoporosis; vertebral compression fractures; pathologic fracture of long bones; aseptic necrosis of femoral and humeral heads.

Ophthalmic: Posterior subcapsular cataracts; increased intraocular pressure; glaucoma with possible damage to optic nerve; exophthalmos.

Miscellaneous: Prolonged use may result in antibody production and subsequent loss of the stimulatory effect of ACTH.

Patient Information: ACTH may mask signs of infection. There may be decreased resistance and inability

to localize infection. Avoid immunizations with live vaccines. Diabetics may have increased requirements for insulin or oral hypoglycemics. Notify physician if marked fluid retention, muscle weakness, abdominal pain,

seizures, or headache occurs.

COSYNTROPIN1- With 10 mg mannitol.Administration and Dosage:Administer IM or IV as a rapid screening test of adrenal function. It may also be given as an IV infusion over 4 to 8 hours to provide a greater stimulus to the adrenal glands. Doses of 0.25 to 0.75 mg have been used and a maximal response noted with the smallest dose. The suggested dose is 0.25 mg dissolved in sterile saline injected IM. Children (less than or 2 years old): 0.125 mg will often suffice. IV infusion: Add 0.25 mg cosyntropin to dextrose or saline solutions and give at a

rate of approximately 0.04 mg/hour over 6 hours. For test procedure and interpretation of results, refer to manufacturer's insert.GlucocorticoidsIndications: Endocrine disorders: Primary or secondary adrenal cortical insufficiency

(hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids; in infancy, mineralocorticoid supplementation is important); congenital adrenal hyperplasia; nonsuppurative thyroiditis; hypercalcaemia associated with cancer).

Parenteral: Acute adrenal cortical insufficiency (hydrocortisone or cortisone is drug of choice); preoperatively or in serious trauma or illness with known adrenal insufficiency or when adrenal cortical reserve is doubtful; shock unresponsive to conventional therapy if adrenal cortical insufficiency exists or is suspected.

Rheumatic disorders: Adjunctive therapy for short-term use (acute episode or exacerbation) in: Ankylosing spondylitis; acute and subacute bursitis; acute nonspecific tenosynovitis; acute gouty arthritis; psoriatic arthritis; rheumatoid arthritis, including juvenile (selected cases may require low-dose maintenance therapy); posttraumatic osteoarthritis; synovitis of osteoarthritis; epicondylitis.

Collagen diseases: For exacerbation or maintenance therapy in selected cases of systemic lupus erythematosus, acute rheumatic carditis or systemic dermatomyositis (polymyositis).

Dermatologic diseases: Pemphigus; bullous dermatitis herpetiformis; severe erythema multiforme (Stevens-Johnson syndrome); mycosis fungoides; severe

psoriasis; angioedema or urticaria; exfoliative, severe seborrheic, contact or atopic dermatitis.

Allergic states: Control of severe or incapacitating allergic conditions intractable to conventional treatment in serum sickness and drug hypersensitivity reactions.

Parenteral therapy is indicated for urticarial transfusion reactions and acute noninfectious laryngeal edema (epinephrine is the drug of first choice).

Ophthalmic: 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; diffuse posterior uveitis and choroiditis; optic neuritis; sympathetic ophthalmia and anterior segment inflammation.

Respiratory diseases: Symptomatic sarcoidosis; bronchial asthma (including status asthmaticus); Loeffler's syndrome not manageable by other means; berylliosis; fulminating or disseminated pulmonary tuberculosis when accompanied by appropriate antituberculous chemotherapy; aspiration pneumonitis; seasonal or perennial allergic rhinitis.

Hematologic disorders: Idiopathic thrombocytopenic purpura and secondary thrombocytopenia in adults (IV only; IM use is contraindicated); acquired (autoimmune) hemolytic anemia; erythroblastopenia (RBC anemia); congenital (erythroid) hypoplastic anemia.

Neoplastic diseases: For palliative management of leukemias and lymphomas in adults and acute leukemia of childhood.

Edematous states: To induce diuresis or remission of proteinuria in the nephrotic syndrome (without uremia) of the idiopathic type or that due to lupus erythematosus.

GI diseases: To tied the patient over a critical period of the disease in ulcerative colitis, regional enteritis (Crohn's disease) and intractable sprue.

Nervous system: Acute exacerbations of multiple sclerosis (see Precautions). Miscellaneous: Tuberculous meningitis with subarachnoid block or impending block

when accompanied by appropriate antituberculous chemotherapy; in trichinosis with neurologic or myocardial involvement.

Intra-articular or soft tissue administration: Short-term adjunctive therapy (to tide the patient over an acute episode) in synovitis of osteoarthritis; rheumatoid arthritis; acute and subacute bursitis; acute gouty arthritis; epicondylitis; acute nonspecific tenosynovitis; post-traumatic osteoarthritis.Intralesional administration: Keloids; localized hypertrophic, infiltrated, inflammatory lesions of lichen planus, psoriatic plaques, granuloma annulare, lichen simplex chronicus (neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia areata. May be useful in cystic tumors of an aponeurosis or tendon (ganglia).Dexamethasone: Dexamethasone is also indicated for testing of adrenal cortical hyperfunction; cerebral edema associated with primary or metastatic brain tumor, craniotomy or head injury.Triamcinolone: Triamcinolone is also indicated for the treatment of pulmonary emphysema where bronchospasm or bronchial edema plays a significant role, and diffuse interstitial pulmonary fibrosis (Hamman-Rich syndrome); in conjunction with diuretic agents to induce a diuresis in refractory congestive heart failure (CHF) and in cirrhosis of the liver with refractory ascites; and for postoperative dental inflammatory reactions.

Administration and Dosage:The maximal activity of the adrenal cortex is between 2 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). Therefore, administer glucocorticoids in the morning prior to 9 am. When large doses are given, administer antacids between meals to help prevent peptic ulcers.Initiation of therapy: The initial dosage depends on the specific disease entity being treated. Maintain or adjust the initial dosage until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, discontinue the drug and transfer the patient to other appropriate therapy. It should be emphasized that dosage requirements are variable and must be individualized. For infants and children, the recommended dosage should be governed by the same considerations rather than by strict adherence to the ratio indicated by age or body weight.Maintenance therapy: After a favorable response is observed, determine the maintenance dosage by decreasing the initial dosage in small amounts at intervals until the lowest dosage that will maintain an adequate clinical response is reached. Constant monitoring of drug dosage is required. Situations which may make dosage adjustments necessary are changes in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stress; in this latter situation it may be necessary to increase the dosage for a period of time consistent with the patient's condition.Withdrawal of therapy: If, after long-term therapy, the drug is to be stopped, it must be withdrawn gradually. If spontaneous remission occurs in a chronic condition, discontinue treatment gradually. Continued supervision of the patient after discontinuation of corticosteroids is essential, since there may be a sudden reappearance of severe manifestations of the disease.Alternate day therapy: Alternate day therapy is a dosing regimen in which twice the usual daily dose is administered every other morning. The purpose is to provide the patient requiring long-term treatment with the beneficial effects of corticosteroids while minimizing pituitary-adrenal suppression, the cushingoid state, withdrawal symptoms and growth suppression in children. The benefits of alternate day therapy are only achieved by using the intermediate-acting agents.The rationale for this treatment schedule is based on two major premises: (a) The therapeutic effect of intermediate-acting corticosteroids persists longer than their physical presence and metabolic effects; (b) administration of the corticosteroid every other morning allows for reestablishment of a more normal hypothalamic-pituitary-adrenal (HPA) activity on the off-steroid day. Keep the following in mind when considering alternate day therapy:1-Benefits of alternate day therapy do not encourage indiscriminate steroid use.2-Alternate day therapy is primarily designed for patients in whom long-term corticosteroid therapy is anticipated.3-In less severe disease processes, it may be possible to initiate treatment with alternate day therapy. More severe disease states usually require daily divided high-dose therapy for initial control. Continue initial suppressive dose until satisfactory clinical response is obtained, usually 4 to 10 days in the case of many allergic and collagen diseases. Keep

the period of initial suppressive dose as brief as possible, particularly when alternate day therapy is intended. Once control is established, two courses are available: (a) Change to alternate day therapy, then gradually reduce the amount of corticosteroid given every other day or (b) reduce daily corticosteroid dose to the lowest effective level as rapidly as possible, 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 corticosteroids for long periods of time (eg, 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 such regular attempts be made. 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 controlled, attempt to reduce this dose to a minimum.5-Long-acting corticosteroids (eg, dexamethasone, betamethasone), due to their prolonged suppressive effect on adrenal activity, are not recommended for alternate day therapy.6-It is important to individualize therapy. 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 therapy to relieve symptoms may be added or increased at this time if needed.7-In the event of an acute flare-up of the disease process, it may be necessary to return to a full suppressive daily corticosteroid dose for control. Once control is established, alternate day therapy may be reinstituted.Intra-articular injection: Dose depends on the joint size and varies with the severity of the condition. In chronic cases, injections may be repeated at intervals of 1 to 5 or more weeks depending upon the degree of relief obtained from the initial injection. Injection must be made into the synovial space. Do not inject unstable joints. Repeated intra-articular injection may result in joint instability. X-ray follow-up is suggested in selected cases to detect deterioration.Suitable sites: Suitable sites for injection are the knee, ankle, wrist, elbow, shoulder, hip and phalangeal joints. Since difficulty is frequently encountered in entering the hip joint, avoid any large blood vessels in the area. Joints not suitable for injection are those that are anatomically inaccessible and devoid of synovial space such as the spinal joints and the sacroiliac joints. Treatment failures frequently result from failure to enter the joint space; little or no benefit follows injection into surrounding tissue. If failures occur when injections into the synovial spaces are certain, as determined by aspiration of fluid, repeated injections are usually of no benefit. Local therapy does not alter the underlying disease process; whenever possible, employ comprehensive therapy including physiotherapy and orthopedic correction. Miscellaneous (tendinitis, epicondylitis, ganglion): In the treatment of conditions such as tendinitis or tenosynovitis, inject into the tendon sheath rather than into the substance of the tendon. When treating conditions such as epicondylitis, outline the area of greatest tenderness and infiltrate the drug into the area. For ganglia of the tendon sheaths, inject the drug directly into the cyst. In many cases, a single injection markedly decreases size

of the cystic tumor and may affect disappearance. The dose varies with the condition being treated. In recurrent or chronic conditions, repeated injections may be needed.Injections for local effect in dermatologic conditions: Avoid injection of sufficient material to cause blanching, since this may be followed by a small slough. One to four injections are usually employed. Intervals between injections vary with the type of lesion being treated and duration of improvement produced by initial injection.Actions:Pharmacology - The naturally occurring adrenocortical steroids have both anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.These compounds, including hydrocortisone (cortisol) and cortisone, are used as replacement therapy in adrenocortical deficiency states and may be used for their anti-inflammatory effects. The synthetic steroid compounds prednisone, prednisolone and fludrocortisone also have both glucocorticoid and mineralocorticoid activity. Prednisone and prednisolone are used primarily for their glucocorticoid effects.In addition, a group of synthetic compounds with marked glucocorticoid activity are distinguished by the absence of any significant salt-retaining activity. These include triamcinolone, dexamethasone, methylprednisolone and betamethasone. These agents are used for their potent anti-inflammatory effects.

Pharmacokinetics: Absorption: Hydrocortisone and most of its congeners are readily absorbed from the

GI tract; greatly altered onsets and durations are usually achieved with injections of suspensions and esters.

Distribution: Hydrocortisone is reversibly bound to corticosteroid-binding globulin (CBG or transcortin) and corticosteroid binding albumin (CBA). Exogenous glucocorticoids are bound to these proteins to a significantly lesser degree. In hypoproteinemic or dysproteinemic states, the total endogenous hydrocortisone levels are decreased. Conversely, with increased CBG (pregnancy, estrogen therapy), the total plasma hydrocortisone levels are elevated. These alterations are not of clinical significance because it is the unbound fraction of the hormone that is metabolically active. However, the administration of exogenous glucocorticoids to patients with altered protein binding capacities will result in significant differences in glucocorticoid pharmacological effects.

Metabolism/Excretion: Hydrocortisone is metabolized by the liver, which is the rate-limiting step in its clearance. The metabolism and excretion of the synthetic glucocorticoids generally parallel hydrocortisone. Induction of hepatic enzymes will increase the metabolic clearance of hydrocortisone and the synthetic glucocorticoids. About 1% of its usual daily production, or about 200 mcg unchanged hormone is

excreted in urine daily. Renal clearance is increased when plasma levels are increased. Prednisone is inactive and must be metabolized to prednisolone. The following table summarizes the approximate dosage equivalencies (based on glucocorticoid properties) of the various glucocorticoid preparations and several of their pharmacokinetic parameters. The half-life values refer to the intrinsic activity of each agent; insoluble salts of these drugs are used as repository injections and have sustained effects due to delayed absorption from the injection site.

Contraindications:Systemic fungal infections; hypersensitivity to the drug; IM use in idiopathic thrombocytopenic purpura; administration of live virus vaccines (eg smallpox) in patients receiving immunosuppressive corticosteroid doses. Warnings: Infections: Corticosteroids may mask signs of infection, and new infections may

appear during their use. There may be decreased resistance and inability of the host defense mechanisms to prevent dissemination of the infection. If an infection occurs during therapy, it should be promptly controlled by suitable antimicrobial therapy.

1. Tuberculosis - Restrict use in active tuberculosis to cases of fulminating or disseminated disease in which the corticosteroid is used for disease management with appropriate chemotherapy. If corticosteroids are indicated in latent tuberculosis or tuberculin reactivity, observe closely; disease reactivation may occur. During prolonged corticosteroid use, these patients should receive chemoprophylaxis.

2. Fungal - Corticosteroids may exacerbate systemic fungal infections; do not use in such infections, except to control drug reactions due to amphotericin B. Concomitant use of amphotericin B and hydrocortisone has been followed by cardiac enlargement and CHF.

3. Amebiasis - Corticosteroids may activate latent amebiasis. Rule out amebiasis before giving to a patient who has been in the tropics or has unexplained diarrhea.

4. Cerebral malaria - A double-blind trial has shown corticosteroid use is associated with prolongation of coma and a higher incidence of pneumonia and GI bleeding.

5. Hepatitis: Although advocated for use in chronic active hepatitis, corticosteroids may be harmful in chronic active hepatitis positive for hepatitis B surface antigen.

Ocular effects: Prolonged use 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. Use cautiously in ocular herpes simplex because of possible corneal perforation.

Fluid and electrolyte balance: 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.

Peptic ulcer: The relationship between peptic ulceration and glucocorticoid therapy is unclear. Patients who appear to be at risk are those being treated for nephrotic syndrome or liver disease, or who are comatose postcraniotomy. Other predisposing factors include a total prednisone intake exceeding 1g, a history of ulcer disease,

concomitant use of known gastric irritants (as in arthritic patients) and stress. It may be desirable to use prophylactic antacids pending clarification of the relationship.

Immunosuppression: During therapy, do not use live virus vaccines (eg, smallpox). Do not immunize patients who are receiving corticosteroids, especially high doses, because of possible hazards of neurological complications and a lack of antibody response. This does not apply to patients receiving corticosteroids as replacement therapy. Corticosteroids may suppress reactions to skin tests.

Adrenal suppression: Prolonged therapy of pharmacologic doses may lead to hypothalamic-pituitary-adrenal suppression. The degree of adrenal suppression varies with the dosage, relative glucocorticoid activity, biological half-life and duration of glucocorticoid therapy within each individual. Adrenal suppression may be minimized by the use of intermediate-acting glucocorticoids (prednisone, prednisolone, methylprednisolone) on an alternate day schedule. Following prolonged therapy, abrupt discontinuation may result in a withdrawal syndrome without evidence of adrenal insufficiency. To minimize morbidity associated with adrenal insufficiency, discontinue exogenous corticosteroid therapy gradually. During withdrawal therapy, increased supplementation may be necessary during times of stress. Symptoms of adrenal insufficiency as a result of too rapid withdrawal include: Nausea; fatigue; anorexia; dyspnea; hypotension; hypoglycemia; myalgia; fever; malaise; arthralgia; dizziness; desquamation of skin; fainting. Continued supervision after therapy termination is essential; severe disease manifestations may reappear suddenly.

Stress: In patients receiving or recently withdrawn from corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids is indicated before, during and after stressful situations, except in patients on high-dose therapy. Relative adrenocortical insufficiency may persist for months after therapy ends; in any stress situation occurring during that period, reinstitute therapy. Since mineralocorticoid secretion may be impaired, administer salt or a mineralocorticoid concurrently.

Cardiovascular: Reports suggest an apparent association between corticosteroid use and left ventricular free wall rupture after a recent myocardial infarction. Use with great caution in these patients.

Hypersensitivity reactions: Anaphylactoid reactions have occurred rarely with corticosteroid therapy; take precautionary measures, especially in patients with a history of allergies. Refer to Management of Acute Hypersensitivity Reactions. (Reference)

Renal function impairment: Edema may occur in the presence of renal disease with a fixed or decreased glomerular filtration rate. Use with caution in renal insufficiency, acute glomerulonephritis and chronic nephritis.

Elderly: Consider the risk/benefit factors of steroid use. Consider lower doses because of body changes caused by aging (ie, diminution of muscle mass and plasma volume). Monitor blood pressure, blood glucose and electrolytes at least every 6 months.

Pregnancy: (Category C - Prednisolone sodium phosphate). Corticosteroids cross the placenta (prednisone has the poorest transport). In animal studies, large doses of cortisol administered early in pregnancy produced cleft palate, stillborn fetuses and

decreased fetal size. Chronic maternal ingestion during the first trimester has shown a 1% incidence of cleft palate in humans. If used in pregnancy, or in women of childbearing potential, weigh benefits against the potential hazards to the mother and fetus. Carefully observe infants born of mothers who have received substantial corticosteroid doses during pregnancy for signs of hypoadrenalism.

Lactation: Corticosteroids appear in breast milk and could suppress growth, interfere with endogenous corticosteroid production or cause other unwanted effects in the nursing infant. Advise mothers taking pharmacologic corticosteroid doses not to nurse. However, several studies suggest that amounts excreted in breast milk are negligible with prednisone or prednisolone doses <= 20 mg/day or methylprednisolone doses <= 8 mg/day, and large doses for short periods may not harm the infant. Alternatives to consider include waiting 3 to 4 hours after the dose before breastfeeding and using prednisolone rather than prednisone (resulting in a lower corticosteroid dose to the infant).

Children: Carefully observe growth and development of infants and children on prolonged corticosteroid therapy.

Benzyl alcohol: Some of these products contain benzyl alcohol, which has been associated with a fatal "gasping syndrome" in premature infants.

Precautions: Monitoring: Observe patients for weight increase, edema, hypertension, and

excessive potassium excretion, as well as for less obvious signs of adrenocortical steroid-induced untoward effects. Monitor for a negative nitrogen balance due to protein catabolism. A liberal protein intake is essential during prolonged therapy. Evaluate blood pressure and body weight, and do routine laboratory studies, including 2-hour postprandial blood glucose and serum potassium and a chest x-ray at regular intervals during prolonged therapy. Upper GI x-rays are desirable in patients with known or suspected peptic ulcer disease or significant dyspepsia or in patients complaining of gastric distress. Observe growth and development of infants and children on prolonged therapy.

Use the lowest possible dose: Make a benefit/risk decision in each individual case as to the size of the dose, duration of treatment and the use of daily or intermittent therapy, since complications of treatment are dependent on these factors.

Use with caution in: 1. GI - 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.

2. Cardiovascular - Hypertension; CHF; thromboembolitic tendencies; thrombophlebitis.

3. Miscellaneous - Osteoporosis; exanthema; Cushing's syndrome; antibiotic-resistant infections; convulsive disorders; metastatic carcinoma; myasthenia gravis; vaccinia; varicella; diabetes mellitus.; hypothyroidism, cirrhosis (enhanced effect of corticosteroids).

4. Steroid psychosis: Steroid psychosis is characterized by a delirious or toxic psychosis with clouded sensorium. Other symptoms may include euphoria, insomnia, mood swings, personality changes and severe depression. The onset of symptoms usually occurs within 15 to 30 days. Predisposing factors include doses > 40 mg prednisone equivalent, female predominance, and, possibly, a family history of psychiatric illness. A patient history of psychiatric problems does not correlate well with predisposition to steroid-induced psychosis. Incidence appears to correlate with dose. One study of 718 patients treated with prednisone revealed <= 40 mg/day = 1.3%; 41 to 80 mg/day = 4.6%; >= 80 mg/day = 18.4%. If the steroids cannot be discontinued, psychotropic medication is effective.

5. Multiple sclerosis: Although corticosteroids are effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not affect the ultimate outcome or natural history of the disease. Relatively high doses of corticosteroids are necessary to demonstrate a significant effect.

6. Repository injections: To minimize the likelihood and severity of atrophy, do not inject SC, avoid injection into the deltoid and avoid repeated IM injections into the same site, if possible. Repository injections are not recommended as initial therapy in acute situations.

7. Local injections: Intra-articular injection may produce systemic and local effects. A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever and malaise is suggestive of septic arthritis. Appropriate examination of any joint fluid present is necessary. If a diagnosis of sepsis is confirmed, institute appropriate antimicrobial therapy. Avoid local injection into an infected site and into unstable joints.

8. Strongly impress patients with the importance of not overusing joints in which symptomatic benefit has been obtained as long as the inflammatory process remains active. Frequent intra-articular injection may damage joint tissues.

9. Avoid overdistention of the joint capsule and deposition of steroid along the needle track in intra-articular injection, as it may lead to subcutaneous atrophy. While crystals of adrenal steroids in the dermis suppress inflammatory reactions, their presence may cause disintegration of the cellular elements and physiochemical changes in the ground substance of the connective tissue.

10. The resultant dermal or subdermal changes may form depressions in the skin at the injection site; the degree will vary with the amount of adrenal steroid injection. Regeneration is usually complete within a few months or after all crystals of the adrenal steroid has been absorbed. In order to minimize the incidence of dermal and subdermal atrophy, exercise care not to exceed recommended doses in injections. Make multiple small injections into the area of the lesion whenever possible.

11. Tartrazine sensitivity: Some of these products contain tartrazine, which may cause allergic-type reactions (including bronchial asthma) in susceptible individuals. Although the incidence of tartrazine sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. Specific products containing tartrazine are identified in the product listings.

12. Sulfite sensitivity: Some of these products contain sulfites which may cause severe allergic reactions in certain susceptible individuals, particularly asthmatics.

Anaphylactoid and hypersensitivity reactions have occurred. Do not use in patients allergic to sulfites. Products containing sulfites are identified in product listings.

Drug/Lab test interactions: Urine glucose and serum cholesterol levels may increase.Decreased serum levels of potassium, triiodothyronine (T3), and a minimal decrease of thyroxine (T4) may occur. Thyroid I131 uptake may be decreased. False-negative results with the nitroblue-tetrazolium test for bacterial infection. Dexamethasone, given for cerebral edema, may alter the results of a brain scan (decreased uptake of radioactive material).

Adverse Reactions: Parenteral therapy: Rare instances of blindness associated with intralesional

therapy around the face and head; hyperpigmentation or hypopigmentation; subcutaneous and cutaneous atrophy; sterile abscess; Charcot-like arthropathy; burning or tingling, especially in the perineal area (after IV injection); scarring, induration, inflammation, paresthesia, occasional irritation at the injection site or occasional brief increase in joint discomfort; transient or delayed pain or soreness; muscle twitching, ataxia, hiccoughs and nystagmus (low incidence following injection); anaphylactic reactions with or without circulatory collapse; cardiac arrest; bronchospasm; arachnoiditis after intrathecal use; foreign body granulomatous reactions involving the synovium with repeated injections.

Intra-articular: Osteonecrosis; tendon rupture; infection; skin atrophy; postinjection flare; hypersensitivity; facial flushing. Systemic reactions may also occur.

Intraspinal: Meningitis (tuberculous, bacterial, cryptococcal, aseptic, chemical); adhesive arachnoiditis; conus medullaris syndrome.

Cardiovascular: Thromboembolism or fat embolism; thrombophlebitis; necrotizing angiitis; cardiac arrhythmias or ECG changes due to potassium deficiency; syncopal episodes; aggravation of hypertension; myocardial rupture following recent MI (see Warnings). There are reports of cardiac arrhythmias, fatal arrest or circulatory collapse following the rapid administration of large IV doses of methylprednisolone (0.5 to 1 g in < 10 to 120 minutes). See Electrolyte Disturbances.

CNS: Convulsions; increased intracranial pressure with papilledema (pseudotumor cerebri), usually after stopping treatment; vertigo; headache; neuritis/paresthesias; aggravation of pre-existing psychiatric conditions; steroid psychoses.

Dermatologic: Impaired wound healing; thin fragile skin; petechiae and ecchymoses; erythema; lupus erythematosus-like lesions; suppression of skin test reactions; subcutaneous fat atrophy; purpura; striae; hirsutism; acneiform eruptions; other cutaneous reactions such as allergic dermatitis; urticaria; angioneurotic edema; perineal irritation.

Endocrine: Amenorrhea, postmenopausal bleeding and other menstrual irregularities; development of cushingoid state (eg, moonface, buffalo hump, supraclavicular fat pad enlargement, central obesity); suppression of growth in children; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress (eg, trauma, surgery, illness); increased sweating; decreased carbohydrate tolerance; hyperglycemia; glycosuria; increased insulin or sulfonylurea

requirements in diabetics; manifestations of latent diabetes mellitus; negative nitrogen balance due to protein catabolism; hirsutism.

Electrolyte disturbances: Sodium and fluid retention; hypokalemia; hypokalemic alkalosis; metabolic alkalosis; hypocalcemia; CHF in susceptible patients; hypotension or shock-like reactions; hypertension (see Warnings).

GI: Pancreatitis; abdominal distension; ulcerative esophagitis; nausea; vomiting; increased appetite and weight gain. Peptic ulcer with perforation and hemorrhage. Perforation of the small and large bowel, particularly in inflammatory bowel disease.

Musculoskeletal: Muscle weakness; steroid myopathy; muscle mass loss; tendon rupture; osteoporosis; aseptic necrosis of femoral and humeral heads (1% to 37%); spontaneous fractures, including vertebral compression fractures and pathologic fracture of long bones.

Ophthalmic: Posterior subcapsular cataracts; increased IOP; glaucoma; exophthalmos.

Miscellaneous: Anaphylactoid/hypersensitivity reactions, aggravation/masking of infections (see Warnings); malaise; leukocytosis (including neonates receiving dexamethasone via maternal injection); fatigue; insomnia; increased or decreased motility and number of spermatozoa.

Over dosage: Symptoms: There are two categories of toxic effects from therapeutic use of

glucocorticoids: Acute adrenal insufficiency: Acute adrenal insufficiency due to too rapid

corticosteroid withdrawal after long-term use resulting in fever, myalgia, arthralgia, malaise, anorexia, nausea, skin desquamation, orthostatic hypotension, dizziness, fainting, dyspnea and hypoglycemia.

Cushingoid changes: Cushingoid changes from continued use of large doses resulting in moonface, central obesity, striae, hirsutism, acne, ecchymoses, hypertension, osteoporosis, myopathy, sexual dysfunction, diabetes, hyperlipidemia, peptic ulcer, increased susceptibility to infection and electrolyte and fluid imbalance. Reports of acute toxicity or death are rare.

Treatment: Recovery of normal adrenal and pituitary function may require up to 9 months. Gradually taper the steroid under the supervision of a physician. Frequent lab tests are necessary. Supplementation is required during periods of stress (eg, illness, surgery, injury). Eventually reduce to the lowest dose that will control the symptoms or discontinue the corticosteroid completely. For large, acute overdoses, treatment includes gastric lavage or emesis and usual supportive measures.

Patient Information: May cause GI upset; take with meals or snacks. Take single daily or alternate day

doses in the morning prior to 9 am. Take multiple doses at evenly spaced intervals throughout the day.

Patients on chronic steroid therapy should wear or carry identification to that effect. Notify physician if unusual weight gain, swelling of the lower extremities, muscle

weakness, black tarry stools, vomiting of blood, puffing of the face, menstrual irregularities, prolonged sore throat, fever, cold or infection occurs.

Signs of adrenal insufficiency include fatigue, anorexia, nausea, vomiting, diarrhea, weight loss, weakness, dizziness and low blood sugar. Notify physician promptly if these symptoms occur following dosage reduction or withdrawal of therapy.

High dose or long-term therapy: Avoid abrupt withdrawal of therapy.

BETAMETHASONEAdministration and Dosage:Initial dosage: 0.6 to 7.2 mg/day.BETAMETHASONE SODIUM PHOSPHATE1-With EDTA, phenol and sodium bisulfite.Administration and Dosage:Betamethasone phosphate is highly soluble, has a prompt onset and may be given IV.Systemic and local: The initial dosage may vary up to 9 mg/day.BETAMETHASONE SODIUM PHOSPHATE AND BETAMETHASONE ACETATE1-With EDTA and benzalkonium chloride.Administration and Dosage:Betamethasone sodium phosphate provides prompt activity, while betamethasone acetate is only slightly soluble and affords sustained activity.Systemic: Not for IV use.Initial dose: 0.5 to 9 mg/day. Dosage ranges are 1/3 to 1/2 the oral dose given every 12 hours. In certain acute, life-threatening situations, dosages exceeding the usual may be justified and may be in multiples of oral dosage.Intrabursal, intra-articular, intradermal and intralesional: 1. Bursitis, tenosynovitis, and peritendinitis: 1 ml.2. Rheumatoid arthritis and osteoarthritis: 0.5 to 2 ml.3. Very large joints: 1 to 2 ml.4. Large joints: 1 ml.5. Medium joints: 0.5 to 1 ml.6. Small joints: 0.25 to 0.5 ml.7. Dermatologic conditions: 0.2 ml/cm2 intradermally.8. Maximum dose: 1 ml/week.9. Foot disorders: The following doses are recommended at 3 to 7 day intervals:10. Bursitis: Under heloma durum or heloma molle – 0.25 to 0.5 ml. Under calcaneal

spur – 0.5 ml. Over hallux rigidus or digiti quinti varus – 0.5 ml.11. Tenosynovitis, periostitis of cuboid: 0.5 ml.12. Acute gouty arthritis: 0.5 to 1 ml.

Corticosteroid Retention EnemasIndications:Adjunctive therapy in the treatment of ulcerative colitis, including ulcerative proctitis, ulcerative proctosigmoiditis and left-sided ulcerative colitis. It has proved useful in some cases involving the transverse and ascending colons.Actions:

Pharmacology - Hydrocortisone is partially absorbed following rectal administration. Ulcerative colitis patients have absorbed up to 50% of hydrocortisone administered by enema.Contraindications:Systemic fungal infections; ileocolostomy during immediate or early postoperative period.Warnings:If improvement fails to occur within 2 or 3 weeks, discontinue therapy. Symptomatic improvement may be misleading and should not be used as the sole criterion in judging efficacy. Sigmoidoscopic examination and x-ray visualization are essential for adequate monitoring.Precautions:Use with caution where there is a probability of impending perforation or abscess; pyogenic infections; intestinal anastomoses; obstruction; extensive fistulas and sinus tracts.Adverse Reactions:Local pain or burning; rectal bleeding; apparent exacerbations or sensitivity reactions.

HYDROCORTISONE RETENTION ENEMA1- In aqueous solution with carboxypolymethylene, polysorbate 80 and methylparaben.Administration and Dosage:Usual course of therapy is 100 mg nightly for 21 days, or until clinical and proctological remission occurs. Clinical symptoms usually subside in 3 to 5 days. Improvement in mucosal appearance may lag behind clinical improvement. Difficult cases may require 2 or 3 months of treatment. If therapy exceeds 21 days, discontinue gradually.Corticosteroid Intrarectal Foam

HYDROCORTISONE ACETATE INTRARECTAL FOAMIndications:Adjunctive therapy in the treatment of ulcerative proctitis of the distal portion of the rectum in patients who cannot retain corticosteroid enemas.Administration and Dosage:Usual dose is 1 applicatorful once or twice daily for 2 or 3 weeks, and every second day thereafter. Do not insert any part of the aerosol container into the anus. Satisfactory response usually occurs within 5 to 7 days. Sigmoidoscopy is recommended to judge dosage adjustment, duration of therapy and rate of improvement.Contraindications:Obstruction; abscess; perforation; peritonitis; recent intestinal anastomoses; extensive fistulas and sinus tracts.Warnings:Because the foam is not expelled, systemic hydrocortisone absorption may be greater than with corticosteroid enema formulations.

If no clinical or proctologic improvement occurs within 2 or 3 weeks, or if the patient's condition worsens, discontinue use.Administer with caution to patients with severe ulcerative disease because these patients are predisposed to perforation of the bowel wall.

CORTISONEAdministration and Dosage:The drug is insoluble in water.Initial dosage: 25 to 300 mg/day (oral). In less severe diseases, lower doses may suffice.

DEXAMETHASONEAdministration and Dosage:Initial dosage: 0.75 to 9 mg/day.Acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders: In acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders, the following dosage schedule combining parenteral and oral therapy (0.75 mg tablets) is suggested: Dexamethasone sodium phosphate injection, 4 mg/ml:First day: 1 or 2 ml IM.Second day: 4 tablets in 2 divided doses.Third day: 4 tablets in 2 divided doses.Fourth day: 2 tablets in 2 divided doses.Fifth day: 1 tablet.Sixth day: 1 tablet.Seventh day: No treatment.Eighth day: Follow-up visit.Suppression tests: For Cushing's syndrome: Give 1 mg at 11 pm. Draw blood for plasma cortisol determination the following day at 8 am. For greater accuracy, give 0.5 mg every 6 hours for 48 hours. Collect 24 hour urine to determine 17-hydroxycorticosteroid excretion.Test to distinguish Cushing's syndrome due to pituitary ACTH excess from Cushing's syndrome due to other causes: Give 2 mg every 6 hours for 48 hours. Collect 24 hour urine to determine 17-hydroxycorticosteroid excretion.Unlabeled uses: The dexamethasone suppression test has been used for the detection, diagnosis and management of depression; however, pending further evaluation and research, its value is unproven.

DEXAMETHASONE ACETATE1- With creatinine, polysorbate 80, carboxymethylcellulose, sodium bisulfite, EDTA, benzyl alcohol.Administration and Dosage:A long-acting repository preparation with prompt onset of action.Not for IV use.Systemic: 8 to 16 mg IM, may repeat in 1 to 3 weeks.Intralesional: 0.8 to 1.6 mg. Intra-articular and soft tissue: 4 to 16 mg; may repeat at 1 to 3 week intervals.

DEXAMETHASONE SODIUM PHOSPHATE1- With sodium sulfite and benzyl alcohol.2- With methyl and propyl parabens and sodium bisulfite.3- With sodium metabisulfite, EDTA and methyl and propyl parabens.4 - With EDTA, methyl and propyl parabens and sodium bisulfite.Administration and Dosage:Has a rapid onset and short duration of action compared to less soluble preparations.Systemic: Initial dosage: 0.5 to 9 mg daily. Usual dose ranges are 1/3 to 1/2 the oral dose given every 12 hours. However, in certain acute, life-threatening situations, dosages exceeding the usual may be justified and may be in multiples of the oral dosages.Cerebral edema: In adults, administer an initial IV dose of 10 mg, followed by 4 mg IM every 6 hours until maximum response has been noted. Response is usually noted within 12 to 24 hours. Dosage may be reduced after 2 to 4 days and gradually discontinued over 5 to 7 days. For palliative management of patients with recurrent or inoperable brain tumors, maintenance therapy with either the injection or tablets in a dosage of 2 mg 2 or 3 times daily may be effective.Unresponsive shock: Reported regimens range from 1 to 6 mg/kg as a single IV injection, to 40 mg initially followed by repeated IV injections every 2 to 6 hours while shock persists.Intra-articular, intralesional or soft tissue: Large joints: 2 to 4 mg.Small joints: 0.8 to 1 mg.Bursae: 2 to 3 mg.Tendon sheaths: 0.4 to 1 mg.Soft tissue infiltration: 2 to 6 mg.Ganglia: 1 to 2 mg.

DEXAMETHASONE SODIUM PHOSPHATE WITH LIDOCAINE HCl1- With EDTA, parabens and sodium bisulfite.Administration and Dosage:Dexamethasone sodium phosphate provides prompt activity. Lidocaine HCl is a local anesthetic with a rapid onset and a duration of 45 minutes to 1 hour (see Local Anesthetics). (Reference) Steroid activity usually begins by the time the anesthesia wears off.Soft tissue injection: Acute and subacute bursitis: 0.5 to 0.75 ml.Acute and subacute nonspecific tenosynovitis: 0.1 to 0.25 ml.

HYDROCORTISONE (Cortisol)Administration and Dosage:Cortisol suspension is insoluble in water.Initial dosage: 20 to 240 mg/day.

HYDROCORTISONE ACETATE

2-With 4 mg polysorbate 80, 5 mg sodium carboxymethylcellulose and 9 mg benzyl alcohol per ml.Administration and Dosage:Hydrocortisone acetate has a slow onset but long duration of action when compared with more soluble preparations. Because of its insolubility, it is suitable for intra-articular, intralesional and soft tissue injection where its anti-inflammatory effects are confined mainly to the area in which it has been injected, although it is capable of producing systemic hormonal effects.For intralesional, intra-articular or soft tissue injection only. Not for IV use.Large joints (e.g. knee): 25 mg; occasionally, 37.5 mg.Small joints (e.g. interphalangeal, temporomandibular): 10 to 25 mg.Tendon sheaths: 5 to 12.5 mg.Soft tissue infiltration: 25 to 50 mg; occasionally, 75 mg.Bursae: 25 to 37.5 mg.Ganglia: 12.5 to 25 mg.If desired, a local anesthetic may be injected before hydrocortisone acetate or mixed in a syringe and given simultaneously.If used prior to intra-articular injection of the steroid, inject most of the anesthetic into the soft tissues of the surrounding area and instill a small amount into the joint.If given together, mix in the injection syringe by drawing the steroid in first, then the anesthetic. In this way, the anesthetic will not be introduced inadvertently into the vial of the steroid. The mixture must be used immediately and any unused portion discarded.

HYDROCORTISONE CYPIONATEAdministration and Dosage:Initial dosage: 20 to 240 mg/day.

HYDROCORTISONE SODIUM PHOSPHATE1- With 3.2 mg sodium bisulfite, and 1.5 mg methylparaben and 0.2 mg propylparaben.Administration and Dosage:A water-soluble salt with a rapid onset but short duration of action.Administer by IV, IM or SC injection.Initial dosage: 15 to 240 mg/day. Usually, 1/3 to 1/2 the oral dose every 12 hours.Acute diseases: Doses higher than 240 mg may be required.HYDROCORTISONE SODIUM SUCCINATE1- With benzyl alcohol.Administration and Dosage:A water-soluble salt which is rapidly active.May be administered IV or IM. The initial dose is 100 to 500 mg, and may be repeated at 2, 4 or 6-hour intervals depending on patient response and clinical condition.

METHYLPREDNISOLONE1- With lactose and sucrose.Administration and Dosage:

Initial dose: 4 to 48 mg/day; adjust until a satisfactory response is noted. Individualize dosage. Determine maintenance dose by decreasing initial dose in small decrements at appropriate intervals until reaching the lowest effective dose.Dosepak 21 therapy: Follow manufacturer's directions.Alternate day therapy (ADT): Twice the usual dose is administered every other morning. The patient on long-term treatment receives the beneficial effects of corticosteroids while minimizing certain undesirable effects. In less severe diseases requiring long-term therapy, treatment may be initiated with ADT.

METHYLPREDNISOLONE ACETATE1- With polyethylene glycol and myristyl-gamma-picolinium chloride.Administration and Dosage:Because of its low solubility, methylprednisolone acetate has a sustained effect.Systemic: Not for IV use. As a temporary substitute for oral therapy, administer the total daily dose as a single IM injection. For prolonged effect, give a single weekly dose.Adrenogenital syndrome: A single 40 mg injection IM every 2 weeks.Rheumatoid arthritis: Weekly IM maintenance dose varies from 40 to 120 mg.Dermatologic lesions: 40 to 120 mg IM weekly for 1 to 4 weeks. In severe dermatitis (eg, poison ivy), relief may result within 8 to 12 hours of a single dose of 80 to 120 mg IM. In chronic contact dermatitis, repeated injections every 5 to 10 days may be necessary. In seborrheic dermatitis, a weekly dose of 80 mg IM may be adequate.Asthma and allergic rhinitis: 80 to 120 mg IM.Intra-articular and soft tissue: Large joints: 20 to 80 mg.Medium joints: 10 to 40 mg.Small joints: 4 to 10 mg.Ganglion, tendinitis, epicondylitis and bursitis: 4 to 30 mg.Intralesional: 20 to 60 mg.

METHYLPREDNISOLONE SODIUM SUCCINATE1-With sodium phosphate anhydrous (1.6 mg monobasic, 17.5 mg dibasic), 25 mg lactose and 9 mg benzyl alcohol.2-With sodium phosphate anhydrous (1.6 mg monobasic, 17.4 mg dibasic), » 18 mg benzyl alcohol.3-With sodium phosphate anhydrous (6.4 mg monobasic, 69.6 mg dibasic). May contain 36 to 70.2 mg benzyl alcohol.4-With sodium phosphate anhydrous (12.8 mg monobasic, 139.2 mg dibasic). May contain 66.8 to 141 mg benzyl alcohol.5-With sodium phosphate anhydrous (25.6 mg monobasic, 278 mg dibasic), 273 mg benzyl alcohol.Administration and Dosage:Highly soluble; has rapid effect by IV or IM routes.

Initial dose: 10 to 40 mg IV, administered over 1 to several minutes. Give subsequent doses IV or IM.Infants and children: Not less than 0.5mg/kg/24 hours.For high dose therapy, give 30 mg/kg IV, infused over 10 to 20 minutes. May repeat every 4 to 6 hours, not beyond 48 to 72 hours.

PREDNISOLONEAdministration and Dosage:Initial dosage: 5 to 60 mg/day.Multiple sclerosis: In treatment of acute exacerbations of multiple sclerosis, 200 mg daily for a week followed by 80 mg every other day for 1 month.

PREDNISOLONE ACETATE1- With polysorbate 80, carboxymethylcellulose and benzyl alcohol.Administration and Dosage:Relatively insoluble.Systemic: Not for IV use.Initial dosage: 4 to 60 mg/day, IM.Intralesional, intra-articular or soft tissue injection: 4 mg, up to 100 mg.Multiple sclerosis: 200 mg daily for a week, followed by 80 mg every other day or 4 to 8 mg dexamethasone every other day for 1 month.

PREDNISOLONE TEBUTATE1- With polysorbate 80, sorbitol and benzyl alcohol.Administration and Dosage:Slightly soluble with a slow onset and prolonged duration of action.Intra-articular, intralesional or soft tissue administration: Large joints: Large joints (eg, knee) – 20 mg; occasionally, 30 mg. Doses > 40 mg are not recommended.Small joints: Small joints (eg, interphalangeal, temporomandibular) - 8 to 10 mg. Bursae: 20 to 30 mg. Tendon sheaths: 4 to 10 mg. Ganglia: 10 to 20 mg.

PREDNISOLONE SODIUM PHOSPHATE1- With niacinamide, EDTA, phenol and sodium bisulfite.Administration and Dosage:Water soluble and rapid acting, but has a short duration of action.Prednisolone sodium phosphate oral liquid produces a 20% higher peak plasma level of prednisolone which occurs approximately 15 minutes earlier than the peak seen with tablet formulations.Parenteral: For IV or IM use.Initial dosage: 4 to 60 mg/day.

Intra-articular, intralesional or soft tissue administration: Large joints (eg, knee) : 10 to 20 mg.Small joints (eg, interphalangeal, temporomandibular): 4 to 5 mg.Bursae: 10 to 15 mg.Tendon sheaths: 2 to 5 mg.Soft tissue infiltration: 10 to 30 mg.Ganglia: 5 to 10 mg.Oral: Initial dosage - 5 to 60 ml (5 to 60 mg base) per day.Multiple sclerosis (acute exacerbations): 200 mg daily for a week, followed by 80 mg every other day or 4 to 8 mg dexamethasone every other day for 1 month.

PREDNISONEAdministration and Dosage:Initial dosage varies from 5 to 60 mg/day. Prednisone is inactive and must be metabolized to prednisolone. This may be impaired in patients with liver disease.

TRIAMCINOLONEAdministration and Dosage:Initial daily dosage in specific disorders is: Adrenocortical insufficiency: 4 to 12 mg, in addition to mineralocorticoid therapy.Rheumatic and dermatological disorders and bronchial asthma: 8 to 16 mg.Allergic states: 8 to 12 mg.Ophthalmological diseases: 12 to 40 mg.Respiratory diseases: 16 to 48 mg.Hematologic disorders: 16 to 60 mg.Tuberculous meningitis: 32 to 48 mg.Acute rheumatic carditis: 20 to 60 mg.Acute leukemia and lymphoma (adults): 16 to 40 mg. It may be necessary to give as much as 100 mg/day in leukemia.Acute leukemia (children): 1 to 2 mg/kg.Edematous states: 16 to 20 mg (up to 48 mg) until diuresis occurs.Systemic lupus erythematosus: 20 to 32 mg.

TRIAMCINOLONE ACETONIDE1-With polysorbate 80, carboxymethlcellulose and benzyl alcohol.Administration and Dosage:Relatively insoluble. Has an extended duration which may be permanent or sustained for several weeks.Systemic: Initial IM dose: 2.5 to 60 mg/day. Not for IV use.Intra-articular or intrabursal administration and for injection into tendon sheaths:

Initial dose: 2.5 to 5 mg for smaller joints and 5 to 15 mg for larger joints. For adults, doses up to 10 mg for smaller areas and up to 40 mg for larger areas are usually sufficient.Intradermal: Use only 3 mg/ml or 10 mg/ml. Initial dose varies; limit to 1 mg per site.Clumping results from exposure to freezing temperatures; do not use.

TRIAMCINOLONE DIACETATE1-With polysorbate 80, polyethylene glycol and benzyl alcohol.Administration and Dosage:Slightly soluble providing a prompt onset of action and a longer duration of effect.Systemic: Not for IV use. May be administered IM for initial therapy; however, most clinicians prefer to adjust the dose orally until adequate control is attained. The average dose is 40 mg IM per week. In general, a single parenteral dose 4 to 7 times the oral daily dose controls the patient from 4 to 7 days, up to 3 to 4 weeks.Intra-articular and intrasynovial: 5 to 40 mg.Intralesional or sublesional: 5 to 48 mg. Do not use more than 12.5 mg per injection site. The usual average dose is 25 mg per lesion.

TRIAMCINOLONE HEXACETONIDE1- With polysorbate 80, sorbitol and benzyl alcohol.Administration and Dosage:Relatively insoluble, slowly absorbed and has a prolonged action. Not for IV use.Intra-articular: 2 to 20 mg average.Large joints (eg, knee, hip, shoulder): 10 to 20 mg.Small joints (eg, interphalangeal, metacarpophalangeal): 2 to 6 mg. Intralesional or sublesional: Up to 0.5 mg per square inch of affected area.

10.1 MineralocorticoidsFLUDROCORTISONE ACETATEIndications: Partial replacement therapy for primary and secondary adrenocortical insufficiency in

Addison's disease and for the treatment of salt-losing adrenogenital syndrome. Unlabeled uses: Fludrocortisone 100 to 400 mcg/day has been used in the

management of severe orthostatic hypotension. Administration and Dosage: Addison's disease: The usual dose is 0.1 mg/day (range 0.1 mg 3 times a week to 0.2

mg/day). If transient hypertension develops as a consequence of therapy, reduce the dose to 0.05 mg/day. Administration in conjunction with cortisone (10 to 37.5 mg/day) or hydrocortisone (10 to 30 mg/day) is preferable.

Children and adults: Another recommended dose is 0.05 to 0.1 mg/24 hours. Infants: A recommended dose is 0.1 to 0.2 mg/24 hours. Salt-losing adrenogenital syndrome: 0.1 to 0.2 mg/day.Actions:

Pharmacology - Fludrocortisone is an adrenal cortical steroid with potent mineralocorticoid activity and high glucocorticoid activity (about 15 times as potent as hydrocortisone), but is used only for its mineralocorticoid effects. Mechanism: Mineralocorticoids act on the renal distal tubules to enhance the reabsorption of sodium. They increase urinary excretion of both potassium and hydrogen ions. The consequence of these three primary effects together with similar actions on cation transport in other tissues appears to account for the spectrum of physiological activities characteristic of mineralocorticoids.In small oral doses, fludrocortisone produces marked sodium retention and increased urinary potassium excretion. It also causes a rise in blood pressure, apparently because of these effects on electrolyte levels. In larger doses, fludrocortisone inhibits endogenous adrenal cortical secretion, thymic activity, and pituitary corticotropin excretion, it promotes the deposition of liver glycogen, and, unless protein intake is adequate, it induces negative nitrogen balance.Pharmacokinetics - Fludrocortisone is readily absorbed from the GI tract with peak concentrations in 1.7 hours. Plasma half-life is approximately 3.5 hours, but biological half-life ranges from 18 to 36 hours.Contraindications:Hypersensitivity to fludrocortisone; systemic fungal infections.Warnings:Supplemental measures: Use mineralocorticoid therapy preferably in conjunction with other supplemental measures (eg, glucocorticoids, control of electrolytes, control of infection).Adrenal insufficiency: To avoid drug-induced adrenal insufficiency, supportive dosage may be required in times of stress (eg, trauma, surgery, severe illness), both during treatment with fludrocortisone and for a year afterwards.Pregnancy: Category C. Safety for use during pregnancy has not been established. Use only when clearly needed and when the potential benefits outweigh the potential hazards to the fetus. If it is necessary to give steroids during pregnancy, observe the newborn infant for signs of adrenocortical insufficiency and institute appropriate therapy, if necessary.Lactation: Corticosteroids are found in the breast milk of lactating women. Exercise caution when administering to nursing women.Children: Safety and efficacy for use in children have not been established. Monitor growth and development of infants and children on prolonged therapy.Precautions:Addison's disease: Patients with Addison's disease are more sensitive to the action of the hormone and may exhibit side effects in an exaggerated degree. Closely monitor patients and stop treatment if a significant increase in weight or blood pressure, edema or cardiac enlargement occurs.Sodium retention and potassium loss: Sodium retention and potassium loss are accelerated by a high sodium intake. If edema occurs, restrict dietary sodium. Perform frequent blood electrolyte determinations; potassium supplementation may be necessary.Infection: Monitor patients for evidence of intercurrent infection. Should this occur, initiate appropriate anti-infective therapy.Adverse Reactions:

Side effects may occur if dosage is too high or prolonged or if withdrawal is too rapid. Because it possesses glucocorticoid activity, fludrocortisone may cause side effects similar to those of the glucocorticoids. Cardiovascular: Edema; hypertension; CHF; enlargement of the heart.Dermatologic: Bruising; increased sweating; hives or allergic skin rash.Miscellaneous: Hypokalemic alkalosis.Overdosage: Symptoms: Hypertension; edema; hypokalemia; excessive weight gain; increase in

heart size. Treatment: Discontinue the drug; symptoms usually subside within several days.

Resume subsequent treatment with reduced doses. Muscular weakness may develop due to excessive potassium loss; treat with potassium supplements. Monitor blood pressure and serum electrolytes regularly.

Patient Information: Notify physician if dizziness, severe or continuing headaches, swelling of feet or

lower legs, or unusual weight gain occurs