Methylprednisolone

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.

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

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.

High doses of methylprednisolone IV (usually doses of 1 g/day) may induce a toxic form of acute hepatitis (rare); serious hepatic injury may occur, resulting in acute liver failure and death. Time to onset can be several weeks or longer; resolution has been observed after discontinuation of therapy. Discontinue methylprednisolone if toxic hepatitis occurs. Avoid use of high doses in patients with a history of methylprednisone-induced toxic hepatitis.

Prolonged use of corticosteroids may increase the incidence of secondary infection, cause activation of latent infections, mask acute infection (including fungal infections), prolong or exacerbate viral or parasitic infections, or limit response to killed or inactivated vaccines. Exposure to chickenpox or measles should be avoided; corticosteroids should not be used to treat ocular herpes simplex. 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). Amebiasis should be ruled out in any patient with recent travel to tropic climates or unexplained diarrhea prior to initiation of corticosteroids. Use with extreme caution in patients with Strongyloides infections; hyperinfection, dissemination and fatalities have occurred.

Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); discontinuation may result in clinical improvement (Goedert 2002).

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.

Corticosteroid use may cause psychiatric disturbances, including euphoria, insomnia, mood swings, personality changes, severe depression, or psychotic manifestations. Preexisting psychiatric conditions may be exacerbated by corticosteroid use.

May occur as a complication to parenteral therapy; institute appropriate antimicrobial therapy as required. Disease-related concerns:

Use with caution in patients with heart failure (HF) and/or hypertension; use has been associated with fluid retention, electrolyte disturbances, and hypertension. Use with caution following acute myocardial infarction (MI); corticosteroids have been associated with myocardial rupture.

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

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.

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

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

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

Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Not recommended for the treatment of optic neuritis; may increase frequency of new episodes. Use with caution in patients with a history of ocular herpes simplex; corneal perforation has occurred; do not use in active ocular herpes simplex. Consider routine eye exams in chronic users.

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.

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

Use with caution in patients with systemic sclerosis; an increase in scleroderma renal crisis incidence has been observed with corticosteroid use.

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

A study has failed to demonstrate efficacy in septic shock or sepsis syndrome treatment; use may increase mortality in some populations (eg, patients with elevated serum creatinine, patients who develop secondary infections after use).

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

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:

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

May affect growth velocity; growth should be routinely monitored in pediatric patients. Dosage form specific issues:

Methylprednisolone acetate IM injection (multiple-dose vial) and the diluent for methylprednisolone sodium succinate injection may contain 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 with caution in neonates. See manufacturer’s labeling.

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling. Other warnings/precautions:

Withdraw therapy with gradual tapering of dose.

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.

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