Hydrocortisone Sodium Succinate (Solu-Cortef)

1. Health Canada Product Monograph — Hydrocortisone Sodium Succinate

• Used as replacement therapy in primary, secondary, or acute adrenal insufficiency, congenital adrenal hyperplasia, and related endocrine conditions.
• Used short-term as adjunctive therapy for acute flares of rheumatic conditions such as rheumatoid arthritis, gouty arthritis, bursitis, and ankylosing spondylitis.
• Used during exacerbations of collagen-vascular diseases such as systemic lupus erythematosus and dermatomyositis.
• Used for severe dermatologic conditions such as pemphigus, severe erythema multiforme, exfoliative dermatitis, and severe psoriasis.
• Used to control severe allergic conditions that have not responded to conventional treatment, including severe asthma, contact and atopic dermatitis, serum sickness, and drug hypersensitivity reactions.
• Used for severe inflammatory eye conditions such as uveitis and optic neuritis.
• Used to help patients through critical periods of ulcerative colitis or regional enteritis.
• Used for certain respiratory conditions including sarcoidosis and, together with antituberculous therapy, severe or disseminated tuberculosis.
• Used for select hematologic and oncologic conditions, including autoimmune hemolytic anemia and as palliative therapy in leukemia or lymphoma.
• Used to induce diuresis or remission of protein loss in nephrotic syndrome.
• Used as emergency treatment for shock related to adrenal insufficiency and as an adjunct to epinephrine in severe acute allergic reactions.

• Corticosteroids cross the placenta readily and have been shown to cause birth defects such as cleft palate in several animal species at doses comparable to those used in humans, although congenital anomalies have not been clearly established in human pregnancies.
• Retrospective studies suggest a dose-related increase in low birth weight with corticosteroid use in pregnancy, and cataracts have been observed in infants of mothers treated with long-term corticosteroids during pregnancy, so Solu-Cortef should be used in pregnancy only at the lowest effective dose and only when clearly needed.
• Infants born to mothers who received substantial corticosteroid doses during pregnancy should be carefully observed for signs of adrenal insufficiency.

• Systemically administered corticosteroids are excreted into breast milk and may suppress infant growth, interfere with the infant's own corticosteroid production, or cause other unwanted effects, so a careful assessment of the benefit to the mother against the risk to the nursing infant should guide whether nursing or the drug should be discontinued.

• Dose selection in older adults should be cautious, generally starting at the low end of the dosing range, reflecting the greater likelihood of reduced liver, kidney, or heart function and of other concurrent illness or medications in this age group.

• Dosing in infants and children is guided more by the severity of the condition being treated and the patient's response than by age or body weight alone, though the daily dose is generally not less than 25 mg.
• Children on prolonged corticosteroid therapy should have their growth and development closely monitored, along with blood pressure, weight, height, eye pressure, and screening for infection, psychological effects, peptic ulcers, and bone loss, since growth velocity can be affected even at low systemic doses.
• Very young or premature infants receiving hydrocortisone have developed thickening of the heart muscle (hypertrophic cardiomyopathy), so cardiac structure and function should be evaluated and monitored in this population.

• The initial dose typically ranges from 100 mg to 500 mg or more depending on the severity of the condition, given by intravenous injection over 30 seconds to 10 minutes, and may be repeated every 2, 4, or 6 hours based on the patient's response.
• High-dose therapy is generally continued only until the patient's condition has stabilized, usually no more than 48 to 72 hours, after which a longer-acting injectable or oral corticosteroid is typically substituted.
• It may be given by intravenous injection, intravenous infusion, or deep intramuscular injection into a large muscle mass, with intravenous injection preferred for initial emergency treatment.
• The powder must be reconstituted using the two-compartment Act-O-Vial system immediately before use, and any unused reconstituted or diluted solution should be discarded rather than stored for later use.
• If corticosteroid therapy is being stopped after a prolonged course, the dose must be tapered down gradually rather than stopped abruptly.

• Increased appetite and weight gain may occur.
• Fluid retention and mild swelling may occur.
• Elevated blood pressure may occur.
• Difficulty sleeping, mood changes, or nervousness may occur.
• Indigestion or stomach upset may occur.
• Headache may occur.
• A burning or tingling sensation, particularly in the perineal area, may occur briefly during or after intravenous injection.
• Slowed wound healing may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Suppression of the body's own adrenal hormone production can occur with prolonged use, creating a risk of adrenal insufficiency if the drug is stopped abruptly.
• Cushingoid changes, such as a rounded face, abnormal fat redistribution, and excess hair growth, can develop with prolonged use.
• Elevated blood sugar and worsening of pre-existing diabetes can occur.
• Bone thinning (osteoporosis) and fractures, including spinal compression fractures, can develop with long-term therapy.
• Muscle weakness or breakdown (myopathy or rhabdomyolysis) can occur, especially with high doses or in patients with neuromuscular disease.
• Peptic ulcer disease, including bleeding or perforation, and pancreatitis can occur, particularly when combined with anti-inflammatory painkillers.
• Increased susceptibility to infection can occur, and corticosteroids can mask the usual signs of an infection or of organ perforation.
• Psychiatric reactions ranging from mood swings and insomnia to severe depression, mania, or psychosis, including suicidal thinking, can occur.
• Heart failure, arrhythmia, and rare cases of cardiac arrest or heart enlargement have been reported, particularly with rapid high-dose administration in very young infants.
• Blood clots, including deep vein thrombosis and pulmonary embolism, have been reported.
• Eye problems such as cataracts, glaucoma, elevated eye pressure, and rare vision loss can occur with prolonged use.
• Serious allergic reactions, including anaphylaxis and swelling of the face or throat, can occur.
• Thinning of the skin and tissue at the injection site can occur, particularly with repeated intramuscular injections or if the deltoid muscle is used.
• Tendon rupture has been reported with corticosteroid use.
• Increased pressure inside the skull, most often noticed after stopping treatment, can occur.
• Seizures can occur, especially in patients with a predisposing condition.

• Use with caution in patients with diabetes, osteoporosis, kidney impairment, chronic psychosis, high blood pressure, myasthenia gravis, or a tendency toward blood clots.
• Use with caution in patients with heart failure or who have recently had a heart attack, since there is a reported association between corticosteroid use and rupture of the heart wall after a recent infarction.
• Use with caution in patients with active or prior peptic ulcer disease, diverticulitis, recent bowel surgery, or inflammatory bowel disease, since corticosteroids may increase the risk of perforation.
• Use with caution in patients with latent tuberculosis or a positive tuberculin test, since reactivation of the disease is possible.
• Use with caution in patients with active eye infection from herpes simplex, due to the risk of corneal damage.
• Use with caution in patients with a seizure disorder.
• Use with caution in patients with an underactive thyroid, since the effects of corticosteroids are enhanced in this condition.
• Use with caution in patients with significant liver impairment or cirrhosis, since corticosteroid clearance is reduced and effects may be prolonged.
• Should not be injected into a joint, bursa, or tendon sheath in the presence of an active local infection.

• Contraindicated in patients with known hypersensitivity to hydrocortisone sodium succinate or any other ingredient in the product.
• Contraindicated in patients with systemic fungal infections.
• Contraindicated for intramuscular administration in patients with idiopathic thrombocytopenic purpura.
• Contraindicated for use with live or live attenuated vaccines in patients receiving immunosuppressive corticosteroid doses.
• Contraindicated in active herpes simplex infection of the eye, except for short-term or emergency use in acute allergic reactions.
• Contraindicated in vaccinia or varicella (chickenpox) infection, except for short-term or emergency use in acute allergic reactions.
• Not intended for epidural administration, and intrathecal administration is contraindicated except as part of certain chemotherapy protocols, since serious events including death have been associated with these routes.

• Drugs that inhibit the CYP3A4 liver enzyme, such as ketoconazole, itraconazole, clarithromycin, erythromycin, diltiazem, cyclosporine, and certain antiviral protease inhibitors, can slow hydrocortisone clearance and increase its blood levels, so a lower corticosteroid dose may be needed.
• Drugs that induce the CYP3A4 enzyme, such as rifampin, carbamazepine, phenytoin, and barbiturates, can speed up hydrocortisone clearance and reduce its effectiveness, so a higher dose may be required.
• Effects on warfarin and other vitamin K antagonist anticoagulants can be unpredictable, with reports of both increased and decreased anticoagulant effect, so coagulation tests should be monitored closely.
• Corticosteroids can raise blood glucose, so dosage adjustments of insulin or oral antidiabetic medications may be needed.
• Combined use with digoxin can raise the risk of irregular heart rhythm due to corticosteroid-induced potassium loss, so electrolytes should be monitored.
• Cholestyramine may increase the clearance of corticosteroids from the body.
• Estrogen-containing products, including oral contraceptives, may increase corticosteroid effect by raising the level of the protein that carries corticosteroids in the blood.
• Combined use with NSAIDs or high-dose aspirin increases the risk of stomach ulcers and gastrointestinal bleeding.
• Combined use with potassium-lowering diuretics or amphotericin B increases the risk of low blood potassium, and cases of heart enlargement and heart failure have been reported with concurrent amphotericin B use.
• Corticosteroids can blunt the immune response to vaccines and should generally not be given with live vaccines during immunosuppressive dosing.
• Combined use with neuromuscular blocking drugs has been associated with prolonged muscle weakness (acute myopathy), and corticosteroids may alter the effect of these agents.
• Combined use with anticholinesterase drugs in patients with myasthenia gravis can cause severe muscle weakness.

• Grapefruit juice inhibits the same liver enzyme that clears hydrocortisone and could theoretically raise its blood levels, though this has limited practical relevance for a short-course injectable medication given in a hospital or clinic setting.

• Administered by a healthcare professional as an intravenous injection, intravenous infusion, or intramuscular injection, with the dosing interval (commonly every 2, 4, or 6 hours) determined by the treating physician based on the patient's condition.

• Store the unreconstituted powder at room temperature, between 15 and 30 degrees C.
• Once reconstituted, store at room temperature protected from light, use only if the solution is clear, and discard any unused portion, since the Act-O-Vial is intended for single-dose use.

• Solu-Cortef is a fast-acting injectable corticosteroid used in the hospital or clinic to treat severe inflammatory, allergic, adrenal, or emergency conditions.
• It is given by injection or infusion by a healthcare professional, with the dose and schedule determined by your medical team based on your specific condition.
• Common effects can include increased appetite, mild fluid retention, trouble sleeping, or indigestion.
• Tell your care team right away about signs of infection, unusual mood or behavior changes, vision changes, severe stomach pain, black or bloody stools, unusual muscle weakness, or swelling of the face or throat.
• This medication should never be stopped abruptly after more than a few days of use; your medical team will taper the dose gradually if treatment is being discontinued.
• Let your healthcare team know if you are pregnant, breastfeeding, or have diabetes, a stomach ulcer, a recent infection, or any heart, liver, or kidney condition before treatment begins.