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Hydrocortisone (Systemic)

Pronunciation

Pronunciation

(hye droe KOR ti sone)

Index Terms

  • A-hydroCort
  • Compound F
  • Cortisol
  • Hydrocortisone Sodium Succinate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Injection, as sodium succinate [strength expressed as base]:

A-Hydrocort: 100 mg (1 ea [DSC])

Solu-CORTEF: 100 mg (1 ea)

Solution Reconstituted, Injection, as sodium succinate [strength expressed as base, preservative free]:

Solu-CORTEF: 100 mg (1 ea); 250 mg (1 ea); 500 mg (1 ea); 1000 mg (1 ea)

Tablet, Oral, as base:

Cortef: 5 mg, 10 mg, 20 mg [scored]

Generic: 5 mg, 10 mg, 20 mg

Brand Names: U.S.

  • A-Hydrocort [DSC]
  • Cortef
  • Solu-CORTEF

Pharmacologic Category

  • Corticosteroid, Systemic

Pharmacology

Short-acting corticosteroid with minimal sodium-retaining potential; decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability

Absorption

Rapid

Distribution

Vd: IV: 27 ± 7 L (Czock 2005)

Metabolism

Hepatic

Excretion

Urine (Czock 2005)

Onset of Action

IV: 1 hour

Time to Peak

Plasma: Oral: 1.2 ± 0.4 hours (Czock 2005)

Half-Life Elimination

IV: 2 ± 0.3 hours; Oral: 1.8 ± 0.5 hours (Czock 2005)

Protein Binding

IV: 92% ± 2% (Czock 2005)

Use: Labeled Indications

Allergic states: Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in drug hypersensitivity reactions, perennial or seasonal allergic rhinitis, serum sickness, transfusion reactions, or acute noninfectious laryngeal edema (epinephrine is the drug of first choice).

Dermatologic diseases: Atopic dermatitis; bullous dermatitis herpetiformis; contact dermatitis; exfoliative dermatitis; exfoliative erythroderma; pemphigus; severe erythema multiforme (Stevens-Johnson syndrome); severe psoriasis; severe seborrheic dermatitis; mycosis fungoides.

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.

Endocrine disorders: Acute adrenocortical insufficiency; congenital adrenal hyperplasia; hypercalcemia associated with cancer; nonsuppurative thyroiditis; primary or secondary adrenocortical insufficiency; preoperatively and in the event of serious trauma or illness, in patients with known adrenal insufficiency or when adrenocortical reserve is doubtful; shock unresponsive to conventional therapy if adrenocortical insufficiency exists or is suspected.

GI diseases: To tide the patient over a critical period of the disease in ulcerative colitis and regional enteritis.

Hematologic disorders: Acquired (autoimmune) hemolytic anemia; congenital (erythroid) hypoplastic anemia (Diamond Blackfan anemia); erythroblastopenia (RBC anemia); idiopathic thrombocytopenic purpura in adults; pure red cell aplasia; select cases of secondary thrombocytopenia.

Neoplastic diseases: Palliative management of leukemias and lymphomas (adults); acute leukemia of childhood.

Nervous system: Acute exacerbations of multiple sclerosis; cerebral edema associated with primary or metastatic brain tumor, or craniotomy. Note: Treatment guidelines recommend the use of high-dose IV or oral methylprednisolone for acute exacerbations of multiple sclerosis (AAN [Scott 2011]; NICE 2014).

Ophthalmic diseases: Severe acute and chronic allergic and inflammatory processes involving the eye, such as allergic conjunctivitis; allergic corneal marginal ulcers; anterior segment inflammation; chorioretinitis; diffuse posterior uveitis and choroiditis; herpes zoster ophthalmicus; iritis and iridocyclitis; keratitis; optic neuritis; sympathetic ophthalmia; other ocular inflammatory conditions unresponsive to topical corticosteroids.

Respiratory diseases: Aspiration pneumonitis; bronchial asthma; berylliosis; fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy; idiopathic eosinophilic pneumonias; Loeffler syndrome (not manageable by other means); symptomatic sarcoidosis.

Rheumatic disorders: As adjunctive therapy for short-term administration in acute and subacute bursitis, acute gouty arthritis, acute nonspecific tenosynovitis, ankylosing spondylitis, epicondylitis, posttraumatic osteoarthritis, psoriatic arthritis, rheumatoid arthritis, including juvenile rheumatoid arthritis, synovitis of osteoarthritis; during an exacerbation or as maintenance therapy in acute rheumatic carditis, dermatomyositis (polymyositis), temporal arteritis, and systemic lupus erythematosus.

Miscellaneous: Trichinosis with neurologic or myocardial involvement; tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy.

Use: Unlabeled

Management of septic shock when blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy; treatment of thyroid storm

Contraindications

Hypersensitivity to hydrocortisone or any component of the formulation; systemic fungal infections; use in premature infants (formulations containing benzyl alcohol only); idiopathic thrombocytopenia purpura (IM administration only); intrathecal administration; live or live, attenuated virus vaccines (with immunosuppressive doses of corticosteroids).

Documentation of allergenic cross-reactivity for corticosteroids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Adjust dose depending upon condition being treated and response of patient. The lowest possible dose should be used to control the condition; when dose reduction is possible, the dose should be reduced gradually. In life-threatening situations, parenteral doses larger than the oral dose may be needed.

Anti-inflammatory or immunosuppressive:

IM, IV: Initial: 100 to 500 mg/dose at intervals of 2, 4, or 6 hours.

Oral: Initial: 20 to 240 mg/day.

Multiple sclerosis, acute exacerbations:

Note: Treatment guidelines recommend the use of high-dose IV or oral methylprednisolone for acute exacerbations of multiple sclerosis (AAN [Scott 2011]; NICE 2014).

IM, IV: 800 mg/day for 1 week, followed by 320 mg every other day for 1 month.

Oral: 200 mg/day for 1 week, followed by 80 mg every other day for 1 month.

Adrenal insufficiency:

Acute adrenal insufficiency (adrenal crisis) (off-label dose):100 mg IV bolus, immediately followed by 200 mg over 24 hours as a continuous IV infusion or in divided doses (IM or IV) every 6 hours, then 100 mg over 24 hours the following day (Allolio 2015; ES [Bornstein 2016]). Alternatively, may administer 100 mg IV bolus, then 50 to 75 mg IV every 6 hours for 24 hours, followed by a slow taper over the next 72 hours (administering doses every 4 to 6 hours during taper) (Gardner 2011). Note: Appropriate fluid resuscitation is also required (ES [Bornstein 2016]; Gardner 2011).

Chronic primary adrenal insufficiency (physiologic replacement) (off-label dose): Oral: 15 to 25 mg daily in 2 to 3 divided doses. Administer the largest dose in the morning upon awakening, followed by next dose 2 hours after lunch (two-dose regimen) or next dose at lunch, followed by smallest dose in the afternoon no later than 4 to 6 hours before bedtime (three-dose regimen) (ES [Bornstein 2016]).

Temporary adrenal insufficiency (temporary), physiologic replacement following resection of an ACTH-producing tumor or unilateral adrenalectomy (off-label dose): Oral: 10 to 12 mg/m2/day in 2 to 3 divided doses, with the first dose taken as soon as possible after waking; continue hydrocortisone until HPA axis recovers, generally 6 to 12 months following resection of ACTH-producing tumors or 18 months following unilateral adrenalectomy (ES [Neiman 2015]).

Congenital adrenal hyperplasia (off-label dose): Oral: 15 to 25 mg/day in 2 to 3 divided doses (Speiser 2010).

Stress dosing in patients known to be adrenally-suppressed (ie, prevention of adrenal crisis in glucocorticoid-treated patients) (off-label dose):

Sickness:

Illness with fever: Oral: Double the routine oral hydrocortisone dose until recovery for fever >38°C [100.4°F] or triple the routine oral hydrocortisone dose until recovery for fever >39°C [102.2°F]); return to standard dose within 1 to 2 days (Allolio 2015)

Gastroenteritis with vomiting and/or diarrhea: IM, SubQ: 100 mg dose given early in course of illness; repeat after 6 to 12 hours (Allolio 2015)

Severe infection (eg, pneumonia/with altered cognition): IM, SubQ: 100 mg dose given early in course of illness; repeat after 6 to 12 hours until recovery (Allolio 2015)

Surgery:

Minor stress (ie, inguinal herniorrhaphy): IV: 25 mg/day for 1 day (Coursin 2002; Salem 1994)

Moderate stress (ie, joint replacement, cholecystectomy): IV: 50 to 75 mg/day (25 mg every 8 to 12 hours) for 1 to 2 days (Coursin 2002; Salem 1994)

Major stress (pancreatoduodenectomy, esophagogastrectomy, cardiac surgery): IV: 100 to 150 mg/day (50 mg every 8 to 12 hours) for 2 to 3 days (Coursin 2002; Salem 1994)

Septic shock (off-label use): IV: 50 mg every 6 hours (Annane 2002; COIITSS Study Investigators 2010). Practice guidelines suggest administering 200 mg daily as a continuous infusion over 24 hours to prevent adverse effects (eg, hyperglycemia) (Dellinger 2013; Weber-Carstens 2007); however, the impact of continuous infusion on patient outcomes has not been formally evaluated. Taper slowly (over several days) when vasopressors are no longer required; do not stop abruptly. Note: Hydrocortisone should be used alone (ie, without fludrocortisone) (Dellinger 2013).

Thyroid storm (off-label use): IV: 300 mg loading dose, followed by 100 mg every 8 hours (Bahn 2011)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Adjust dose depending upon condition being treated and response of patient. The lowest possible dose should be used to control the condition; when dose reduction is possible, the dose should be reduced gradually. In life-threatening situations, parenteral doses larger than the oral dose may be needed.

Anti-inflammatory or immunosuppressive:

Infants and Children:

Oral: 2.5 to 10 mg/kg/day or 75 to 300 mg/m2/day in divided doses every 6 to 8 hours (Kliegman 2007).

IM, IV:

Manufacturer labeling: Initial: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day in 3 or 4 divided doses.

Alternate dosing: 1 to 5 mg/kg/day or 30 to 150 mg/m2/day divided every 12 to 24 hours (Kliegman 2007).

Adolescents: Oral, IM, IV, SubQ: 15 to 240 mg every 12 hours (Kliegman 2007).

Congenital adrenal hyperplasia (off-label dose): Oral: (tablets): Infants, Children, and Adolescents: Note: Administer morning dose as early as possible. Tablets may result in more reliable serum concentrations than oral liquid formulation; use of oral suspension is not recommended. Doses must be individualized by monitoring growth, bone age, and hormonal levels; mineralocorticoid (eg, fludrocortisone) and sodium supplement may be required in salt losers (AAP 2000; AAP 2010; Endocrine Society 2010).

Initial: 10 to 15 mg/m2/day in 3 divided doses; higher initial doses (20 mg/m2/day) may be required to achieve initial target hormone serum concentrations (AAP 2010; Endocrine Society 2010).

Maintenance dose: Usual requirement:

Infants: 2.5 to 5 mg/dose 3 times daily.

Children: 5 to 10 mg/dose 3 times daily.

Adolescents: Refer to adult dosing.

Physiologic replacement (off-label dose): Infants and Children: Oral: 8 to 10 mg/m2/day divided every 8 hours; up to 12 mg/m2/day in some patients; to replicate diurnal variation, the highest doses are typically administered in the morning and mid-day dose with the lower dose in the evening (Ahmet 2011; Elder 2015; Gupta 2008; Maguire 2007; Shulman 2007).

Septic shock (off-label use): Infants, Children, and Adolescents: IV: 50 to 100 mg/m2/day (Dellinger 2013; Marx 2014; Shulman 2007); in some cases, doses may be titrated up to 50 mg/kg/day for shock reversal; however, efficacy data variable with the higher doses (Brierley 2009; Menon 2012). Note: Use recommended only in fluid refractory, catecholamine-resistant shock, and suspected or proven absolute (classic) adrenal insufficiency.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Reconstitution

IV bolus or IM administration: Reconstitute 100 mg vials with bacteriostatic water or bacteriostatic sodium chloride (not >2 mL).

IV infusion administration: Add reconstituted solutions to an appropriate volume of D5W, NS, or D5NS (100 to 1,000 mL for a 100 mg solution; 250 to 1,000 mL for a 250 mg solution; 500 to 1,000 mL for a 500 mg solution; 1,000 mL for a 1,000 mg solution). In cases where administration of a small volume of fluid is desirable, 100 to 3,000 mg of hydrocortisone may be added to 50 mL of D5W or NS.

Act-O-Vial: Press 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.

Extemporaneously Prepared

A 2.5 mg/mL oral suspension may be made with either tablets or powder and a vehicle containing sodium carboxymethylcellulose (1 g), syrup BP (10 mL), hydroxybenzoate 0.1% preservatives (0.1 g), polysorbate 80 (0.5 mL), citric acid (0.6 g), and water. To make the vehicle, dissolve the hydroxybenzoate, citric acid, and syrup BP in hot water. Cool solution and add the carboxymethylcellulose; leave overnight. Crush twelve-and-one-half 20 mg hydrocortisone tablets (or use 250 mg of powder) in a mortar and reduce to a fine powder while adding polysorbate 80. Add small portions of vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 100 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add sufficient quantity of vehicle to make 100 mL. Label “shake well” and “refrigerate”. Stable for 90 days.

Fawcett JP, Boulton DW, Jiang R, et al, "Stability of Hydrocortisone Oral Suspensions Prepared From Tablets and Powder," Ann Pharmacother, 1995, 29(10):987-90.8845559

Administration

Oral: Administer with food or milk to decrease GI upset.

Parenteral: For IM or IV administration: Dermal and/or subdermal skin depression may occur at injection site.

IM: Avoid injection into deltoid muscle (high incidence of subcutaneous atrophy).

IV bolus: Administer undiluted over at least 30 seconds; for large doses (≥500 mg), administer over 10 minutes.

IV intermittent infusion: Further dilute in a compatible fluid and administer over 20 to 30 minutes.

Dietary Considerations

Systemic use of corticosteroids may require a diet with increased potassium, vitamins A, B6, C, D, folate, calcium, zinc, phosphorus, and decreased sodium. Some products may contain sodium.

Compatibility

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: Incompatible with ciprofloxacin, diazepam, idarubicin, midazolam, phenytoin, sargramostim.

Compatibility in syringe: Incompatible with doxapram, oxytocin, pantoprazole.

Storage

Oral: Store at 20°C to 25°C (68°F to 77°F).

Injection: Store intact vials at 20°C to 25°C (68°F to 77°F); protect from light. Heat sensitive; do not autoclave vial. Reconstituted solutions are stable for 3 days at 20°C to 25°C (68°F to 77°F); protect from light. Solutions prepared for IV infusion are stable for at least 4 hours.

Drug Interactions

Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Monitor therapy

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid combination

Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B. Monitor therapy

Androgens: Corticosteroids (Systemic) may enhance the fluid-retaining effect of Androgens. Monitor therapy

Antacids: May decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects. Consider therapy modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Aprepitant: May increase the serum concentration of Corticosteroids (Systemic). Management: No dose adjustment is needed for single 40 mg aprepitant doses. For other regimens, reduce oral dexamethasone or methylprednisolone doses by 50%, and IV methylprednisolone doses by 25%. Antiemetic regimens containing dexamethasone reflect this adjustment. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Monitor therapy

Calcitriol (Systemic): Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol (Systemic). Monitor therapy

Ceritinib: Corticosteroids may enhance the hyperglycemic effect of Ceritinib. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Hydrocortisone (Systemic). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Deferasirox: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Desirudin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Desirudin. More specifically, corticosteroids may increase hemorrhagic risk during desirudin treatment. Management: Discontinue treatment with systemic corticosteroids prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification

DilTIAZem: May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Estrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Consider therapy modification

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Indacaterol: May enhance the hypokalemic effect of Corticosteroids (Systemic). Monitor therapy

Indium 111 Capromab Pendetide: Corticosteroids (Systemic) may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination

Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

MiFEPRIStone: May diminish the therapeutic effect of Corticosteroids (Systemic). MiFEPRIStone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (e.g., for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Avoid combination

Mitotane: May decrease the serum concentration of Corticosteroids (Systemic). Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Consider therapy modification

Nicorandil: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nicorandil. Gastrointestinal perforation has been reported in association with this combination. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

NSAID (COX-2 Inhibitor): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). Monitor therapy

NSAID (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (Nonselective). Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Quinolone Antibiotics: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Quinolone Antibiotics. Specifically, the risk of tendonitis and tendon rupture may be increased. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Salicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Telaprevir: Corticosteroids (Systemic) may decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Corticosteroids (Systemic). Management: Concurrent use of telaprevir and systemic corticosteroids is not recommended. When possible, consider alternatives. If used together, employ extra caution and monitor closely for excessive corticosteroid effects and diminished telaprevir effects. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Urea Cycle Disorder Agents: Corticosteroids (Systemic) may diminish the therapeutic effect of Urea Cycle Disorder Agents. More specifically, Corticosteroids (Systemic) may increase protein catabolism and plasma ammonia concentrations, thereby increasing the doses of Urea Cycle Disorder Agents needed to maintain these concentrations in the target range. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification

Warfarin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Warfarin. Monitor therapy

Test Interactions

May decrease response to skin tests

Adverse Reactions

Frequency not defined.

Cardiovascular: Atheromatous embolism, bradycardia, cardiac arrhythmia, cardiac failure, cardiomegaly, circulatory shock, edema, hypertension, hypertrophic cardiomyopathy (premature infants), myocardial rupture (post-myocardial infarction), syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis

Central nervous system: Delirium, depression, emotional lability, euphoria, hallucination, headache, increased intracranial pressure, insomnia, malaise, myasthenia, nervousness, neuritis, neuropathy, personality changes, pseudotumor cerebri, psychic disorder, psychosis, seizure, tingling of skin, vertigo

Dermatologic: Acne vulgaris, allergic dermatitis, alopecia, atrophic striae, burning sensation of skin, diaphoresis, erythema, exfoliation of skin, hyperpigmentation, hypopigmentation, skin atrophy, skin rash, sterile abscess, suppression of skin test reaction, urticaria, xeroderma

Endocrine & metabolic: Abnormalities in sperm motility (decreased/increased motility), adrenal suppression, alkalosis, amenorrhea, Cushing's syndrome, diabetes mellitus, fluid retention, growth suppression, hirsutism, HPA-axis suppression, hyperglycemia, hyperlipidemia, hypokalemia, hypokalemic alkalosis, impaired glucose tolerance, menstrual disease, negative nitrogen balance, protein catabolism, sodium retention, spermatozoa disorder (spermatogenesis decreased/increased), weight gain

Gastrointestinal: Abdominal distention, carbohydrate intolerance, dyspepsia, gastrointestinal perforation, hiccups, increased appetite, intestinal disease (intrathecal administration), nausea, pancreatitis, peptic ulcer, ulcerative esophagitis, vomiting

Genitourinary: Bladder dysfunction (intrathecal administration)

Hematologic & oncologic: Bruise, leukocytosis (transient), metastases, petechia

Hepatic: Hepatomegaly, increased serum transaminases

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Infection: Infection

Local: Atrophy at injection site, post-injection flare (intra-articular use), skin edema

Neuromuscular & skeletal: Abnormal fat deposits, amyotrophy, arthralgia, bone fracture, Charcot-like arthropathy, myopathy, osteonecrosis (femoral and humoral heads), osteoporosis, rupture of tendon, vertebral compression fracture

Ophthalmic: Cataract, exophthalmos, glaucoma, increased intraocular pressure

Miscellaneous: Tissue necrosis (avascular), wound healing impairment

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercorticism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections.

• Anaphylactoid reactions: Rare cases of anaphylactoid reactions have been observed in patients receiving corticosteroids.

• Dermal changes: Avoid injection or leakage into the dermis; dermal and/or subdermal skin depression may occur at the site of injection. Avoid deltoid muscle injection; subcutaneous atrophy may occur.

• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to killed or inactivated vaccines. Exposure to chickenpox or measles should be avoided. Corticosteroids should not be used for cerebral malaria, fungal infections, or viral hepatitis. Close observation is required in patients with latent tuberculosis and/or TB reactivity; restrict use in active TB (only fulminating or disseminated TB in conjunction with antituberculosis treatment). Latent or active amebiasis should be ruled out in any patient with recent travel to tropical climates or unexplained diarrhea prior to corticosteroid initiation. Use with extreme caution in patients with Strongyloides infections; hyperinfection, dissemination and fatalities have occurred.

• Kaposi sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); if noted, discontinuation of therapy should be considered (Goedert 2002).

• Myopathy: Acute myopathy has been reported with high dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor creatine kinase; recovery may be delayed.

• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including euphoria, insomnia, mood swings, personality changes, severe depression, or psychotic manifestations. Pre-existing psychiatric conditions may be exacerbated by corticosteroid use.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with HF and/or hypertension; use has been associated with fluid retention, electrolyte disturbances, and hypertension. Use with caution following acute MI; corticosteroids have been associated with myocardial rupture.

• Diabetes: Use corticosteroids with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.

• Gastrointestinal disease: Use with caution in patients with GI diseases (diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, ulcerative colitis, abscess or other pyogenic infection) due to perforation risk.

• Head injury: Increased mortality was observed in patients receiving high-dose IV methylprednisolone; high-dose corticosteroids should not be used for the management of head injury.

• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred especially during initial treatment with corticosteroids.

• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Oral steroid treatment is not recommended for the treatment of acute optic neuritis; may increase frequency of new episodes and does not affect short- or long-term visual outcomes. Use with caution in patients with ocular herpes simplex; corneal perforation may occur; do not use in active ocular herpes simplex. Consider routine eye exams in chronic users.

• Osteoporosis: Use with caution in patients with osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures.

• Pheochromocytoma: Pheochromocytoma crisis has been reported with corticosteroids (may be fatal). Consider the risk of pheochromocytoma crisis prior to administering corticosteroids in patients with suspected pheochromocytoma.

• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.

• Seizure disorders: Use corticosteroids with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.

• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly with the smallest possible effective dose for the shortest duration.

• Pediatric: May affect growth velocity; growth should be routinely monitored in pediatric patients.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Diluent for injection may contain benzyl alcohol and some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.

• Epidural injection: Corticosteroids are not approved for epidural injection. Serious neurologic events (eg, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke), some resulting in death, have been reported with epidural injection of corticosteroids, with and without use of fluoroscopy.

• Stress: Patients may require higher doses when subject to stress (ie, trauma, surgery, severe infection).

Monitoring Parameters

Serum glucose, electrolytes; blood pressure, weight, presence of infection; monitor IOP with therapy >6 weeks; bone mineral density; assess HPA axis suppression (eg, ACTH stimulation test, morning plasma cortisol test, urinary free cortisol test); growth in pediatric patients.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed with corticosteroids in animal reproduction studies. Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts (Park-Wyllie 2000; Pradat 2003). Systemic corticosteroids may also influence fetal growth (decreased birth weight); however, information is conflicting (Lunghi 2010). Hypoadrenalism may occur in newborns following maternal use of corticosteroids in pregnancy (monitor). In general, when systemic corticosteroids are needed in pregnancy, it is recommended to use the lowest effective dose for the shortest duration of time, avoiding high doses during the first trimester (Leachman 2006; Lunghi 2010; Makol 2011; Østensen 2009). When treating women with Primary Adrenal Insufficiency (PAI) during pregnancy, hydrocortisone is the preferred corticosteroid. Doses may need adjusted as pregnancy progresses and stress doses may be required during active labor. Pregnant women with PAI should be monitored at least once each trimester (Bornstein 2016).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, insomnia, or agitation. Have patient report immediately to prescriber signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss); signs of infection; signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit); signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat); signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting); signs of Cushing’s disease (weight gain in upper back or abdomen; moon face; severe headache; or slow healing); severe loss of strength and energy; irritability; tremors; tachycardia; confusion; dizziness; sweating a lot; shortness of breath; excessive weight gain; swelling of arms or legs; signs of skin changes (acne, stretch marks, slow healing, or hair growth); moon face; buffalo hump; severe headache; passing out; muscle weakness; bone pain; joint pain; menstrual changes; angina; vision changes; eye pain; severe eye irritation; mood changes; behavioral changes; depression; seizures; bruising; bleeding; severe abdominal pain; black, tarry, or bloody stools; or vomiting blood (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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