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.
Adrenal insufficiency, adrenal crisis, treatment and prevention:
Treatment:
Note: Appropriate fluid resuscitation is also required (ES [Bornstein 2016]; Gardner 2011).
IV: 100 mg IV bolus given immediately, followed by 25 to 75 mg IV every 6 hours or 200 mg/24 hours as a continuous IV infusion for the first 24 hours. Reassess patient after the initial 24 hours; if clinical status has improved may begin gradually tapering the dose. Once patient is stable, may resume chronic maintenance oral dosing (Allolio 2015; ES [Bornstein 2016]; ES [Speiser 2018]; Gardner 2011).
Prevention (ie, stress dosing):
Note: For use in patients with known adrenal insufficiency or suspected adrenal insufficiency (eg, Cushingoid appearance, prolonged glucocorticoid therapy ≥5 mg/day of prednisone or equivalent) to prevent development of adrenal crisis (LaRochelle 1993; Salem 1994).
Acute physiologic stress/illness:
Febrile illness: Oral: Double the chronic maintenance dose for fever 38°C (100.4°F) to 39°C (102.2°F) or triple the chronic maintenance oral dose for fever >39°C (102.2°F), then return to baseline dose within 1 to 3 days following recovery of fever (Allolio 2015; ES [Bornstein 2016]).
Patients unable to tolerate oral medication (eg, due to vomiting or diarrhea): IM, SubQ: 100 mg dose given early in course of illness; repeat after 6 to 12 hours (Allolio 2015; ES [Bornstein 2016]).
Labor/Delivery: IM, IV: Dosing is individualized (Bothou 2020). One example regimen includes 100 mg IV loading dose at the onset of active labor (or immediately before anesthesia in patients undergoing caesarean section), followed by 50 to 100 mg every 6 hours (given as IM or IV injections) or 200 mg/day given as a continuous IV infusion until delivery; taper dose over 1 to 2 days after delivery before resuming baseline dose (ES [Bornstein 2016]; ADSHG 2017). Usual dosing range: 50 to 100 mg every 6 to 8 hours or 200 to 300 mg/24 hours (Lebbe 2013).
Surgical stress:
Minor surgical stress (eg, hernia repair, procedures with local anesthetic): IV, Oral: Continue chronic maintenance dose administered orally or IV (no additional supplementation needed) (Coursin 2002; Hamrahian 2020; Salem 1994); may give an additional oral dose (eg, 20 mg) postoperatively if signs or symptoms of adrenal insufficiency are present (Allolio 2015; Husebye 2014).
Moderate surgical stress (eg, 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 surgical stress (eg, major bowel surgery, cardiothoracic surgery, cesarean delivery): IV, IM:
100 to 150 mg/day (50 mg every 8 to 12 hours) (Coursin 2002; Salem 1994).
or
100 mg IV loading dose immediately before anesthesia, followed by 50 to 100 mg every 6 hours (given as IM or IV injection) or 200 mg/day given as a continuous IV infusion (ADSHG 2017; ES [Bornstein 2016]).
Note: Taper dose and resume oral regimen as clinical status improves (eg, after 1 to 3 days) (Coursin 2002; ES [Bornstein 2016]; Salem 1994).
Adrenal insufficiency, chronic (eg, primary, secondary, classic congenital adrenal hyperplasia) : Oral: 15 to 25 mg/day in 2 to 3 divided doses. Administer the largest dose in the morning upon awakening, followed by next dose 2 hours after lunch (2-dose regimen) or next dose at lunch, followed by smallest dose in the afternoon no later than 4 to 6 hours before bedtime (3-dose regimen) (ES [Bornstein 2016]; ES [Fleseriu 2016]; ES [Speiser 2018]).
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]).
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.
Asthma, acute exacerbation (off-label dose): Oral: 200 mg in divided doses for 5 to 7 days (GINA 2020).
COVID-19, hospitalized patients (severe or critical) (alternative agent) (off-label use):
Note: Hydrocortisone is recommended for treatment of COVID-19 in hospitalized patients requiring supplemental oxygen or ventilatory support when dexamethasone is not available. Corticosteroid dosing is taken from a study that used dexamethasone; the equivalent dose of hydrocortisone (or other glucocorticoid) may be substituted when dexamethasone is unavailable (NIH 2021; WHO 2020).
IV, Oral: 50 mg every 8 hours for up to 10 days (or until discharge if sooner) (NIH 2021; WHO 2020). For additional information, including use of concomitant therapies, refer to the COVID-19 dosing section of the Dexamethasone monograph.
Iodinated contrast media allergic-like reaction, prevention: Note: Generally reserved for patients with a prior allergic-like or unknown-type iodinated contrast reaction who will be receiving another iodinated contrast agent. Nonurgent premedication with an oral corticosteroid is generally preferred when contrast administration is scheduled to begin in ≥12 hours; however, IV hydrocortisone may be considered in patients unable to take oral medications. Consider an urgent (accelerated) regimen with an IV corticosteroid for patients requiring contrast in <12 hours (ACR 2021).
Nonurgent regimen (alternative agent): IV: 200 mg administered 13 hours, 7 hours, and 1 hour before contrast medium administration in combination with oral or IV diphenhydramine (ACR 2021).
Urgent (accelerated) regimen: IV: 200 mg immediately, then 200 mg every 4 hours until contrast medium administration in combination with oral or IV diphenhydramine. In emergent situations (ie, <4 to 5 hours until contrast is required), may consider hydrocortisone 200 mg in combination with IV diphenhydramine 1 hour prior to contrast (ACR 2021).
Septic shock (off-label use): Note: Corticosteroids should only be used for septic shock that is not responsive to volume resuscitation and vasopressors (Rhodes 2017; SCCM/ESICM [Annane 2017]).
IV: 50 mg bolus every 6 hours, either as monotherapy (Sprung 2008) or in combination with fludrocortisone (Annane 2002; Annane 2018) or 200 mg/day as a continuous infusion (Venkatesh 2018). Guidelines suggest a therapy duration of ≥3 days (Rhodes 2017; SCCM/ESICM [Annane 2017]); most studies treated for up to 7 days; not all studies tapered therapy. May consider a slow taper over several days when vasopressors are no longer required to avoid possible hemodynamic deterioration which may occur with abrupt withdrawal (Keh 2003; Rhodes 2017).
Note: In patients with septic shock, low-dose hydrocortisone may cause a significant increase in hyperglycemia and hypernatremia. A small study demonstrated that repetitive bolus doses of hydrocortisone caused significant hyperglycemia that was not seen during continuous infusion (Weber-Carstens 2007); practice guidelines recommend strategies for avoidance and/or detection of these side effects, such as dosing by continuous infusion (Rhodes 2017).
Thyroid storm (off-label use): IV: 300 mg loading dose, followed by 100 mg every 8 hours (ATA [Ross 2016]).
Ulcerative colitis, acute (severe), remission induction (off- label dose): IV: 100 mg every 6 to 8 hours (ACG [Rubin 2019]). Some experts recommend not exceeding 300 mg/day to decrease the risk of colectomy (AGA [Feuerstein 2020]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
(For additional information see "Hydrocortisone (systemic): Pediatric drug information")
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.
Adrenal insufficiency; acute (adrenal crisis): Dosage regimens variable; some experts recommend using weight-directed dosing for first dose (AAP [Shenoi 2020]):
Weight-directed: Limited data available: Infants, Children, and Adolescents: IM, IV (preferred), Intraosseous: Initial: 2 to 3 mg/kg once; maximum dose: 100 mg/dose; then for infants: 1 to 5 mg/kg/dose every 6 hours; for children and adolescents, see BSA- or age-directed dosing (AAP [Hegenbarth 2008]; AAP [Shenoi 2020]; Cameron 2012; Marx 2014).
BSA-directed dosing: Limited data available: Infants, Children, and Adolescents: IM, IV (preferred), Intraosseous: Initial: 50 to 100 mg/m2 once followed by 50 to 100 mg/m2/day in 4 divided doses (Ahmet 2011; Auron 2015; AAP [Hegenbarth 2008]; Shulman 2007).
Age-directed dosing (fixed dosing): Limited data available (AAP [Shenoi 2020]; Cameron 2012; Elder 2015; Kliegman 2020):
Infants: IM, IV (preferred), Intraosseous: 10 to 25 mg once followed by 10 to 25 mg/day in divided doses every 6 hours for 24 hours then subsequent dose reductions and rate determined by patient response.
Children <5 years (eg, young children): IM, IV (preferred), Intraosseous: 25 to 50 mg once followed by 25 to 50 mg/day in divided doses every 6 hours for 24 hours then subsequent dose reductions and rate determined by patient response.
Children ≥5 years (eg, older children): IM, IV (preferred), Intraosseous: 50 to 100 mg once followed by 50 mg/day in divided doses every 6 hours for 24 hours then subsequent dose reductions and rate determined by patient response.
Adolescents: IM, IV (preferred), Intraosseous: 100 mg once followed by 100 mg/day in divided doses every 6 hours for 24 hours then subsequent dose reduction and rate determined by patient response.
Anti-inflammatory or immunosuppressive: Note: Dosing range variable; individualize dose for disease state and patient response.
Infants and Children:
Oral: 2.5 to 10 mg/kg/day or 75 to 300 mg/m2/day divided every 6 to 8 hours (Gal 2007).
IM, IV:
Manufacturer's labeling: Initial: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day in 3 or 4 divided doses.
Alternate dosing: Limited data available: 1 to 5 mg/kg/day or 30 to 150 mg/m2/day divided every 12 to 24 hours (Gal 2007).
Adolescents: Oral, IM, IV, SubQ: 15 to 240 mg every 12 hours (Gal 2007).
Congenital adrenal hyperplasia (CAH); chronic:
Note: Administer morning dose as early as possible. Tablets and oral sprinkles (Alkindi) may result in more reliable serum concentrations than oral suspension formulation; use of oral suspension is not recommended in growing individuals. Individualize dose by monitoring growth, hormone levels, and bone age; mineralocorticoid (eg, fludrocortisone) and sodium supplement may be required in salt losers (AAP 2000; AAP 2010; Endocrine Society [Speiser 2018]). When using the oral sprinkles, round dose to nearest 0.5 or 1 mg; when using regular oral tablets, the smallest available dose is 2.5 mg (1/2 of 5 mg tablet). When converting dosage forms between regular tablets and oral sprinkles, the same daily dose may be used. See "Stress dosing; supplemental" for management of patients with CAH during times of physiological stress.
Infants, Children, and Adolescents:
BSA-directed dosing: Oral (tablets, sprinkles): Initial: 8 to 15 mg/m2/day in 3 divided doses; usual range: 10 to 15 mg/m2/day; higher initial doses (20 mg/m2/day) may be required to achieve initial target hormone serum concentrations; older patients may be able to transition to twice-daily dosing (AAP 2010; Elder 2015; Endocrine Society [Speiser 2018]; manufacturer's labeling).
Fixed dosing (AAP 2000): Oral (tablets): Usual requirement:
Infants: 2.5 to 5 mg/dose 3 times/day.
Children: 5 to 10 mg/dose 3 times/day.
Adolescents (fully grown): 15 to 25 mg/day divided in 2 to 3 daily doses.
Physiologic replacement: 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 midday dose with the lower dose in the evening (Ahmet 2011; Elder 2015; Gupta 2008; Maguire 2007; Shulman 2007).
Stress dosing; supplemental: Limited data available; dosage regimens variable:
Note: Dosing based on the level of physiological stress related to condition; dose should be individualized based on patient and continued until resolution of stressful condition (usually 24 to 48 hours). Typically, supplementation for emotional or minimal physiological stress conditions or prior to exercise is not necessary. Dosing is generally 2 to 3 times physiologic replacement level (Elder 2015; Endocrine Society [Speiser 2018]; Shulman 2007).
Infants, Children, and Adolescents:
BSA-directed dosing (Ahmet 2011; Shulman 2007): Oral, IM, IV:
Mild to moderate stress: 20 to 50 mg/m2/day divided into 3 or 4 doses; doses on the lower end of the range (20 to 30 mg/m2/day) may be divided twice daily.
Major stress or surgery: 100 mg/m2/day in divided doses every 6 hours.
Planned surgery: Pre-anesthesia of 50 mg/m2 IV or IM administered 30 to 60 minutes prior to surgery followed by second dose of 50 mg/m2 as a continuous IV infusion or in divided doses every 6 hours for at least 24 hours.
Age-directed for moderate stress in patients with congenital adrenal hyperplasia (Endocrine Society [Speiser 2018]):
Infants and preschool children: IV: Initial dose: 25 mg once, followed by a daily dose that is 3 to 4 times the patient's standard maintenance dose in divided doses every 6 hours.
School-age children: IV: Initial dose: 50 mg once, followed by a daily dose that is 3 to 4 times the patient's standard maintenance dose in divided doses every 6 hours.
Adolescents: IV: Initial dose: 100 mg once, followed by a daily dose that is 3 to 4 times the patient's standard maintenance dose in divided doses every 6 hours.
Septic shock, fluid and catecholamine-refractory with suspected/proven adrenal insufficiency: Limited data available:
BSA-directed dosing : Infants, Children, and Adolescents: IV: 50 to 100 mg/m2/day. Note: The maximum adult daily dose is 200 mg/day (~100 mg/m2/day) (ACCM/SCCM [Davis 2017]; Marx 2014; SCCM [Dellinger 2013]; Shulman 2007). In some cases, doses may be titrated up to 50 mg/kg/day as a continuous IV infusion, if necessary, for shock reversal in the short term; however, efficacy data variable with the higher doses (Brierley 2009; SCCM [Dellinger 2013]).
Weight- directed dosing (AAP [Shenoi 2020]): Note: Use if BSA not available:
Infants, Children, and Adolescents: IV, Intraosseous: 2 mg/kg as a single bolus dose; maximum dose: 100 mg/dose.
Age- directed dosing (AAP [Shenoi 2020]): Note: Use if BSA and weight are not available:
Infants and Children <3 years: IV, Intraosseous: 25 mg as a single bolus dose.
Children ≥3 to <12 years: IV, Intraosseous: 50 mg as single bolus dose.
Children ≥12 years and Adolescents: IV, Intraosseous: 100 mg as a single bolus dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Sprinkle, Oral:
Alkindi Sprinkle: 0.5 mg, 1 mg, 2 mg, 5 mg
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
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Injection:
Generic: 250 mg ([DSC]); 500 mg ([DSC]); 1000 mg ([DSC])
Solution Reconstituted, Injection, as sodium succinate [strength expressed as base]:
Solu-CORTEF: 100 mg (1 ea); 250 mg (1 ea); 500 mg (1 ea); 1000 mg (1 ea)
Generic: 100 mg ([DSC])
Tablet, Oral, as base:
Cortef: 10 mg, 20 mg [contains corn starch]
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Alkindi Sprinkle: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213876s001lbl.pdf#page=14
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.
SubQ (off-label route): Divide injections >1 mL (>50 mg) into 2 or more separate injections (Hahner 2013).
Oral: Administer with food or milk to decrease GI upset; for physiologic replacement in pediatric patients, higher doses are typically administered in the morning and midday with lower doses in the evening to replicate diurnal variation; early evening doses (18:00) may be necessary in some children (doses too close to bedtime can interfere with sleep) (Elder 2015).
Sprinkles (Alkindi): Do not swallow capsule whole. Hold capsule so numeric strength section of the capsule is at the top and tap capsule to ensure all granules in lower section, then open the capsule by squeezing the bottom section and twisting the top off. Granules may be administered by any of the following methods: Pouring granules directly onto patient's tongue; pouring granules onto a spoon and placing in patient's mouth; or sprinkling granules onto a spoon containing a soft food (eg, yogurt, fruit puree) that is cold or at room temperature and then having patient consume preferably within 5 minutes to avoid bitter taste. Avoid getting capsule wet (if capsule is wet, granules may stick and not get delivered in dose). Do not crush or chew granules. Ingest fluids (eg, water, milk, breast milk, infant formula) after dose is administered to ensure all granules swallowed. Do not add granules directly to a liquid; may result in reduced dose delivered as well as a bitter taste. Do not administer through NG or gastric tubes; granules will clog tube.
Parenteral: Hydrocortisone sodium succinate may be administered by IM or IV routes. Dermal and/or subdermal skin depression may occur at the site of injection.
IM: Avoid injection into deltoid muscle (high incidence of SubQ atrophy).
IV bolus: Administer undiluted over at least 30 seconds; for large doses (≥500 mg), administer over 10 minutes.
Intermittent IV infusion: Further dilute in a compatible fluid and administer over 20 to 30 minutes (Miller 1980).
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 (oral only), 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); immune thrombocytopenia (formerly known as 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: Cerebral edema associated with primary or metastatic brain tumor, or craniotomy.
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.
COVID-19, hospitalized patients (severe or critical); In-hospital cardiac arrest; Septic shock; Thyroid storm
Hydrocortisone may be confused with hydrocodone, hydroxychloroquine, hydroCHLOROthiazide
Cortef may be confused with Coreg, Lortab
HCT (occasional abbreviation for hydrocortisone) is an error-prone abbreviation (mistaken as hydroCHLOROthiazide)
Solu-CORTEF may be confused with SOLU-Medrol
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined:
Cardiovascular: Bradycardia, cardiac arrhythmia, cardiac failure (especially in susceptible patients), cardiomegaly, circulatory shock, embolism (fat), hypertension, hypertrophic cardiomyopathy (premature infants), myocardial rupture (post-myocardial infarction), syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis
Dermatologic: Acne vulgaris, allergic dermatitis, atrophic striae, burning sensation of skin (especially in the perineal area after IV injection), diaphoresis, ecchymoses, erythema of skin, facial erythema, hyperpigmentation, hypertrichosis, hypopigmentation, inadvertent suppression of skin test reaction, skin rash, thinning hair, urticaria, xeroderma
Endocrine & metabolic: Adrenocortical insufficiency (secondary unresponsiveness, particularly during trauma, surgery, or illness), Cushing syndrome, decreased serum potassium, drug-induced Cushing’s syndrome, fluid retention, glycosuria, growth retardation, hirsutism, HPA-axis suppression, hyperglycemia (including increased requirements for insulin or oral hypoglycemic agents in diabetes mellitus), hypokalemic alkalosis, impaired glucose tolerance/prediabetes, lipodystrophy, manifestation of prediabetes, menstrual disease, moon face, negative nitrogen balance (due to protein catabolism), pituitary insufficiency (secondary unresponsiveness, particularly during trauma, surgery, or illness), protein catabolism, sodium retention, weight gain
Gastrointestinal: Abdominal distention, gastrointestinal perforation (small and large intestine, particularly in patients with inflammatory bowel disease), hiccups, impaired intestinal carbohydrate absorption, increased appetite, nausea, pancreatitis, peptic ulcer (with possible perforation and hemorrhage), ulcerative esophagitis
Genitourinary: Asthenospermia, oligospermia
Hematologic & oncologic: Leukocytosis, petechia
Hepatic: Hepatomegaly, increased liver enzymes (usually reversible on discontinuation)
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction, nonimmune anaphylaxis
Infection: Increased susceptibility to infection, sterile abscess
Local: Atrophy at injection site (cutaneous and subcutaneous), post-injection flare (intra-articular use), skin edema
Nervous system: Depression, emotional lability, euphoria, headache, increased intracranial pressure (with pseudotumor cerebri; usually following discontinuation), insomnia, malaise, myasthenia, neuritis, neuropathy, paresthesia, personality changes, psychic disorder, seizure, tingling of skin (especially in the perineal area after IV injection), vertigo
Neuromuscular & skeletal: Amyotrophy, aseptic necrosis of femoral head, aseptic necrosis of humeral head, Charcot arthropathy, osteoporosis, pathological fracture (long bones), rupture of tendon (particularly rupture of Achilles tendon), steroid myopathy, vertebral compression fracture
Ophthalmic: Blindness (rare, periocular injection), exophthalmos, glaucoma, increased intraocular pressure, retinopathy (central serous chorioretinopathy), subcapsular posterior cataract
Respiratory: Pulmonary edema
Miscellaneous: Wound healing impairment
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).
Canadian labeling: Additional contraindications (not in US labeling): Herpes simplex of the eye (except for short-term or emergency therapy); vaccinia and varicella (except for short-term or emergency therapy)
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.
Concerns related to adverse effects:
• Adrenal suppression: May cause hypercortisolism 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 (TB) 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. Symptoms usually occur within a few days or weeks of initiation of treatment and usually resolve with dose reduction or discontinuation; monitor for signs and symptoms of behavioral or mood changes. Preexisting 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.
• GI 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; risk may be increased with concurrent use of nonsteroidal anti-inflammatory drugs.
• 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 may cause transient worsening of myasthenia gravis (MG) (eg, within first 2 weeks of treatment); monitor for worsening MG (AAN [Narayanaswami 2021]).
• 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.
• Septic shock or sepsis syndrome: Corticosteroids should not be administered for the treatment of sepsis in the absence of shock (SCCM/ESICM [Annane 2017]).
• Systemic sclerosis: Use with caution in patients with systemic sclerosis; an increase in scleroderma renal crisis incidence has been observed with corticosteroid use. Monitor BP and renal function in patients with systemic sclerosis treated with corticosteroids (EULAR [Kowal-Bielecka 2017]).
• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.
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.
• Capsule: Sprinkles are therapeutically equivalent to tablets; however, compounding tablets into a suspension, or crushing or splitting tablets could lead to a relative difference in exposure on the same nominal dose leading to symptoms of adrenal insufficiency. Dosage adjustments of oral sprinkles may be needed if adrenal insufficiency occurs.
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).
May cause osteoporosis (at any age) or inhibition of bone growth in pediatric patients. Use with caution in patients with osteoporosis. In a population-based study of children, risk of fracture was shown to be increased with >4 courses of corticosteroids; underlying clinical condition may also impact bone health and osteoporotic effect of corticosteroids (Leonard 2007). In premature neonates, reports of gastrointestinal perforation in the hydrocortisone treatment arm have resulted in the closure of two large bronchopulmonary dysplasia (BPD) clinical trials (Peltoniemi 2005; Watterberg 2004); concomitant use with indomethacin or ibuprofen may increase the risk and should be avoided in this population (Seri 2006). Increased IOP may occur especially with prolonged use; in children, increased IOP has been shown to be dose dependent and produce a greater IOP in children <6 years than older children treated with ophthalmic dexamethasone (Lam 2005). Hypertrophic cardiomyopathy has been reported in premature neonates. In premature neonates, the use of high-dose dexamethasone (approximately >0.5 mg/kg/day) for the prevention or treatment of BPD has been associated with adverse neurodevelopmental outcomes, including higher rates of cerebral palsy without additional clinical benefit over lower doses; current data does not support use of high doses. Data specific to hydrocortisone use in this population has shown that use <7 days of therapy does not appear to be associated with adverse neurodevelopmental outcomes (Needelman 2010).
Substrate of CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Abrocitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Abrocitinib. Management: The use of abrocitinib in combination with other immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modification
Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Risk X: Avoid combination
Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy
Androgens: Corticosteroids (Systemic) may enhance the fluid-retaining effect of Androgens. Risk C: 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. Risk D: Consider therapy modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: 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. Risk D: Consider therapy modification
Axicabtagene Ciloleucel: Corticosteroids (Systemic) may diminish the therapeutic effect of Axicabtagene Ciloleucel. Management: Avoid use of corticosteroids as premedication before axicabtagene ciloleucel. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity. Risk D: Consider therapy modification
Baricitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Baricitinib. Management: The use of baricitinib in combination with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modification
BCG Products: Corticosteroids (Systemic) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Bile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Risk C: Monitor therapy
Brincidofovir: Corticosteroids (Systemic) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Calcitriol (Systemic): Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol (Systemic). Risk C: Monitor therapy
Cladribine: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Corticosteroids (Systemic) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing systemic corticosteroids (dosed at 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks) several weeks prior to coccidioides immitis skin antigen testing. Risk D: Consider therapy modification
Corticorelin: Corticosteroids (Systemic) may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
Cosyntropin: Hydrocortisone (Systemic) may diminish the diagnostic effect of Cosyntropin. Management: Patients receiving hydrocortisone should omit their pre-test dose on the day selected for cosyntropin testing. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Risk C: Monitor therapy
COVID-19 Vaccine (Inactivated Virus): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age or older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Hydrocortisone (Systemic). Risk C: 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. Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and systemic corticosteroids. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Desmopressin: Corticosteroids (Systemic) may enhance the hyponatremic effect of Desmopressin. Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Corticosteroids (Systemic). Management: Consider avoiding echinacea in patients receiving immunosuppressants, such as systemic corticosteroids. Doses more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modification
Estrogen Derivatives: May increase the serum concentration of Hydrocortisone (Systemic). Estrogen Derivatives may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Management: Reduce the dose of corticosteroids, such as dexamethasone or oral methylprednisolone, by 50% when coadministered with fosaprepitant. Reduce intravenous methylprednisolone doses by 25% during coadministration with fosaprepitant. Risk D: Consider therapy modification
Gallium Ga 68 Dotatate: Corticosteroids (Systemic) may diminish the diagnostic effect of Gallium Ga 68 Dotatate. Risk C: Monitor therapy
Growth Hormone Analogs: Corticosteroids (Systemic) may diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Corticosteroids (Systemic). Risk C: Monitor therapy
Hyaluronidase: Corticosteroids (Systemic) 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. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors: Corticosteroids (Systemic) may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modification
Indium 111 Capromab Pendetide: Corticosteroids (Systemic) may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Inebilizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiation of systemic corticosteroids at immunosuppressive doses. Influenza vaccines administered less than 14 days prior to or during such therapy should be repeated 3 months after therapy. Risk D: Consider therapy modification
Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid. Risk C: Monitor therapy
Leflunomide: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as systemic corticosteroids. Risk D: Consider therapy modification
Licorice: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Lutetium Lu 177 Dotatate: Corticosteroids (Systemic) may diminish the therapeutic effect of Lutetium Lu 177 Dotatate. Management: Avoid repeated use of high-doses of corticosteroids during treatment with lutetium Lu 177 dotatate. Use of corticosteroids is still permitted for the treatment of neuroendocrine hormonal crisis. The effects of lower corticosteroid doses is unknown. Risk D: Consider therapy modification
Macimorelin: Corticosteroids (Systemic) may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Mifamurtide: Corticosteroids (Systemic) may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination
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 (eg, for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Risk X: Avoid combination
Natalizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Natalizumab. Risk X: 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. Management: If concomitant therapy is required, use the lowest dose for the shortest duration to limit the risk of myopathy or neuropathy. Monitor for new onset or worsening muscle weakness, reduction or loss of deep tendon reflexes, and peripheral sensory decriments Risk D: Consider therapy modification
Nicorandil: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nicorandil. Gastrointestinal perforation has been reported in association with this combination. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Corticosteroids (Systemic). Specifically, the risk of gastrointestinal bleeding, ulceration, and perforation may be increased. Risk C: Monitor therapy
Ocrelizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Corticosteroids (Systemic) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Risk X: Avoid combination
Pneumococcal Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Polymethylmethacrylate. Specifically, the risk for hypersensitivity or implant clearance may be increased. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Quinolones: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased. Risk C: Monitor therapy
Rabies Vaccine: Corticosteroids (Systemic) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ritodrine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Ritodrine. Risk C: Monitor therapy
Rubella- or Varicella-Containing Live Vaccines: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
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. Risk C: Monitor therapy
Sargramostim: Corticosteroids (Systemic) may enhance the therapeutic effect of Sargramostim. Specifically, corticosteroids may enhance the myeloproliferative effects of sargramostim. Risk C: Monitor therapy
Sipuleucel-T: Corticosteroids (Systemic) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing immunosuppressants, such as systemic corticosteroids, prior to initiating sipuleucel-T therapy. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone given for 2 or more weeks are immunosuppressive. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Risk C: Monitor therapy
Succinylcholine: Corticosteroids (Systemic) may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Tacrolimus (Systemic): Corticosteroids (Systemic) may decrease the serum concentration of Tacrolimus (Systemic). Conversely, when discontinuing corticosteroid therapy, tacrolimus concentrations may increase. Risk C: Monitor therapy
Tacrolimus (Topical): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Corticosteroids (Systemic) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tisagenlecleucel: Corticosteroids (Systemic) may diminish the therapeutic effect of Tisagenlecleucel. Management: Avoid use of corticosteroids as premedication or at any time during treatment with tisagenlecleucel, except in the case of life-threatening emergency (such as resistant cytokine release syndrome). Risk D: Consider therapy modification
Tofacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modification
Typhoid Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Upadacitinib. Management: Coadministration of upadacitinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks. Risk D: Consider therapy modification
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. Risk C: Monitor therapy
Vaccines (Inactivated): Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Administer vaccines at least 2 weeks prior to immunosuppressive corticosteroids if possible. If patients are vaccinated less than 14 days prior to or during such therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. Risk D: Consider therapy modification
Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live vaccines during and for 1 month after therapy with immunosuppressive doses of corticosteroids (equivalent to prednisone > 2 mg/kg or 20 mg/day in persons over 10 kg for at least 2 weeks). Give live vaccines prior to therapy whenever possible. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Corticosteroids (Systemic) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Yellow Fever Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts or decreased birth weight; however, information is conflicting and may be influenced by maternal dose/indication for use (Lunghi 2010; Park-Wyllie 2000; Pradat 2003). Hypoadrenalism may occur in newborns following maternal use of corticosteroids in pregnancy; monitor.
When treating patients with adrenal insufficiency (primary or central or congenital adrenal hyperplasia) during pregnancy, hydrocortisone is the preferred corticosteroid. Doses may need to be adjusted as pregnancy progresses. Pregnant patients with adrenal insufficiency should be monitored at least once each trimester (ES [Bornstein 2016]; ES [Fleseriu 2016]; ES [Speiser 2018]).
High doses of hydrocortisone (ie, stress doses) may be required to prevent adrenal crisis during labor in patients with known or suspected adrenal insufficiency (eg, Cushingoid appearance, prolonged glucocorticoid therapy) (ES [Bornstein 2016]; ES [Fleseriu 2016]; ES [Speiser 2018]). Patients who require systemic corticosteroids for management of asthma should also be given IV corticosteroids, such as hydrocortisone, during labor and for 24 hours after delivery to prevent adrenal crisis (ACOG [Dombrowski 2008]; ERS/TSANZ [Middleton 2020]). Patients using chronic low dose steroids for rheumatic disorders generally do not need a stress dose of hydrocortisone at the time of vaginal delivery; however, stress dosing may be needed in women with multiple comorbidities treated with chronic high dose steroid therapy. Stress dosing is recommended prior to cesarean delivery (ACR [Sammaritano 2020]).
Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes). Maternal asthma symptoms should be monitored monthly during pregnancy. Inhaled corticosteroids are recommended for the treatment of asthma during pregnancy; however, systemic corticosteroids should be used to control acute exacerbations or treat severe persistent asthma. Hydrocortisone may be used when parenteral administration is required (ERS/TSANZ [Middleton 2020]; GINA 2020).
Hydrocortisone is approved for the treatment of rheumatic disorders, however, when systemic corticosteroids are needed in pregnancy, nonfluorinated corticosteroids (eg, prednisone) are preferred (ACR [Sammaritano 2020]).
For dermatologic disorders in pregnant women, systemic corticosteroids are generally not preferred for initial therapy; should be avoided during the first trimester; and used during the second or third trimester at the lowest effective dose (Bae 2012; Leachman 2006).
In nonpregnant patients, hydrocortisone is recommended off label as an alternative corticosteroid for the management of COVID-19 (NIH 2021). Hydrocortisone is also an alternative for use in pregnant patients with severe or critical COVID-19 due to limited placental transfer. A treatment algorithm is available for pregnant patients with severe or critical COVID-19; the algorithm differentiates recommendations based on the patient's requirement for corticosteroids for fetal lung maturation. Close glucose monitoring is recommended (Saad 2020). The risk of severe illness from COVID-19 infection is increased in pregnant patients. Pregnancy is considered a high-risk medical condition by the CDC (ACOG 2021). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.
Corticosteroids are present in breast milk.
The manufacturer notes that when used systemically, maternal use of corticosteroids have the potential to cause adverse events in a breastfed infant (eg, growth suppression, interfere with endogenous corticosteroid production). Single doses of hydrocortisone are considered acceptable for use in breastfeeding females; data is not available following prolonged use. Corticosteroids are generally considered acceptable in breastfeeding females when used in usual doses; however, monitoring of the infant is recommended (WHO 2002).
If there is concern about exposure to the infant, some guidelines recommend waiting 4 hours after the maternal dose of an oral systemic corticosteroid before breastfeeding in order to decrease potential exposure to the breastfed infant (based on a study using prednisolone) (ACR [Sammaritano 2020]; Bae 2012; Butler 2014; ERS/TSANZ [Middleton 2020]; Leachman 2006; Ost 1985).
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.
Serum glucose, electrolytes; BP, 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); signs and symptoms of behavioral or mood changes; signs and symptoms of Cushing syndrome every 6 months (pediatric patients <1 year of age may require monitoring every 3 to 4 months); growth in pediatric patients.
Short-acting corticosteroid with minimal sodium-retaining potential; decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability
Onset of action: IV: 1 hour.
Absorption: Rapid.
Bioavailability: Oral: 96% ± 20% (Czock 2005); oral sprinkles: ~87%.
Distribution: Vd: IV: 27 ± 7 L (Czock 2005).
Protein binding: IV: 92% ± 2% (Czock 2005); oral sprinkles: ≥90%.
Metabolism: Hepatic.
Half-life elimination: IM: 2.2 ± 1.5 hours (Hahner 2013); IV: 2 ± 0.3 hours; Oral: 1.8 ± 0.5 hours (Czock 2005); SubQ: 4.7 ± 4.7 hours (Hahner 2013).
Time to peak, plasma: IM: 66 ± 51 minutes (Hahner 2013); Oral: 1.2 ± 0.4 hours (Czock 2005); SubQ: 91 ± 34 minutes (Hahner 2013).
Excretion: Urine (Czock 2005).
Capsule, sprinkles (Alkindi Sprinkle Oral)
0.5 mg (per each): $8.89
1 mg (per each): $17.77
2 mg (per each): $35.55
5 mg (per each): $88.87
Solution (reconstituted) (Solu-CORTEF Injection)
100 mg (per each): $22.21
250 mg (per each): $41.09
500 mg (per each): $82.20
1000 mg (per each): $164.38
Tablets (Cortef Oral)
5 mg (per each): $1.21
10 mg (per each): $2.04
20 mg (per each): $3.86
Tablets (Hydrocortisone Oral)
5 mg (per each): $0.34 - $1.02
10 mg (per each): $0.57 - $1.72
20 mg (per each): $1.09 - $3.26
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