Use with caution in patients with hyperthyroidism, cirrhosis, nonspecific ulcerative colitis, hypertension, osteoporosis, thromboembolic tendencies, CHF, convulsive disorders, myasthenia gravis, thrombophlebitis, peptic ulcer, diabetes, glaucoma, cataracts, or tuberculosis. Use caution in hepatic impairment.

May cause HPA axis suppression. Acute adrenal insufficiency may occur with abrupt withdrawal after long-term therapy or with stress; young pediatric patients may be more susceptible to adrenal axis suppression from topical therapy. Avoid use of topical preparations with occlusive dressings or on weeping or exudative lesions.

Because of the risk of adverse effects, systemic corticosteroids should be used cautiously in the elderly, in the smallest possible dose, and for the shortest possible time

Systemic:

>10%:

Central nervous system: Insomnia, nervousness

Gastrointestinal: Increased appetite, indigestion

1% to 10%:

Dermatologic: Hirsutism

Endocrine & metabolic: Diabetes mellitus

Neuromuscular & skeletal: Arthralgia

Ocular: Cataracts

Respiratory: Epistaxis

<1%: Hypertension, edema, euphoria, headache, delirium, hallucinations, seizure, mood swings, acne, dermatitis, skin atrophy, bruising, hyperpigmentation, hypokalemia, hyperglycemia, Cushing's syndrome, sodium and water retention, bone growth suppression, amenorrhea, peptic ulcer, abdominal distention, ulcerative esophagitis, pancreatitis, muscle wasting, hypersensitivity reactions, immunosuppression

Topical:

>10%: Dermatologic: Eczema (12.5%)

1% to 10%: Dermatologic: Pruritus (6%), stinging (2%), dry skin (2%)

<1%: Allergic contact dermatitis, burning, dermal atrophy, folliculitis, HPA axis suppression, hypopigmentation; metabolic effects (hyperglycemia, hypokalemia); striae

Decreased effect:

Insulin decreases hypoglycemic effect

Phenytoin, phenobarbital, ephedrine, and rifampin increase metabolism of hydrocortisone and decrease steroid blood level

Increased toxicity:

Oral anticoagulants change prothrombin time

Potassium-depleting diuretics increase risk of hypokalemia

Cardiac glucosides increase risk of arrhythmias or digitalis toxicity secondary to hypokalemia

Ethanol: Avoid ethanol (may enhance gastric mucosal irritation).

Food: Hydrocortisone interferes with calcium absorption.

Herb/Nutraceutical: St John's wort may decrease hydrocortisone levels. Avoid cat's claw, echinacea (have immunostimulant properties).

Sodium succinate: Reconstitute 100 mg vials with bacteriostatic water (not >2 mL). Act-O-Vial (self-contained powder for injection plus diluent) may be reconstituted by pressing the activator to force diluent into the powder compartment. Following gentle agitation, solution may be withdrawn via syringe through a needle inserted into the center of the stopper. May be administered (I.V. or I.M.) without further dilution. After initial reconstitution, hydrocortisone sodium succinate solutions are stable for 3 days at room temperature or under refrigeration when protected from light. Stability of parenteral admixture (Solu-Cortef®) at room temperature (25°C) and at refrigeration temperature (4°C) is concentration-dependent:

Stability of concentration 1 mg/mL: 24 hours

Stability of concentration 2 mg/mL to 60 mg/mL: At least 4 hours

Solutions for I.V. infusion: Reconstituted solutions may be added to an appropriate volume of compatible solution for infusion. Concentration should generally not exceed 1 mg/mL. However, in cases where administration of a small volume of fluid is desirable, 100-3000 mg may be added to 50 mL of D5W or NS (stability limited to 4 hours).

Hydrocortisone sodium phosphate: Stable in D5W, NS, fat emulsion 10%

Y-site administration: Compatible: Allopurinol, amifostine, aztreonam, cefepime, cladribine, clarithromycin, docetaxel, etoposide, famotidine, filgrastim, fluconazole, fludarabine, gemcitabine, granisetron, melphalan, ondansetron, paclitaxel, piperacillin/tazobactam, teniposide, thiotepa, vinorelbine. Incompatible: Sargramostim

Compatibility in syringe: Compatible: Metoclopramide. Incompatible: Doxapram

Compatibility when admixed: Compatible: Amikacin, amphotericin B, amphotericin B with heparin, bleomycin, dacarbazine, metaraminol, sodium bicarbonate, verapamil. Variable (consult detailed reference): Mitoxantrone

Hydrocortisone sodium succinate: Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D5¹/4NS, D5¹/2NS, D5NS, D5W, D10W, D20W, LR, ¹/2NS, NS, fat emulsion 10%

Y-site administration: Compatible: Acyclovir, allopurinol, amifostine, aminophylline, amphotericin B cholesteryl sulfate complex, ampicillin, amsacrine, atracurium, atropine, aztreonam, betamethasone sodium phosphate, calcium gluconate, cefepime, chlordiazepoxide, chlorpromazine, cisatracurium, cladribine, cyanocobalamin, cytarabine, dexamethasone sodium phosphate, digoxin, diphenhydramine, docetaxel, dopamine, doxorubicin liposome, droperidol, droperidol and fentanyl, edrophonium, enalaprilat, epinephrine, esmolol, estrogens (conjugated), ethacrynate sodium, etoposide, famotidine, fentanyl, filgrastim, fludarabine, fluorouracil, foscarnet, furosemide, gatifloxacin, gemcitabine, granisetron, heparin, hydralazine, inamrinone, insulin (regular), isoproterenol, kanamycin, lidocaine, linezolid, lorazepam, magnesium sulfate, melphalan, menadiol sodium diphosphate, meperidine, methoxamine, methylergonovine, minocycline, morphine, neostigmine, norepinephrine, ondansetron, oxacillin, oxytocin, paclitaxel, pancuronium, penicillin G potassium, pentazocine, phytonadione, piperacillin/tazobactam, procainamide, prochlorperazine edisylate, propofol, propranolol, pyridostigmine, remifentanil, scopolamine, sodium bicarbonate, succinylcholine, tacrolimus, teniposide, theophylline, thiotepa, trimethaphan camsylate, trimethobenzamide, vecuronium, vinorelbine. Incompatible: Ciprofloxacin, diazepam, ergotamine, idarubicin, midazolam, phenytoin, sargramostim. Variable (consult detailed reference): Diltiazem, methylprednisolone sodium succinate, promethazine

Compatibility in syringe: Compatible: Diatrizoate meglumine 52%, diatrizoate sodium 8%, diatrizoate sodium 60%, iohexol, iopamidol, iothalamate meglumine 60%, ioxaglate meglumine 39.3%, ioxaglate sodium 19.6%, metoclopramide, thiopental. Incompatible: Doxapram

Compatibility when admixed: Compatible: Amikacin, aminophylline, amphotericin B, calcium chloride, calcium gluconate, chloramphenicol, clindamycin, corticotropin, daunorubicin, diphenhydramine, dopamine, erythromycin lactobionate, floxacillin, lidocaine, magnesium sulfate, mephentermine, metronidazole, metronidazole with sodium bicarbonate, mitomycin, mitoxantrone, norepinephrine, penicillin G potassium, penicillin G sodium, piperacillin, polymyxin B sulfate, potassium chloride, procaine, sodium bicarbonate, theophylline, thiopental, vancomycin, verapamil, vitamin B complex with C. Incompatible: Aminophylline with cephalothin, bleomycin, colistimethate, ephedrine, hydralazine, nafcillin, pentobarbital, phenobarbital, prochlorperazine edisylate, promethazine. Variable (consult detailed reference): Amobarbital, ampicillin, cytarabine, dimenhydrinate, furosemide, heparin, kanamycin, metaraminol

Onset of action:

Hydrocortisone acetate: Slow

Hydrocortisone sodium succinate (water soluble): Rapid

Duration: Hydrocortisone acetate: Long

Absorption: Rapid by all routes, except rectally

Metabolism: Hepatic

Half-life elimination: Biologic: 8-12 hours

Excretion: Urine (primarily as 17-hydroxysteroids and 17-ketosteroids)

Acute adrenal insufficiency: I.M., I.V.:

Infants and young Children: Succinate: 1-2 mg/kg/dose bolus, then 25-150 mg/day in divided doses every 6-8 hours

Older Children: Succinate: 1-2 mg/kg bolus then 150-250 mg/day in divided doses every 6-8 hours

Adults: Succinate: 100 mg I.V. bolus, then 300 mg/day in divided doses every 8 hours or as a continuous infusion for 48 hours; once patient is stable change to oral, 50 mg every 8 hours for 6 doses, then taper to 30-50 mg/day in divided doses

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

Anti-inflammatory or immunosuppressive:

Infants and Children:

Oral: 2.5-10 mg/kg/day or 75-300 mg/m²/day every 6-8 hours

I.M., I.V.: Succinate: 1-5 mg/kg/day or 30-150 mg/m²/day divided every 12-24 hours

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

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

Physiologic replacement: Children:

Oral: 0.5-0.75 mg/kg/day or 20-25 mg/m²/day every 8 hours

I.M.: Succinate: 0.25-0.35 mg/kg/day or 12-15 mg/m²/day once daily

Shock: I.M., I.V.: Succinate:

Children: Initial: 50 mg/kg, then repeated in 4 hours and/or every 24 hours as needed

Adolescents and Adults: 500 mg to 2 g every 2-6 hours

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

Adults:

Rheumatic diseases:

Intralesional, intra-articular, soft tissue injection: Acetate:

Large joints: 25 mg (up to 37.5 mg)

Small joints: 10-25 mg

Tendon sheaths: 5-12.5 mg

Soft tissue infiltration: 25-50 mg (up to 75 mg)

Bursae: 25-37.5 mg

Ganglia: 12.5-25 mg

Stress dosing (surgery) in patients known to be adrenally-suppressed or on chronic systemic steroids: I.V.:

Minor stress (ie, inguinal herniorrhaphy): 25 mg/day for 1 day

Moderate stress (ie, joint replacement, cholecystectomy): 50-75 mg/day (25 mg every 8-12 hours) for 1-2 days

Major stress (pancreatoduodenectomy, esophagogastrectomy, cardiac surgery): 100-150 mg/day (50 mg every 8-12 hours) for 2-3 days

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

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

Oral: Administer with food or milk to decrease GI upset

Parenteral: Hydrocortisone sodium succinate may be administered by I.M. or I.V. routes

I.V. bolus: Dilute to 50 mg/mL and administer over 30 seconds to several minutes (depending on the dose)

I.V. intermittent infusion: Dilute to 1 mg/mL and administer over 20-30 minutes

Topical: Apply a thin film to clean, dry skin and rub in gently

Topical: Before applying, wash area gently and thoroughly. Apply a thin film to cleansed area and rub in gently until medication vanishes. Avoid use of occlusive dressings over topical application unless directed by a physician. Avoid use on weeping or exudative lesions. Avoid exposing affected area to sunlight; you will be more sensitive and severe sunburn may occur. Consult prescriber if breast-feeding.

Rectal: Gently insert suppository as high as possible with gloved finger while lying down. Avoid injury with long or sharp fingernails. Remain in resting position for 10 minutes after insertion.

Neuromuscular Effects: ICU-acquired paresis was recently studied in 5 ICUs (3 medical and 2 surgical ICUs) at 4 French hospitals. All ICU patients without pre-existing neuromuscular disease admitted from March 1999 through June 2000 were evaluated (De Jonghe B, 2002). Each patient had to be mechanically ventilated for 7 days and was screened daily for awakening. The first day the patient was considered awake was Study Day 1. Patients with severe muscle weakness on Study Day 7 were considered to have ICU-acquired paresis. Among the 95 patients who were evaluable, about 25% developed ICU-acquired paresis. Independent predictors included: female gender, the number of days with 2 organ dysfunction, and administration of corticosteroids. Further studies may be required to verify and characterize the association between the development of ICU-acquired paresis and use of corticosteroids. Concurrent use of a corticosteroid and muscle relaxant appear to increase the risk of certain ICU myopathies; avoid or administer the corticosteroid at the lowest dose possible.

Adrenal Insufficiency: Patients will often have steroid-induced adverse effects on glucose tolerance and lipid profiles. When discontinuing steroid therapy in patients on long-term steroid supplementation, it is important that the steroid therapy be discontinued gradually. Abrupt withdrawal may result in adrenal insufficiency with hypotension and hyperkalemia. Patients on long-term steroid supplementation will require higher corticosteroid doses when subject to stress (ie, trauma, surgery, severe infection). Guidelines for glucocorticoid replacement during various surgical procedures has been published (Salem M, 1994, Coursin DB, 2002).

Septic Shock: A recent randomized, double-blind, placebo controlled trial assessed whether low dose corticosteroid administration could improve 28-day survival in patients with septic shock and relative adrenal insufficiency. Relative adrenal insufficiency was defined as an inappropriate response to corticotropin administration (increase of serum cortisol of 9 mcg/dL from baseline). Cortisol levels were drawn immediately before corticotropin administration and 30 to 60 minutes afterwards. Three hundred adult septic shock patients requiring mechanical ventilation and vasopressor support were randomized to either hydrocortisone (50 mg IVP every 6 hours) and fludrocortisone (50 mcg tablet daily via nasogastric tube) or matching placebos for 7 days. In patients who did not appropriately respond to corticotropin (nonresponders), there were significantly fewer deaths in the active treatment group. Vasopressor therapy was withdrawn more frequently in this subset of the active treatment group. Adverse events were similar in both groups. Patients who lack adrenal reserve and thus have relative adrenal insufficiency during the stress of septic shock may benefit from physiologic steroid replacement. However, there was a trend for increased mortality in patients who responded to the corticotropin test (increase serum cortisol >9 mcg/dL from baseline). These patients may not benefit from physiologic steroid replacement. Further study is required to better characterize the patient populations who may benefit.

Oral and intravenous steroid therapy in patients with heart failure should be administered cautiously with special attention given to signs and symptoms of fluid retention.

Aerosol, rectal, as acetate (Cortifoam®): 10% (15 g) [90 mg/applicator]

Cream, rectal, as acetate (Nupercainal® Hydrocortisone Cream): 1% (30 g) [strength expressed as base]

Cream, rectal, as base:

Cortizone®-10: 1% (30g) [contains aloe]

Preparation H® Hydrocortisone: 1% (27 g)

Cream, topical, as acetate: 0.5% (9 g, 30 g, 60 g) [available with aloe]; 1% (30 g, 454 g) [available with aloe]

Cream, topical, as base: 0.5% (30 g); 1% (1.5 g, 30 g, 114 g, 454 g); 2.5% (20 g, 30 g, 454 g)

Anusol-HC®: 2.5% (30 g) [contains benzyl alcohol]

Caldecort®: 1% (30 g) [contains aloe vera gel]

Cortaid® Intensive Therapy: 1% (60 g)

Cortaid® Maximum Strength: 1% (15 g, 30 g, 40 g, 60 g) [contains aloe vera gel and benzyl alcohol]

Cortaid® Sensitive Skin: 0.5% (15 g) [contains aloe vera gel]

Cortizone®-10 Maximum Strength: 1% (15 g, 30 g, 60 g) [contains aloe]

Cortizone®-10 Plus Maximum Strength: 1% (30 g, 60 g) [contains vitamins A, D, E and aloe]

Dermarest® Dri-Cort: 1% (15 g, 30 g)

HydroZone Plus, Proctocort®, Procto-Pak™: 1% (30 g)

Hytone®: 2.5% (30 g, 60 g)

IvySoothe™: 1% (30 g) [contains aloe]

Post Peel Healing Balm: 1% (23 g)

ProctoCream® HC: 2.5% (30 g) [contains benzyl alcohol]

Procto-Kit™: 1% (30 g) [packaged with applicator tips and finger cots]; 2.5% (30g) [packaged with applicator tips and finger cots]

Proctosol-HC®, Proctozone-HC™: 2.5% (30 g)

Summer's Eve® SpecialCare™ Medicated Anti-Itch Cream: 1% (30 g)

Cream, topical, as butyrate (Locoid®, Locoid Lipocream®): 0.1% (15 g, 45 g)

Cream, topical, as probutate (Pandel®): 0.1% (15 g, 45 g, 80 g)

Cream, topical, as valerate (Westcort®): 0.2% (15 g, 45 g, 60 g)

Gel, topical, as base:

Corticool®: 1% (45 g)

Cortagel® Maximum Strength: 1% (15 g, 30 g) [contains aloe vera gel] [DSC]

Injection, powder for reconstitution, as sodium succinate (Solu-Cortef®): 100 mg, 250 mg, 500 mg, 1 g [diluent contains benzyl alcohol; strength expressed as base]

Lotion, topical, as base: 1% (120 mL); 2.5% (60 mL)

Aquanil™ HC: 1% (120 mL)

Beta-HC®, Cetacort®, Sarnol®-HC: 1% (60 mL)

HydroZone Plus: 1% (120 mL)

Hytone®: 2.5% (60 mL)

LactiCare-HC®: 1% (120 mL); 2.5% (60 mL, 120 mL) [DSC]

Nutracort®: 1% (60 mL, 120 mL); 2.5% (60 mL, 120 mL)

Ointment, topical, as acetate: 1% (30 g) [strength expressed as base; available with aloe]

Anusol® HC-1: 1% (21 g) [strength expressed as base]

Cortaid® Maximum Strength: 1% (15 g, 30 g) [strength expressed as base]

Ointment, topical, as base: 0.5% (30 g); 1% (30 g, 454 g); 2.5% (20 g, 30 g, 454 g)

Cortizone®-10 Maximum Strength: 1% (30 g, 60 g)

Hytone®: 2.5% (30 g)

Ointment, topical, as butyrate (Locoid®): 0.1% (15 g, 45 g)

Ointment, topical, as valerate (Westcort®): 0.2% (15 g, 45 g, 60 g)

Solution, otic, as base (EarSol® HC): 1% (30 mL) [contains alcohol 44%, benzyl benzoate, yerba santa]

Solution, topical, as base (Texacort®): 2.5% (30 mL) [contains alcohol]

Solution, topical, as butyrate (Locoid®): 0.1% (20 mL, 60 mL) [contains alcohol 50%]

Solution, topical spray, as base:

Cortaid® Intensive Therapy: 1% (60 mL) [contains alcohol]

Cortizone® 10 Quick Shot: 1% (44 mL) [contains benzyl alcohol]

Dermtex® HC: 1% (52 mL) [contains menthol 1%]

Suppository, rectal, as acetate: 25 mg (12s, 24s, 100s)

Anucort™ HC: 25 mg (12s, 24s, 100s)

Anusol-HC®, Proctosol-HC®: 25 mg (12s, 24s)

Encort™: 30 mg (12s)

Hemril®-30, Proctocort®, Proctosert: 30 mg (12s, 24s)

Suspension, rectal, as base: 100 mg/60 mL (7s)

Colocort®: 100 mg/60 mL (1s, 7s)

Tablet, as base: 20 mg

Cortef®: 5 mg, 10 mg, 20 mg

Hydrocortone®: 10 mg [DSC]

Abraham E and Evans T, "Corticosteroids and Septic Shock [editorial],"JAMA, 2002, 288(7):886-7.

Annane D, Sebille V, Charpentier C, et al, "Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock,"JAMA, 2002, 288(7):862-71.

Cooper MS and Stewart PM, "Corticosteroid Insufficiency in Acutely Ill Patients,"N Engl J Med, 2003, 348(8):727-34.

Coursin DB and Wood KE, "Corticosteroid Supplementation for Adrenal Insufficiency,"JAMA, 2002, 287(2):236-40.

de Jonghe B, Sharshar T, Lefaucheur JP, et al, "Paresis Acquired in the Intensive Care Unit. A Prospective Multicenter Study,"JAMA, 2002, 288(22):2859-67.

Gamsu HR, Mullinger BM, Donnai P, et al, "Antenatal Administration of Betamethasone to Prevent Respiratory Distress Syndrome in Preterm Infants: Report of a UK Multicentre Trial,"Br J Obstet Gynaecol, 1989, 96(4):401-10.

Hotchkiss RS and Karl IE, "The Pathophysiology and Treatment of Sepsis,"N Engl J Med, 2003, 348(2):138-50.

Liggins GC and Howie RN, "A Controlled Trial of Antepartum Glucocorticoid Treatment of Respiratory Distress Syndrome in Premature Infants,"Pediatrics, 1972, 50:515-25.

Salem M, Tainsh RE Jr, Bromberg J, et al, "Perioperative Glucocorticoid Coverage. A Reassessment 42 Years After Emergence of a Problem,"Ann Surg, 1994, 219(4):416-25.

"Technical Report: Congenital Adrenal Hyperplasia," American Academy of Pediatrics, Section on Endocrinology and Committee on Genetics, Pediatrics, 2000, 106(6):1511-8.