Glucocorticoids are responsible for protein metabolism, and prolonged therapy can result in various musculoskeletal manifestations, including: myopathy (myalgia, muscle wasting, muscle weakness, quadriparesis), impaired wound healing, bone matrix atrophy (osteoporosis), bone fractures such as vertebral compression fractures or fractures of long bones, and avascular necrosis of femoral or humoral heads. These effects are more likely to occur in older or debilitated patients. Glucocorticoids interact with calcium metabolism at many sites, including: calcinosis, decreasing the synthesis by osteoblasts of the principle proteins of bone matrix, malabsorption of calcium in both the nephron and the gut, and reduction of sex hormone concentrations. Although all of these actions probably contribute to glucocorticoid-induced osteoporosis, the actions on osteoblasts is most important. Glucocorticoids do not modify vitamin D metabolism.[24837] Postmenopausal women, in particular, should be monitored for signs of osteoporosis during methylprednisolone therapy. Because of retardation of bone growth, children receiving prolonged corticosteroid therapy may have growth inhibition. Intra-articular injections of corticosteroids can cause Charcot-like arthropathy and postinjection flare. Atrophy at the site of injection has been reported following administration of soluble glucocorticoids. Tendon rupture has also been reported.[30015] [41361] [41362]

Methylprednisolone can mask the symptoms of infection and should be avoided during an acute viral, fungal, or bacterial infection; as well, patients receiving corticosteroids are more susceptible to infections than are healthy individuals. Leukocytosis has been reported and is a common physiologic effect of systemic corticosteroid therapy and may need to be differentiated from the leukocytosis that occurs with inflammatory or infectious processes.[30943] [65096] [65097] Immunosuppression is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily), systemic corticosteroid therapy for any period of time, particularly in conjunction with corticosteroid-sparing drugs (e.g., troleandomycin) and/or concomitant immunosuppressant agents; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods also may be at risk. Corticosteroids can reactivate tuberculosis and should not be used in patients with a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to measles or varicella (chickenpox) and, if exposed to these diseases, to seek medical advice immediately.[30015] [41361] [41362]

Corticosteroids are divided into two classes: mineralocorticoids and glucocorticoids. Methylprednisolone is a glucocorticoid with minimal mineralocorticoid activity. Mineralocorticoids alter electrolyte and fluid balance by facilitating sodium retention and hydrogen and potassium excretion at the level of the distal renal tubule, resulting in increased plasma volume. Although the incidence of effects with this medication are not well elicited, mineralocorticoid properties can cause fluid retention; electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia); and edema. In a review of 93 studies of corticosteroid use, hypertension was found to develop approximately 4 times as often in steroid recipients compared to control groups.[24362] As a result of the steroid-induced edema and elevated blood pressure, congestive heart failure can occur in susceptible patients. Dietary salt restriction and potassium supplementation may be needed in persons receiving treatment with methylprednisolone.[30015] [41361] [41362]

Cardiovascular adverse events have been reported during and/or after treatment with parenteral methylprednisolone. These adverse events include bradycardia, cardiac arrest, cardiac arrhythmia exacerbation, cardiac failure, cardiomegaly, fat (lipid) emboli, hypertrophic cardiomyopathy (in premature infants), pulmonary edema, sinus tachycardia, syncope, and vasculitis. Additionally, corticosteroid therapy has also been associated with ruptures of the left ventricular free wall in persons having recently experienced a myocardial infarction; thus, caution is advised when prescribing methylprednisolone to these patients.[41361] [41362]

Although corticosteroids are used to treat Graves' ophthalmopathy, ocular effects, such as exophthalmos, posterior subcapsular cataracts, retinopathy, or ocular hypertension, can result from prolonged use of methylprednisolone and could result in glaucoma or ocular nerve damage including optic neuritis. Temporary or permanent visual impairment, including blindness, has been reported with glucocorticoid administration by several routes of administration including intranasal and ophthalmic administration. Secondary bacterial, fungal, and viral ocular infection can be exacerbated by corticosteroid therapy. Corneal perforation may occur if corticosteroids are administered to patients with ocular herpes simplex and, thus, should not be used during active ocular herpes simplex infection.[30015] [41361] [41362]

Prolonged therapy of methylprednisolone can adversely affect the endocrine system, resulting in hypercorticism (Cushing's syndrome), menstrual irregularity including amenorrhea or dysmenorrhea, and decreased carbohydrate and glucose tolerance.[30015] [41361] [41362] Systemic corticosteroids are a common cause of drug-induced hyperglycemia. In the hospital setting, there is evidence that more than 50% of the patients receiving high-dose systemic steroids develop hyperglycemia, with many more having at least 1 episode of hyperglycemia or a mean blood glucose of 140 mg/dL or greater. Long-term use produces metabolic and endocrine effects that include insulin resistance that may lead to new diagnoses of diabetes mellitus (DM) in patients without a history of hyperglycemia or DM prior to corticosteroid use. Glucosuria (glycosuria) and aggravation of existing diabetes mellitus may also occur.[68700]

Adverse GI effects associated with long-term corticosteroid administration include nausea, vomiting, and anorexia. Appetite stimulation with weight gain, diarrhea, constipation, abdominal pain and distention, esophageal ulceration, gastritis, GI perforation, and pancreatitis also have been reported. A few patients receiving prolonged corticosteroid administration have experienced production, reactivation, perforation, or delayed healing of peptic ulcer disease. Although it was once believed that corticosteroids like methylprednisolone contributed to the development of peptic ulcer disease, in a published review of 93 studies of corticosteroid use, the incidence of peptic ulcer disease was not found to be higher in steroid recipients compared to control groups.[24362] Cases of hepatomegaly and elevated hepatic enzymes (reversible upon discontinuation) have been associated with the use of methylprednisolone.[30015] [41361] [41362] Rarely, high doses of cyclically pulsed IV methylprednisolone can induce a toxic form of acute hepatitis. This may occur several weeks after exposure and resolution has been observed after treatment is discontinued. However, serious liver injury may occur, which could result in acute hepatic failure and death. Discontinue IV methylprednisolone if toxic hepatitis occurs. Avoid future use of high dose IV methylprednisolone in patients with toxic hepatitis caused by methylprednisolone.[41361]

Adverse neurologic effects have been reported with methylprednisolone and other corticosteroid administration include headache, insomnia, vertigo, restlessness, ischemic peripheral neuropathy, neuritis, seizures or convulsions, and EEG changes. Methylprednisolone and other systemic corticosteroids may cause mood swings (emotional lability) and psychiatric side effects; irritability, depression, euphoria, changes in mood and behavior, personality changes and psychosis have been reported.[30015] [41361] [41362] [68690] [68691]

Various adverse dermatologic effects reported during corticosteroid therapy include rash (unspecified), skin atrophy, dry skin or xerosis, acne vulgaris, alopecia or thinning scalp hair, diaphoresis, impaired wound healing, facial erythema, striae, petechiae, hirsutism or hypertrichosis, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, anaphylactoid reactions, and/or angioedema.[30015] Paresthesias (burning or tingling) in the perineal area may occur following IV injection of corticosteroids like methylprednisolone. Parenteral corticosteroid therapy has also produced skin hypopigmentation, skin hyperpigmentation, scarring, and other types of injection site reaction (e.g., induration, delayed pain or soreness, subcutaneous and cutaneous atrophy, and sterile abscesses); use via incorrect route of administration and/or excessive doses may increase risk of such effects.[41361] [41362]

Pharmacologic doses of methylprednisolone administered for prolonged periods can result in physiological dependence due to hypothalamic-pituitary-adrenal (HPA) suppression. Exogenous corticosteroids exert negative feedback on the pituitary, inhibiting the secretion of adrenocorticotropin (ACTH). This inhibition decreases ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The severity of glucocorticoid-induced secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time of administration, and duration of therapy. Administering the drug on alternate days may help to alleviate this adverse effect. Patients with HPA suppression will require increased doses of corticosteroids during periods of physiologic stress. Acute adrenal insufficiency and even death can occur if sudden withdrawal of the drugs is undertaken. Withdrawal from prolonged oral corticosteroid therapy should be gradual; HPA suppression can last for up to 12 months following cessation of therapy, and patients may need supplemental corticosteroid treatment during periods of physiologic stress such as surgery, acute blood loss, or infection, even after the drug has been discontinued. A non-HAP withdrawal syndrome can occur following abrupt discontinuance of corticosteroid therapy and is apparently unrelated to adrenocortical insufficiency. This syndrome includes symptoms such as anorexia, lethargy, nausea, vomiting, headache, fever, arthralgia, myalgia, exfoliative dermatitis, weight loss, and hypotension. These effects are believed to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels. Increased intracranial pressure with papilledema (i.e., pseudotumor cerebri) has also been reported with withdrawal of glucocorticoid therapy.[30015] [41361] [41362]

Hypercholesterolemia, atherosclerosis, fat (lipid) emboli, thrombosis, thromboembolism, and phlebitis, specifically, thrombophlebitis have been associated with corticosteroid therapy. Other adverse events reported during treatment with corticosteroids include abnormal fat deposits (moon face), hiccups, malaise, and changes (increase or decrease) in the motility and number of spermatozoa. Palpitations, glossitis, stomatitis, urinary incontinence, and urinary urgency have been rarely reported. Corticosteroids like methylprednisolone may also decrease serum concentrations of vitamin C (ascorbic acid) and vitamin A which may rarely produce symptoms of vitamin A deficiency or vitamin C deficiency.[30015] [41361] [41362]

The Solu-Medrol 40 mg presentation contains lactose monohydrate produced from cow's milk. In situations where allergic symptoms worsen or new allergic symptoms occur after administration of this preparation, consider the potential for hypersensitivity reactions to cow's milk ingredients. Additionally, lactose intolerance symptoms such as nausea/vomiting, bloating, abdominal pain (cramps), and flatulence may occur. Use appropriate precautions when administering to patients with a cow's milk sensitivity or lactose intolerance. If hypersensitivity reactions occur with the Solu-Medrol 40 mg presentation, consider discontinuing treatments and using alternative treatments, including corticosteroid formulations that do not contain ingredients produced from cow's milk.[41361]

An increased incidence of scleroderma renal crisis (SRC) has been observed in patients with systemic sclerosis (systemic scleroderma) treated with corticosteroids. SRC is characterized by malignant hypertension and acute renal failure (unspecified) that may be accompanied by oliguria or anuria.[30015] [41361] [41362]

Tumor lysis syndrome (TLS) has been reported during postmarketing surveillance of systemic corticosteroids alone or in combination with other chemotherapeutic agents in patients with malignancies, including hematological malignancies and solid tumors. Patients at high risk of TLS, such as patients with tumors that have a high proliferative rate, high tumor burden and high sensitivity to cytotoxic agents, should be monitored closely and appropriate precautions should be taken.[30015] [41362] [41361]

Methylprednisolone is contraindicated in patients with a hypersensitivity to methylprednisolone or any components of the selected product.[30015] [41361] [41362] [30015] True corticosteroid hypersensitivity reactions are rare; however, rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy. While a hypersensitivity reaction could be to a specific salt of the corticosteroid, administer any form of methylprednisolone with extreme caution in patients who have demonstrated a prior hypersensitivity reaction to methylprednisolone. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Carefully monitor such patients during and after the administration of any corticosteroid.[27616] [27642] [55730] Some methylprednisolone sodium succinate injection presentations (i.e., Solu-Medrol brand, 40 mg injection) contain lactose monohydrate produced from cow's milk and thus are contraindicated in patients with a known or suspected hypersensitivity to cow's milk (milk protein hypersensitivity), milk components, or other dairy products.[41361]

Systemic corticosteroids, including methylprednisolone, may cause immunosuppression and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: 1) Reduce resistance to new infections, 2) Exacerbate existing infections, 3) Increase the risk of disseminated infections, 4) Increase the risk of reactivation or exacerbation of latent infections 5) Mask some signs of infection. Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider corticosteroid withdrawal or dosage reduction as needed. Do not administer methylprednisolone injections by an intraarticular, intrabursal, iintratendinous, or intralesional route in the presence of acute local infection. If methylprednisolone is used to treat a condition in patients with latent tuberculosis (TB) or tuberculin reactivity, reactivation of TB may occur. Closely monitor such patients for TB reactivation. During prolonged methylprednisolone therapy, patients with latent TB or tuberculin reactivity should receive chemoprophylaxis. Viral infection, such as varicella zoster (chickenpox or shingles) and measles can have a serious or even fatal course in non-immune patients taking corticosteroids; other herpes infection (herpes simplex) may also disseminate in immunosuppressed individuals. In corticosteroid-treated patients who have not had these diseases or are nonimmune, avoid exposure of these people to these viral infections. If a corticosteroid-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If varicella develops, consider treatment with antiviral. If a corticosteroid-treated patient is exposed to measles, prophylaxis with immunoglobulin (IG) may be indicated. Hepatitis B exacerbation/reactivation can occur in patients who are hepatitis B virus carriers treated with immunosuppressive dosages of corticosteroids, including methylprednisolone. Reactivation can also occur infrequently in corticosteroid-treated people who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with systemic corticosteroids. For individuals who show evidence of hepatitis B infection, consult providers with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy. Systemic methylprednisolone use is generally contraindicated in the presence of a systemic fungal infection. Corticosteroids, including methylprednisolone, may exacerbate systemic fungal infections; therefore, avoid corticosteroid use in the presence of a fungal infection unless a corticosteroid is needed to control drug reactions. If a fungal infection develops during chronic corticosteroid therapy, corticosteroid withdrawal or dosage reduction is recommended. Depot methylprednisolone acetate injection is contraindicated for use in systemic fungal infections, except when administered as an intra-articular injection for localized joint conditions. Corticosteroids, including methylprednisolone, may activate latent amebiasis. Latent or active amebiasis should be ruled out before initiating methylprednisolone in people who have spent time in the tropics or have unexplained diarrhea. Corticosteroids, including methylprednisolone, should be used with great care in the presence of known or suspected Strongyloides (threadworm) helminth infection. Corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. In selected patients from strongyloidiasis endemic areas who need systemic corticosteroids, consider administering prophylactic treatment. Also avoid corticosteroids, including methylprednisolone, in people with cerebral malaria. 30015] [41361] [41362]

Systemic effects of corticosteroids may result in hypothalamic-pituitary-adrenal (HPA) suppression and/or manifestations of Cushing's syndrome in some patients. Adrenocortical insufficiency, adrenal crisis, and death may occur after abrupt discontinuation of prolonged systemic therapy. Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of systemic corticosteroids in pediatric patients. Adrenal crisis may also be induced by stressful events such as infections or surgery; patients may require higher doses of corticosteroids during times of stress. Symptoms of adrenocortical insufficiency include poor feeding, fatigue, low muscle tone, joint pain, nausea, vomiting, hypoglycemia, low blood pressure, and electrolyte disturbances. Switch patients unable to take oral medications (i.e., severely ill or vomiting) to parenteral corticosteroid formulations until recovered. Once oral medications are tolerated, gradually reduce the steroid dosage during the acute event. A withdrawal syndrome unrelated to adrenocortical insufficiency may occur after sudden discontinuation of corticosteroid therapy. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid concentrations. Withdrawal from prolonged systemic corticosteroid therapy should be gradual. HPA suppression can last for up to 12 months following cessation of systemic therapy. HPA-suppressed patients may need supplemental corticosteroid treatment during periods of physiologic stress, such as surgical procedures, acute blood loss, or infection, even after the corticosteroid has been discontinued. Encourage patients currently receiving chronic corticosteroid therapy or who have had corticosteroids discontinued within the last 12 months to carry identification advising the need for administration of methylprednisolone in situations of increased stress.[30015] [41361] [41362]

Use of methylprednisolone is contraindicated for intrathecal administration.[41361] [41362] Do not give methylprednisolone acetate suspension injection via intravenous administration.[41362] The safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use. Severe adverse medical events have occurred following administration of parenteral methylprednisolone via an incorrect route; to minimize the incidence of adverse events, care must be taken to administer the drug as intended and to not exceed recommended doses in each injection.[41361] [41362] [57052] Rare, but serious adverse neurologic events, including cortical blindness, stroke, spinal cord infarction, paralysis, seizures, nerve injury, brain edema, and death have been reported after epidural administration of corticosteroid injections. These events have been reported with and without the use of fluoroscopy. Many cases were temporally associated with the corticosteroid injections; adverse reactions occurred within minutes to 48 hours after the corticosteroid injections. Some cases of neurologic events were confirmed through magnetic resonance imaging (MRI) or computed tomography (CT) scan. Many patients did not recover from the reported adverse effects. Discuss the benefits and risks of epidural corticosteroid injections with patients. If the decision is made to proceed with epidural administration, counsel patients to seek medical attention immediately if they experience symptoms such as vision changes, tingling in arms or legs, any symptoms of stroke, or seizures.[57052] Injection use may result in dermal and/or subdermal changes forming depressions in the skin at the injection site. In order to minimize the incidence of subdermal and skin atrophy (dermal atrophy), care must be exercised not to exceed recommended doses in injections. Do not administer either form of parenteral methylprednisolone into the deltoid muscle (intramuscular administration in the deltoid muscle) as subcutaneous atrophy occurs with high frequency following such use. Furthermore, corticosteroid use via intramuscular administration for idiopathic/ immune thrombocytopenic purpura (ITP) is contraindicated, though intravenous and oral administration of methylprednisolone are utilized for this condition.[41361] [41362]

Systemic corticosteroid therapy, such as methylprednisolone, has been associated with left ventricular free-wall rupture in patients with recent myocardial infarction, and should therefore be used cautiously in these patients.[30015] [41361] [41362]

Use methylprednisolone with caution in patients with heart failure, hypertension, or renal disease as this can cause an exacerbation of their condition. Systemic corticosteroids can cause edema and weight gain.[30015] [41361] [41362]

Results from one multicenter, randomized, placebo-controlled study with methylprednisolone hemisuccinate, an IV corticosteroid, showed an increase in early (at 2 weeks) and late (at 6 months) mortality in patients with head trauma who were determined not to have other clear indications for corticosteroid treatment. High doses of systemic corticosteroids, including methylprednisolone, should not be used for the treatment of traumatic brain injury.[41361]

Chronic corticosteroid therapy, such as methylprednisolone, in pediatric patients may cause growth inhibition due to hypothalamic-pituitary-adrenal axis suppression and inhibition of bone growth. Corticosteroids should be titrated to the lowest effective dose. Because bone development is critical in pediatric patients, monitoring is warranted in patients receiving high-dose or chronic corticosteroid treatment. Potential adverse effects of chronic therapy should be weighed against the clinical benefits obtained and the availability of other treatment alternatives. Chronic systemic corticosteroid use can promote the development of osteopenia and osteoporosis in people of any age. Vertebral compression fractures, aseptic necrosis of femoral and humeral heads, and pathologic fractures of long bones, increased bone resorption, and protein catabolism can occur.[30015] [41361] [41362]

Use with caution in patients with diabetes mellitus. Systemic corticosteroids, such as methylprednisolone, may decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus. This may especially occur in patients predisposed to diabetes mellitus. When corticosteroid therapy is necessary in patients with diabetes mellitus, changes in insulin, oral antidiabetic agent dosage, and/or diet may be required.[30015] [41361] [41362]

Additional monitoring and/or periodic methylprednisolone dosage adjustments may been needed in patients with thyroid disease, as corticosteroid metabolic clearance is affected by thyroid function. Patients with hyperthyroidism have an increased rate of methylprednisolone elimination and may have a less than expected drug-effect; while those with hypothyroidism have decreased corticosteroid clearance and can have an exaggerated drug response.[30015] [41361] [41362]

Systemic corticosteroid use may be associated with neuro-psychiatric effects ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychosis. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. Inform patients or caregivers of the potential for mood and behavioral changes with methylprednisolone systemic treatment and encourage them to seek medical attention if psychiatric symptoms develop, especially if depressed mood (depression) or suicidal ideation is suspected.[30015] [41361] [41362]

An acute myopathy has been observed with the use of high doses of systemic corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.[30015] [41361] [41362]

Prolonged use of systemic corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure or glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infection due to bacteria, fungi or viruses.  The use of systemic corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.[30015] [41361] [41362]

Methylprednisolone should be used with caution in active or latent peptic ulcer disease, diverticulitis, fresh intestinal anastomoses, and non-specific ulcerative colitis, since these conditions may increase the risk of a GI perforation. Signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent..[30015] [41361] [41362]

Patients with severe hepatic disease, such as cirrhosis, can have an exaggerated response to systemic corticosteroids, such as methylprednisolone.[30015] [41361] [41362] Rarely, high doses of cyclically pulsed intravenous methylprednisolone (usually for the treatment of exacerbations of multiple sclerosis at doses of 1 gram/day) can induce a toxic form of acute hepatitis. The time to onset of this form of steroid-induced liver injury can be several weeks or longer. Resolution has been observed after discontinuation of treatment. However, serious liver injury can occur, sometimes resulting in acute liver failure and death. Discontinue intravenous methylprednisolone if toxic hepatitis occurs. Since recurrence has occurred after re-challenge, avoid use of high dose intravenous methylprednisolone in patients with a history of toxic hepatitis caused by methylprednisolone.[41361]

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, the response to such vaccines may be diminished. Indicated immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of corticosteroids.[30015] [41361] [41362] Corticosteroid therapy such as methylprednisolone usually does not contraindicate vaccination with live-virus vaccines when such therapy is of short-term (less than 2 weeks); low to moderate dose; long-term alternate day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or via topical administration (skin or eye), by aerosol, or by intra-articular, bursal or tendon injection. The immunosuppressive effects of steroid treatment differ, but many clinicians consider a dose equivalent to either 2 mg/kg/day or 20 mg/day of prednisone as sufficiently immunosuppressive to raise concern about the safety of immunization with live-virus vaccines. When cancer chemotherapy or immunosuppressive therapy is being considered (e.g., for patients with Hodgkin's disease or organ transplantation), vaccination should precede the initiation of chemotherapy or immunotherapy by 2 weeks. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy. In patients who have received high-dose, systemic corticosteroids for 2 weeks or more, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.[43236]

Tumor lysis syndrome (TLS) has been reported in patients with neoplastic disease, including hematological malignancies and solid tumors, following the use of systemic corticosteroids alone or in combination with other chemotherapeutic agents. Patients at high risk of TLS, such as patients with tumors that have a high proliferative rate, high tumor burden and high sensitivity to cytotoxic agents, should be monitored closely and appropriate precautions should be taken.[30015] [41362] [41361]

An increased incidence of scleroderma renal crisis has been observed with the use of corticosteroids, including methylprednisolone, in people with scleroderma.[30015] [41361] [41362]

Kaposi's sarcoma has been reported to occur in individuals during systemic corticosteroid therapy, such as methylprednisolone, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement of Kaposi's sarcoma.[30015] [41361] [41362]

Hypertrophic cardiomyopathy may develop after parenteral administration of methylprednisolone to premature neonates, therefore appropriate diagnostic evaluation and monitoring of cardiac function and structure should be performed.[41361] Several commercial formulations of methylprednisolone injection contain benzyl alcohol; formulations preserved with benzyl alcohol are contraindicated for use in premature neonates and should be used with caution in neonates. Administration of benzyl alcohol to neonates can result in 'gasping syndrome,' which is a potentially fatal condition characterized by metabolic acidosis and CNS, respiratory, circulatory, and renal dysfunction; it is also characterized by high concentrations of benzyl alcohol and its metabolites in the blood and urine. While the minimum amount of benzyl alcohol at which toxicity may occur is not known, 'gasping syndrome' has been associated with benzyl alcohol dosages greater than 99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic failure, renal failure, hypotension, bradycardia, and cardiovascular collapse. Rare cases of death, primarily in premature neonates, have been reported. Furthermore, an increased incidence of kernicterus, especially in small, premature neonates has been reported. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources. Premature neonates, neonates with a low birth weight, and patients who receive a high dose may be more likely to develop benzyl alcohol toxicity.[41361] [41362]

Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Complications, including cleft palate, stillbirth, and premature abortion, have been reported during animal studies. If methylprednisolone must be used during pregnancy, the potential risks should be discussed with the patient. Infants born to mothers who have taken substantial doses of corticosteroids during pregnancy should be monitored for signs of hypoadrenalism.[30015] [41361] [41362] Under certain circumstances, methylprednisolone may be considered for use in the pregnant patient (e.g., severe asthma exacerbation); poorly-controlled asthma and exacerbations generally present a greater risk to the mother and fetus than do neecessary asthma treatments.[64807] The American College of Obstetricians and Gynecologists (ACOG) include methylprednisolone as a last-line treatment option for nausea and vomiting of pregnancy in patients who have failed other therapies and suggest a limited duration of use for this purpose in responding patients.[66066]

Methylprednisolone use is generally considered compatible with breast-feeding. Amounts of methylprednisolone in breast milk are low, with a relative infant dose of 0.46% to 3.15%. No infant adverse effects have been reported with maternal methylprednisolone use, even with intravenous doses of up to 1 gram daily. At higher daily methylprednisolone doses, avoidance of breast-feeding during times of peak milk concentrations (usually until 3 to 4 hours following a dose) can help limit infant exposure. Medium to large doses of corticosteroids and intra-articular injections have been associated with a temporary decrease in milk supply.[70364] [70365] There are reports of breast-feeding in 3 infants who were breastfed from birth during maternal use of methylprednisolone (6 to 8 mg PO daily) with no reported adverse effects up to 3 months.[33727] [33728] In 1 of the reports, 2 babies had normal blood cell counts, no increase in infections, and above average growth rates.[33728]

According to the Beers Criteria, systemic corticosteroids are considered potentially inappropriate medications (PIMs) for use in geriatric patients with delirium or at high risk for delirium; avoid when possible in these patient populations due to the possibility of new-onset delirium or exacerbation of the current condition. Oral and parenteral corticosteroids may be required for conditions such as exacerbation of chronic obstructive pulmonary disease (COPD) but should be prescribed in the lowest effective dose and for the shortest possible duration.[63923]