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]

Severe 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. Use of methylprednisolone is contraindicated for intrathecal administration.[41361] [41362] Do not give methylprednisolone acetate (e.g., Depo-Medrol) via intravenous administration.[41362] Do not administer any form of parenteral methylprednisolone into the deltoid muscle as subcutaneous atrophy occurs with high frequency following such use.[41361] [41362] Epidural administration of corticosteroids should be used with great caution. Rare, but serious neurologic events, including cortical blindness, stroke, spinal cord infarction, paralysis, seizures, nerve injury, brain edema, and death have been associated with epidural administration of injectable corticosteroids. These events have been reported with and without the use of fluoroscopy. Many cases were temporally associated with the corticosteroid injection; reactions occurred within minutes to 48 hours after injection. Some cases 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 the patient before treatment. If a decision is made to proceed with corticosteroid epidural administration, counsel patients to seek emergency medical attention if they experience symptoms after injection such as vision changes, tingling in the arms or legs, dizziness, severe headache, seizures, or sudden weakness or numbness of face, arm, or leg.[41361] [57053]

Corticosteroid therapy can mask the symptoms of infection, reactivate latent infection, exacerbate concurrent infection, and result in the development of secondary infection. Regardless of the dosage formulation, use of methylprednisolone is contraindicated in patients with systemic fungal infection, except when the acetate parenteral suspension (e.g., Depo-Medrol) is administered as an intra-articular injection for a localized joint condition [41362] or when the sodium succinate parenteral solution (e.g., Solu-Medrol) or oral formulations are used to control drug reactions.[41361] Further, use of any methylprednisolone formulation is not advised in cases of viral infection or bacterial infections that are not adequately controlled by antiinfective agents. The safety and efficacy of methylprednisolone sodium succinate in patients with sepsis syndrome and septic shock have not been established; study suggests that such use may increase the risk of mortality in patients with elevated serum creatinine levels and in those who develop secondary infections after methylprednisolone use.[41361] Do not administer parenteral methylprednisolone intra-articularly, intrabursally, or for intratendinous use for local effect in the presence of an acute infection [41361] [41362]; further, local administration of methylprednisolone acetate into a previously infected site is not usually recommended.[41362] Activation of latent disease or exacerbation of intercurrent infection due to pathogens such as Amoeba, Candida, Cryptococcus, Mycobacterium (mycobacterial infection), Nocardia, Pneumocystis, or Toxoplasma can occur in patients receiving systemic corticosteroids. Rule out infection with latent or active amebiasis before initiating methylprednisone therapy in patients who have spent time in the tropics or who have unexplained diarrhea. Use methylprednisone with caution in patients with known or suspected Strongyloides (threadworm) infestation as the immunosuppressive effects may lead to disseminated infection, severe enterocolitis, and sepsis. Cases of severe and disseminated strongyloidiasis have been reported following use of corticosteroids in combination with tocilizumab to treat patients with coronavirus disease 2019 (COVID-19). Before giving these drugs together to patients from strongyloidiasis endemic areas, consider administering ivermectin as prophylactic treatment.[65314] Reserve systemic corticosteroid therapy in active tuberculosis for patients with fulminating or disseminated disease and only in conjunction with appropriate antituberculosis therapy. Reactivation of tuberculosis may occur in patients with latent tuberculosis or tuberculin reactivity; close observation for disease reactivation is needed if methylprednisone is indicated in such patients. Furthermore, chemoprophylaxis is advised if prolonged methylprednisone therapy is needed. Advise patients receiving immunosuppressive doses of systemic corticosteroids to avoid exposure to persons with a viral infection (i.e., measles or varicella) because these diseases may be more serious or even fatal in immunosuppressed patients. Instruct patients to get immediate medical advice if exposure occurs.[30015] [41361] [41362]

Patients should be instructed to notify their physician immediately if signs of infection or injury occur, both during treatment or up to 12 months following cessation of therapy with methylprednisolone. Dosages should be adjusted, or glucocorticoid therapy reintroduced, if required. If surgery is needed, patients should advise the attending physician of the corticosteroid they have received within the last 12 months and the disease for which they were being treated. Identification cards that include the name of the patient's disease, the currently administered type and dose of corticosteroid, and the patient's physician should be carried with the patient at all times.

Corticosteroid therapy has been associated with left ventricular free-wall rupture in patients with recent myocardial infarction and methylprednisolone should therefore be used cautiously in these patients.

Corticosteroids cause edema, which can exacerbate congestive heart failure or hypertension. Methylprednisolone should be used with caution in these patients.

Corticosteroids should be used cautiously in patients with glaucoma or other visual disturbance. Corticosteroids are well known to cause cataracts and increased intraocular pressure and can exacerbate glaucoma during long-term administration. Patients receiving methylprednisolone chronically should be periodically assessed for cataract formation.

Methylprednisolone should be used with extreme caution in patients with psychosis, emotional instability, herpes infection (especially ocular herpes simplex infections), osteoporosis, diabetes mellitus, renal disease or seizure disorder because corticosteroids can exacerbate these conditions. Caution should also be used when treating patients with systemic sclerosis (scleroderma); an increased incidence of scleroderma renal crisis has been observed with the use of corticosteroids, including methylprednisolone.[30015] [41361] [41362]

Methylprednisolone should be used with caution in patients with myasthenia gravis who are being treated with anticholinesterase agents (see Interactions). Muscle weakness can be transiently increased during the initiation of glucocorticoid therapy in patients with myasthenia gravis, necessitating respiratory support.

Systemic corticosteroids should be used with caution in patients with active or latent peptic ulcer disease, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, since steroids may increase the risk of a gastrointestinal (GI) perforation. Signs of peritoneal irritation following GI perforation in patients receiving corticosteroids may be minimal or absent. Corticosteroids should not be used in patients where there is a possibility of impending GI perforation, abscess, or pyogenic infection. There is an enhanced effect due to decreased metabolism of corticosteroids in patients with severe hepatic disease with cirrhosis.[30015] [41361] [41362]

Glucocorticoids rarely can increase blood coagulability and cause intravascular thrombosis, thrombophlebitis, and thromboembolism. Therefore, methylprednisolone should be used with caution in patients with coagulopathy and/or thromboembolic disease. It is important to note that corticosteroid use via intramuscular administration for immune thrombocytopenic purpura (ITP) is contraindicated, though intravascular and oral administration of methylprednisolone are utilized for this condition.[41361] [41362]

There are no adequate or well controlled studies of the use of methylprednisolone in pregnant women. Complications, including cleft palate, stillbirth, and premature abortion, have been reported when corticosteroids were administered during pregnancy in animals. If these drugs must be used during pregnancy, the potential risks should be discussed with the patient. Babies born to women receiving large doses of corticosteroids during pregnancy should be monitored for signs of adrenal insufficiency, and appropriate therapy should be initiated, if necessary. Corticosteroids have been shown to impair fertility in male rats.[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 needed 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]

Corticosteroids distribute into breast milk, and the manufacturer states that because of the potential for serious adverse reactions in nursing babies, a decision should be made whether to discontinue nursing or to discontinue the drug.[41361] However, there have been reports of breast-feeding in 3 babies who were breast-fed 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 one of the reports, 2 babies had normal blood cell counts, no increase in infections, and above average growth rates.[33728] 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. While the American Academy of Pediatrics does not comment on the use of methylprednisolone during breast-feeding, it does consider other corticosteroids (prednisone and prednisolone) to be usually compatible with breast-feeding.[27500] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Pediatric-specific issues should be considered prior to treatment initiation with systemic corticosteroids, such as methylprednisolone. The potential for growth inhibition should be monitored during prolonged therapy in infants, children, and adolescents, and the potential for growth effects should be weighed against the clinical benefit obtained and the availability of other treatment alternatives. Administration of corticosteroids to pediatric patients should be limited to the least amount compatible with an effective therapeutic regimen.[41361] Pediatric patients may be more susceptible to developing systemic toxicity; adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of various corticosteroid formulations in young patients.[51792] [58998] Further, children receiving corticosteroids are immunosuppressed and are therefore more susceptible to infection. Normally innocuous infections can become fatal in children receiving systemic corticosteroids, so care should be taken to avoid exposure to patients with infectious diseases, particularly those with chicken pox or measles.[41361]

Glucocorticoids can produce or aggravate Cushing's syndrome, thus methylprednisolone should be avoided in patients with Cushing's disease.

Pharmacologic doses of methylprednisolone administered for prolonged periods may result in hypothalamic-pituitary-adrenal (HPA) suppression. Acute adrenal insufficiency and even death may occur following abrupt discontinuation. 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. Also, a non-HPA withdrawal syndrome may occur following abrupt discontinuation of corticosteroid therapy, and is apparently unrelated to adrenocortical insufficiency. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels (see Adverse Reactions).

All forms of methylprednisolone should be used with caution in newborns due to potential for drug-induced growth inhibition and immunosuppression. 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. Several commercial formulations of parenteral methylprednisolone are contraindicated in premature neonates and should be avoided in neonates because these products contain benzyl alcohol. 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 preterm infants, have been reported. Further, an increased incidence of kernicterus, especially in small, preterm infants 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 infants, infants with a low birth weight, and patients who receive a high dose may be more likely to develop toxicity.[30015] [41361] [41362]

True corticosteroid hypersensitivity reactions are rare. The use of methylprednisolone products in a patient who has previously experienced a hypersensitivity reaction to that product is contraindicated. While a hypersensitivity reaction could be to a specific salt of the corticosteroid (i.e., methylprednisolone sodium succinate), patients who have demonstrated a prior hypersensitivity reaction to methylprednisolone should receive any form of methylprednisolone with extreme caution. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids; there have been reports that a cross-sensitivity between hydrocortisone and methylprednisolone may exist.[27642] 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. Such patients should be carefully monitored during and following the administration of any corticosteroid.[27616]

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]

Use systemic corticosteroids with caution in the geriatric adult; the risks and benefits of therapy should be considered for any individual patient, particularly with chronic use. 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]

Patients receiving high-dose systemic corticosteroid therapy, such as methylprednisolone, for any period of time are at risk to develop immunosuppression; patients receiving moderate dosages of systemic corticosteroids for short periods or low doses for prolonged periods also may be at risk. When given in combination with other immunosuppressive agents, there is a risk of significant immunosuppression.[41361]

Corticosteroid therapy such as methylprednisolone usually does not contraindicate vaccination with live-virus vaccines when such therapy is of short-term (< 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. In general, patients with severe immunosuppression due to large doses of corticosteroids should not receive vaccination 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, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.

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]