Hydrocortisone (Systemic)

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])

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

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

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)

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); 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: 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.

Frequency not defined.

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

Central nervous system: Arachnoiditis (intrathecal administration), depression, emotional lability, euphoria, headache, increased intracranial pressure (with pseudotumor cerebri; usually following discontinuation), insomnia, malaise, meningitis (intrathecal administration), myasthenia, neuritis, neuropathy, paraplegia (intrathecal administration), paresthesia, personality changes, psychic disorder, seizure, sensory disturbance (intrathecal administration), tingling of skin (especially in the perineal area after IV injection), vertigo

Dermatologic: Acne vulgaris, allergic dermatitis, alopecia, atrophic striae, burning sensation of skin (especially in the perineal area after IV injection), diaphoresis, ecchymosis, erythema (including facial), exfoliation of skin, hyperpigmentation, hypertrichosis, hypopigmentation, skin atrophy, skin rash, suppression of skin test reaction, urticaria, xeroderma

Endocrine & metabolic: Adrenal suppression, Cushing syndrome, diabetes mellitus (latent), fluid retention, glycosuria, growth suppression, hirsutism, HPA-axis suppression, hypercalcemia (associated with cancers), hyperglycemia (including increased requirements for insulin or oral hypoglycemic agents in diabetes mellitus), hypokalemia, hypokalemic alkalosis, impaired glucose tolerance, lipodystrophy, lipomatosis (epidural), menstrual disease (menstrual irregularities), moon face, negative nitrogen balance, protein catabolism, sodium retention, weight gain

Gastrointestinal: Abdominal distention, carbohydrate intolerance, dyspepsia, gastrointestinal disease (intrathecal administration), gastrointestinal perforation (small and large intestine, particularly in patients with inflammatory bowel disease), hiccups, increased appetite, nausea, pancreatitis, peptic ulcer (with possible perforation and hemorrhage), ulcerative esophagitis, vomiting

Genitourinary: Asthenospermia, bladder dysfunction (intrathecal administration)

Hematologic & oncologic: Leukocytosis, petechia

Hepatic: Hepatomegaly, increased serum transaminases (usually mild elevations and reversible on discontinuation)

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction

Infection: Increased susceptibility to infection, infection, sterile abscess

Local: Atrophy at injection site (cutaneous and subcutaneous), postinjection flare (intra-articular use), skin edema

Neuromuscular & skeletal: Amyotrophy, Charcot-like arthropathy, lower extremity weakness (intrathecal administration), osteonecrosis (aseptic necrosis of femoral and humoral heads), osteoporosis, pathological fracture (long bones), rupture of tendon (particularly Achilles tendon), steroid myopathy, vertebral compression fracture

Ophthalmic: Cataract (posterior subcapsular), exophthalmos, glaucoma, increased intraocular pressure, retinopathy (central serous chorioretinopathy)

Respiratory: Pulmonary edema

Miscellaneous: Wound healing impairment

<1% (Limited to important or life-threatening): Anaphylactoid reaction, blindness (periocular injection)

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 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).

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).

• 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.