Description: Methylprednisolone and its derivatives, methylprednisolone sodium succinate and methylprednisolone acetate, are synthetic glucocorticoids used orally or parenterally as antiinflammatory or immunosuppressive agents. These drugs have very little mineralocorticoid activity and are therefore not used to manage adrenal insufficiency unless a more potent mineralocorticoid is administered concomitantly. Methylprednisolone was originally approved by the FDA in 1957. Mechanism of Action: Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately, protein synthesis to achieve the steroid's intended action. Such actions can include: inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. Some of the net effects include reduction in edema or scar tissue as well as a general suppression in immune response. The degree of clinical effect is normally related to the dose administered. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Likewise, the numerous adverse effects related to corticosteroid use are usually related to the dose administered and the duration of therapy. Pharmacokinetics: Methylprednisolone is administered orally, while methylprednisolone sodium succinate may be administered by IM or IV injection or by IV infusion. Methylprednisolone acetate may be administered by IM, intra-articular, intralesional, or soft tissue injection. Methylprednisolone is rapidly absorbed following an oral dose. Peak effects following oral and IV administration occur within 1�2 hours. The onset and duration of action of methylprednisolone suspensions are dependent on whether the drug is administered by intra-articular or IM injection, and on the extent of the local blood supply. Absorption of methylprednisolone from an intra-articular injection site can be very slow, continuing over about 7 days. Methylprednisolone is quickly distributed into the kidneys, intestines, skin, liver, and muscle. Corticosteroids distribute into breast milk and cross the placenta. Methylprednisolone is metabolized by the liver to inactive metabolites. These inactive metabolites, as well as a small portion of unchanged drug, are excreted in the urine. The biological half-life of methylprednisolone is 18�36 hours. Indications...Dosage Equivalent Glucocorticoid dosages. These are general approximations and may not apply to all diseases or routes of administration. Equivalent glucocorticoid dosages: Cortisone--25 mg Hydrocortisone--20 mg Prednisolone--5 mg Prednisone--5 mg Methylprednisolone--4 mg Triamcinolone--4 mg Dexamethasone--0.75 mg Betamethasone--0.6 mg For the palliative management of leukemia and lymphoma in adults and acute leukemias of childhood including acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hodgkin's disease, non-Hodgkin's lymphoma (NHL), or multiple myeloma�: NOTE: For many conditions, the dosing of corticosteroids is highly variable; the following general dosing recommendations apply. Oral dosage: Adults: 4�48 mg/day PO, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Subsequent doses are determined by patient response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intramuscular or Intravenous dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. For the treatment of inflammatory bowel disease during critical periods of ulcerative colitis and regional enteritis (Crohn's disease): NOTE: For many conditions, the dosing of corticosteroids is highly variable; the following general dosing recommendations apply. Oral dosage: Adults: 4�48 mg/day PO, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Subsequent doses are determined by patient response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intramuscular or Intravenous dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. Rectal dosage for ulcerative colitis (methylprednisolone acetate): Adults: 40 mg PR 3�7 times a week for two or more weeks. Children: 0.5�1 mg/kg or 15�30 mg/m2 PR every 1�2 days for two or more weeks. For the management of symptomatic sarcoidosis: NOTE: Treatment with corticosteroids is usually indicated only if hypercalcemia is present or if there is a decline in the function of a vital organ (lungs, kidneys, eyes, heart, or CNS). The dosing of corticosteroids is highly variable; the following general dosing recommendations apply. Oral dosage: Adults: Initially, 24�32 mg/day PO. Alternatively, 40�48 mg PO every other day has also been used. Taper after several weeks to the lowest effective maintenance dose (often 8�12 mg PO every other day). Intravenous dosage (methylprednisolone sodium succinate): Adults: A dose of 30 mg/kg IV once a week for 6 weeks, with or without oral maintenance corticosteroid therapy, has been used. Therapy produced immediate improvement in all patients, however, 66% relapsed 1 year later. One patient without oral maintenance corticosteroids and 3 patients with oral maintenance corticosteroids showed persistent improvement.[1786] For the treatment of hypercalcemia associated with certain types of cancer, including myeloma, lymphoma, leukemia, or breast carcinoma: Oral dosage: Adults: 32�80 mg/day PO is usually effective for hypercalcemia due to hematologic cancers. 12�24 mg/day PO may be sufficient for other tumors (e.g., breast carcinoma). The dosage listed is based on a recommended prednisone dose converted to an equivalent methylprednisolone dose. For the treatment of trichinosis with neurologic or myocardial involvement: Oral or intravenous dosage: Adults: The optimal dosage has not been established; critically-ill patients may require high doses (e.g., 48 mg/day PO or IV) for 2 or more weeks. The dosage listed is based on a recommended prednisone dose converted to an equivalent methylprednisolone dose. For the treatment of non-neoplastic hematologic disorders including idiopathic thrombocytopenic purpura (ITP), secondary thrombocytopenia in adults, acquired (autoimmune) hemolytic anemia, erythroblastopenia (RBC anemia), and congenital hypoplastic anemia: NOTE: For many conditions, the dosing of corticosteroids is highly variable; the following general dosing recommendations apply. Oral dosage: Adults: 4�48 mg/day PO, depending on disease treated, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. Intravenous or Intramuscular dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. NOTE: IM administration is contraindicated in patients with ITP. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. For the treatment of myasthenia gravis in patients who are poorly controlled with cholinesterase inhibitor therapy: Oral dosage: Adults and adolescents: Initially, 12�20 mg/day PO. Increased, as needed, by 4 mg PO every 2�3 days until there is marked clinical improvement or to a maximum of 40 mg/day PO. Dose is usually continued for 1�3 months and then is gradually tapered to an alternate-day dosage. Some clinicians use initial dosages of 48�64 mg/day PO with gradual tapering. Although higher initial dosages may provide more rapid benefit, early exacerbations of myasthenic weakness may be more common than with lower initial dosages. The methylprednisolone dosage listed is based on a recommended prednisone dose converted to an equivalent methylprednisolone dose. For the treatment of adrenocortical function abnormalities, such as adrenocortical insufficiency, congenital adrenal hyperplasia, chronic primary (Addison's disease) or secondary adrenocortical insufficiency, or adrenogenital syndrome: NOTE: Hydrocortisone and cortisone are the preferred drugs; methylprednisolone has little to no mineralocorticoid properties. For acute conditions, parenteral therapy is recommended. Dosing is highly variable; the following are general dosages. Oral dosage: Adults: 4�48 mg/day PO, depending on disease treated, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Subsequent IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intramuscular, intravenous or IV infusion dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. For the treatment of allergic disorders including anaphylaxis or anaphylactoid reactions, angioedema, acute noninfectious laryngeal edema, drug hypersensitivity reactions, serum sickness, severe perennial or seasonal allergic rhinitis, or urticaria: �For oral treatment of mild conditions: Oral dosage: Adults: 4�48 mg/day PO, depending on disease treated, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. �for the injectable treatment of severe conditions like anaphylaxis, angioedema, or urticarial transfusion-related reactions: Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Subsequent IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intramuscular, intravenous or IV infusion dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. For drug-induced angioedema failing to respond to epinephrine or H1-blockers, short courses of 40�120 mg/day IV can be given for the late phase of an acute reaction.[570] Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. For the adjunctive treatment of tuberculosis: �for the adjunctive treatment of fulminating or disseminated pulmonary tuberculosis (with appropriate antituberculosis therapy): Oral dosage: Adults: 4�48 mg/day PO, depending on disease treated, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Frequency of dosing varies with condition and response. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intramuscular, intravenous or IV infusion dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. �for the adjunctive treatment of tuberculous meningitis when used concurrently with appropriate antituberculosis therapy: Oral dosage: Adults: Initially, 48�64 mg/day PO; experts recommend corticosteroid use in stage 2 (confusion or the presence of focal neurological defects) or stage 3 (stuporous or dense paraplegia or hemiplegia) TB meningitis. Gradually taper after 1�2 weeks and discontinue by 4�6 weeks, guided by the patient's symptoms. For the treatment of respiratory conditions including asthma, airway-obstructing hemangioma� in infants, aspiration pneumonitis, berylliosis, chronic obstructive pulmonary disease (COPD), laryngotracheobronchitis (croup), Loeffler's syndrome, or noncardiogenic pulmonary edema�, or for bronchospasm prophylaxis: �for chronic oral management of patients with asthma and other respiratory conditions: Oral dosage: Adults: 4�48 mg/day PO, depending on disease treated, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, given in divided doses every 6�12 hours. �for the treatment of an acute mild asthma exacerbation on an outpatient basis: Oral dosage: Adults: The National Asthma Education and Prevention Expert Panel recommends 40�60 mg PO as 1�2 divided doses for 3�10 days.[1515] Children: The National Asthma Education and Prevention Expert Panel recommends 1�2 mg/kg/day (max: 60 mg/day) PO as 1�2 divided doses for 3�10 days.[1515] �for the treatment of a moderate-severe asthma exacerbation in the emergency department or the hospital: Oral or intravenous dosage: Adults: The National Asthma Education and Prevention Expert Panel recommends 120�180 mg/day PO or IV in 3�4 divided doses for 48 hours, then 60�80 mg/day PO or IV until the peak expiratory flow (PEF) reaches 70% of predicted or personal best.[1515] Children: The National Asthma Education and Prevention Expert Panel recommends 1 mg/kg PO or IV every 6 hours for 48 hours, then 1�2 mg/kg/day (max: 60 mg/day) PO or IV in 2 divided doses until peak expiratory flow (PEF) reaches 70% of predicted or personal best.[1515] �for the parenteral management of non-asthmatic respiratory conditions when oral dosing not feasible or severity or compromised airway warrants: Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Frequency of dosing varies with the condition being treated and patient response. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intramuscular, intravenous or IV infusion dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. For the treatment of corticosteroid-responsive dermatologic disorders (e.g., alopecia areata, atopic dermatitis, bullous dermatitis herpetiformis, contact dermatitis including Rhus dermatitis due to poison ivy, poison oak, poison sumac, discoid lupus erythematosus, eczema, exfoliative dermatitis, insect bites or stings, granuloma annulare, keloids, lichen striatus, lichen planus, lichen simplex, mycosis fungoides, necrobiosis lipoidica diabeticorum, pemphigus, pityriasis rosea, polymorphous light eruption, pruritus, psoriasis, seborrheic dermatitis, or xerosis): �for the treatment of mild-moderate corticosteroid responsive dermatoses: Oral dosage: Adults: 4�48 mg/day PO, depending on disease treated, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. �for the treatment of severe inflammatory dermatoses, like exfoliative dermatitis, severe psoriasis, erythema multiforme or Stevens-Johnson syndrome: Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Subsequent doses may be given determined by patient response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intramuscular, intravenous or IV infusion dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. For adjunctive therapy in the treatment of rheumatic disorders including acute gouty arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis (JRA), post-traumatic osteoarthritis, pseudogout�, psoriatic arthritis, or rheumatoid arthritis, or for the treatment of acute episodes or exacerbation of nonrheumatic inflammatory conditions including acute and subacute bursitis, epicondylitis, and acute non-specific tenosynovitis: NOTE: For many conditions, the dosing of corticosteroids is highly variable; the following general dosing recommendations apply. Oral dosage: Adults: 4�48 mg/day PO, depending on disease treated, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Subsequent doses may be given determined by patient response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intra-articular injection or Intra-lesional dosage (methylprednisolone acetate): Adults: 10�80 mg at the appropriate site, depending upon degree of inflammation and size and location of affected area. Repeat doses are not usually required for 1�5 weeks. Dosage ranges for specific joints: Large joints: 20�80 mg; Medium joints: 10�40 mg; Small joints: 4�10 mg. Suggested intralesional dosage range is 20�60 mg. Intramuscular, intravenous or IV infusion dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. For adjunctive therapy in the treatment of carpal tunnel syndrome�: NOTE: The definitive treatment for median-nerve entrapment is surgery. Corticosteroids are temporary measures; patients who have intermittent pain and paresthesias without any fixed motor-sensory deficits may respond to conservative therapy. Local injection (methylprednisolone acetate, e.g., Depo-Medrol�): Adults: 40�80 mg as a single injection adjacent to the carpal tunnel. Reassess at 6�8 weeks. To avoid median-nerve injury, use specialized administration techniques. Use of >= 2 or 3 repeat injections is not advised; local tendon damage may occur. For the treatment of selected cases of acute rheumatic carditis, systemic dermatomyositis (polymyositis), systemic lupus erythematosus (SLE), temporal arteritis�, mixed connective tissue disease�, polyarteritis nodosa�, relapsing polychondritis�, polymalgia rheumatica�, or vasculitis�: NOTE: For many conditions, the dosing of corticosteroids is highly variable; the following general dosing recommendations apply. �for routine treatment: Oral dosage: Adults: 4�48 mg/day PO, depending on disease treated, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Frequency of dosing varies with the condition and response. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intramuscular, intravenous or IV infusion dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. �for the treatment of systemic lupus erythematosus (SLE) in patients with severe, life-threatening disease, including diffuse proliferative glomerulonephritis (i.e., lupus nephritis�), cerebritis, or hemolytic disease: Intravenous dosage (methylprednisolone sodium succinate): Adults: A pulse regimen of 500�1000 mg IV once daily for 3�5 days is given to induce remission, followed by high-dose oral therapy (usually prednisone) that is rapidly tapered to maintenance therapy. In one study, IV methylprednisolone was compared with IV cyclophosphamide to prevent decline in renal function in patients with lupus nephritis.[50] Single monthly doses of methylprednisolone for 6 months were equivalent to single monthly doses of IV cyclophosphamide for 6 months. However, the benefit of either drug was not sustained, as patients who continued to receive quarterly doses IV cyclophosphamide for 2 more years demonstrated significantly less decline in renal function than either 6 month therapy group. The methylprednisolone dose in this study was 1 g/m2 IV infused over 30 minutes once daily for 3 consecutive days, followed by monthly injections of the same dose.[50] Children: 30 mg/kg IV infused over 30 minutes every other day for 6 doses, followed by long-term oral prednisone/prednisolone. For the treatment of the acute respiratory distress syndrome (ARDS): Intravenous and oral dosage: Adults: Corticosteroid use in ARDS is controversial. If there are no signs of improvement 7�14 days after ARDS onset, 1.6�3.2 mg/kg/day IV in divided doses for 7�14 days has been recommended.[564] Alternatively; a tapered dosage (2 mg/kg/day on days 1�14; 1 mg/kg/day on days 15�21; 0.5 mg/kg/day on days 22�28; 0.25 mg/kg/day on days 29�30; 0.125 mg/kg/day on days 31�32) is used. Initiate with the IV route, given in 4 divided doses; PO doses are administered as a single daily dose.[1701] For the treatment of acute exacerbations of multiple sclerosis: Oral dosage, intramuscular dosage (methylprednisolone acetate, methylprednisolone sodium succinate), or intravenous dosage (methylprednisolone sodium succinate): Adults: The manufacturer recommends 200 mg PO once daily for 7 days, followed by 80 mg PO every other day for 1 month. A dosage of 160 mg PO, IV or IM daily for one week, followed by 64 mg PO, IV or IM every other day for one month has also been used. Barnes et al. compared the efficacy of oral versus IV methylprednisolone for treating acute relapses of MS in adults. Thirty-eight patients were allocated to methylprednisolone 1 g IV once daily for 3 days; 42 patients were allocated to 48 mg PO once daily for 7 days, then 24 mg PO once daily for 7 days, and then to 12 mg PO once daily for 7 days. No differences were in seen in recovery between the 2 groups, however, limited recovery was noted in both groups. The authors concluded that the 2 routes were equally efficacious,[1550] however an editorialist (ACP Journal Club) remained unconvinced from this study that oral therapy was acceptable for this condition. For adjunctive therapy in Pneumocystis carinii pneumonia� in AIDS patients: Intravenous dosage (methylprednisolone sodium succinate): Adults: One well-controlled trial utilized 40 mg IV every 6 hours for 7 days.[241] The NIH-UC Expert Panel recommends 30 mg IV twice daily for 5 days, followed by 30 mg IV once daily for 5 days, and then 15 mg IV once daily for 11 days. Children: Safe dosage has not been established. For the treatment of acute spinal cord trauma�: Intravenous infusion dosage (methylprednisolone sodium succinate): Adults and children: 30 mg/kg IV given over 15 minutes, followed 45 minutes later by 5.4 mg/kg/hour IV infusion given for 23 hours. Although not widely employed, the continuous infusion has been repeated for an additional 23 hours in selected patients. For the treatment of nonsuppurative thyroiditis: Oral dosage: Adults: Glucocorticoids are reserved for severe cases. Although prednisone is commonly used, a methylprednisolone dosage of 16�32 mg/day PO has similar potency. For the treatment of acute kidney transplant rejection: Intravenous dosage (methylprednisolone sodium succinate): Adults and children: 250�1000 mg IV given once daily or on alternate days for 3�5 doses. For the treatment of acute graft-versus-host disease: Intravenous (methylprednisolone sodium succinate): Adults and children: 2�2.5 mg/kg/day IV, tapered slowly over 2�3 weeks. Initial doses of 10 mg/kg/day IV have also been used; although there is no definitive data that higher doses are more effective than lower doses. For GVHD limited to the skin, an initial dose of 1 mg/kg/day IV may be used. One study indicated that a cumulative methylprednisolone dose of 2000 mg/m2 (or roughly 50 mg/kg) is required for complete resolution of acute graft-versus-host disease in most patients.[1713] Intramuscular dosage (methylprednisolone acetate): Adults and children: 2�2.5 mg/kg/day IM, tapered slowly over 2�3 weeks. For the systemic treatment of ophthalmic disorders including allergic conjunctivitis, allergic marginal corneal ulcer, anterior segment inflammation, chorioretinitis, endophthalmitis�, Graves' ophthalmopathy, herpes zoster ophthalmicus, iritis, keratitis, postoperative ocular inflammation, optic neuritis, diffuse posterior uveitis, or vernal keratoconjunctivitis: NOTE: For many conditions, the dosing of corticosteroids is highly variable; the following general dosing recommendations apply. Oral dosage: Adults: 4�48 mg/day PO, depending on disease treated, administered in 4 divided doses. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day PO, in divided doses every 6�12 hours. Intramuscular dosage (methylprednisolone acetate): Adults: 10�120 mg IM. Subsequent doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM, in divided doses every 6�12 hours. Intramuscular or Intravenous dosage (methylprednisolone sodium succinate): Adults: Initially, 10�40 mg IV infused over several minutes. Subsequent IV/IM doses are determined by response and condition. Children: 0.5�1.7 mg/kg/day or 5�25 mg/m2/day IM/IV, in divided doses every 6�12 hours. Maximum Dosage Limits: Dosage must be individualized and is highly variable depending on the nature and severity of the disease, route of treatment, and on patient response. Patients with hepatic impairment: Systemic dosage may need adjustment depending on the degree of hepatic insufficiency, but quantitative recommendations are not available. Patients with renal impairment: Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. �non-FDA-approved indication Administration NOTE: Dosage must be individualized and is very variable depending on the nature and severity of the disease, and on the patients response. If therapy is continued for more than a few days, withdrawal must be gradual. Oral Administration �Administer methylprednisolone with meals to minimize indigestion or GI irritation. If given once daily or every other day, administer in the morning to coincide with the body's normal cortisol secretion. �For "Dose-Packs": Follow the administration and dose titration schedule as indicated on the package. Parenteral Administration �Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Direct intravenous injection (methylprednisolone sodium succinate): �Reconstitute with provided diluent or add 2 ml of bacteriostatic water (with benzyl alcohol) for injection. �May be administered undiluted. �Administer directly into a vein over 3�15 minutes. Doses >= 2 mg/kg or 250 mg should be given by intermittent infusion (see below), unless the potential benefits of direct IV injection outweigh the potential risks (e.g., life-threatening shock). Intermittent intravenous infusion (methylprednisolone sodium succinate): �Dilute in D5W, NS, or D5NS injection. Haze may form upon dilution. �Infuse over 15�60 minutes. Large doses (e.g., >= 500 mg) should be administered over at least 30�60 minutes. Intramuscular injection (methylprednisolone acetate or sodium succinate): �Shake suspension well prior to withdrawing into the syringe. �Inject deeply into a well develop muscle. Aspirate prior to injection to avoid injection into a blood vessel. Rotate sites of injection. Intra-articular injection (methylprednisolone acetate): �Using sterile technique, attach a 20�24 gauge needle to an empty syringe and insert the needle into the synovial cavity. Withdraw a few drops of synovial fluid to confirm that the needle is in the joint. With the needle still in place, exchange the aspirating syringe with the syringe containing methylprednisolone and inject the drug into the joint. Intralesional injection (methylprednisolone acetate): �Using a tuberculin syringe with a 25-gauge, �-inch needle, inject methylprednisolone intradermally (not subcutaneously). Contraindications Certain dosage forms of methylprednisolone injection should not be given by the intravenous route. Do not give methylprednisolone acetate (e.g. Depo-Medrol�) via intravenous administration. The manufacturers state that methylprednisolone is contraindicated in patients with systemic fungal infection; however, many clinicians believe that corticosteroids can be administered to patients with any type of known infection as long as appropriate antimicrobial therapy is administered simultaneously. Corticosteroid therapy can mask the symptoms of infection and should not be used in cases of viral infection or bacterial infections that are not adequately controlled by antiinfective agents. Secondary infections are common during corticosteroid therapy. 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 and, if exposed to these diseases, to seek medical advice immediately. 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. 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 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 can exacerbate glaucoma during long-term administration. Patients receiving corticosteroids chronically should be periodically assessed for cataract formation. Corticosteroids should be used with extreme caution in patients with psychosis, emotional instability, herpes infection (especially ocular herpes simplex infections), renal disease, osteoporosis, diabetes mellitus, or seizure disorder because corticosteroids can exacerbate these conditions. Patients with hypothyroidism can have an exaggerated response to corticosteroids, so any steroid should be used with caution in these patients. Glucocorticoids 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. Corticosteroids should be used with caution in patients with GI disease, diverticulitis, intestinal anastomosis (because of the possibility of perforation), or hepatic disease causing hypoalbuminemia such as cirrhosis. While used for the short-term treatment of acute exacerbations of chronic inflammatory bowel disease such as ulcerative colitis and Crohn's disease, corticosteroids should not be used in patients where there is a possibility of impending GI perforation, abscess, or pyogenic infection. Some patients may require long-term corticosteroid therapy to suppress disease activity, but generally this practice is not recommended. Corticosteroids should not be used in patients with peptic ulcer disease except under life-threatening circumstances. Glucocorticoids rarely can increase blood coagulability and cause intravascular thrombosis, thrombophlebitis, and thromboembolism. Therefore, corticosteroids should be used with caution in patients with coagulopathy and/or thromboembolic disease. Increased dosages of rapid-acting corticosteroids may be necessary for patients undergoing physiologic stress such as major surgery, acute infection, or blood loss. The corticosteroid should be administered before, during, and after the stressful situation. Complications, including cleft palate, stillbirth, and premature abortion, have been reported when corticosteroids were administered during pregnancy. 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. Methylprednisolone is classified as pregnancy category C. Corticosteroids distribute into breast milk, and the manufacturer states that women receiving pharmacological dosages of corticosteroids should avoid breast-feeding. Prolonged therapy with corticosteroids should be avoided in children because these drugs can retard bone growth. 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. Because glucocorticoids can produce or aggravate Cushing's syndrome, glucocorticoids should be avoided in patients with Cushing's disease. Pharmacologic doses of corticosteroids 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). Some oral preparations of methylprednisolone contain tartrazine dye and should be used with caution in patients with a known tartrazine dye hypersensitivity. Patients allergic to aspirin are often at risk. Corticosteroid therapy 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. Several commercial formulations of methylprednisolone are contraindicated in neonatal prematurity or other patients with benzyl alcohol hypersensitivity 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. Topical methylprednisolone should be used with extreme caution in patients with poor circulation due to the risk of skin ulceration. Because corticosteroids can inhibit wound healing, methylprednisolone should not be used in areas of skin abrasion. nteractions Hepatic microsomal enzyme inducers, including barbiturates, phenytoin, rifabutin, and rifampin, can increase the metabolism of glucocorticoids. Rifabutin and rifampin are particularly potent enzyme inducers. Dosages of methylprednisolone may require adjustment if these agents are initiated or withdrawn during corticosteroid therapy. Troleandomycin signficantly decreases the clearance of methylprednisolone however, similar changes were not observed with prednisolone. Clarithromycin or erythromycin also decrease the clearance of methylprednisolone. The clinical implications of these pharmacokinetic interactions are uncertain, but some studies have used the interaction to dose-reduce methylprednisolone in acutely asthmatic patients without compromising steroid efficacy. The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents. Estrogens can increase the concentration of transcortin, thus reducing the amount of unbound cortisone. In addition, estrogens have been shown to decrease the clearance of prednisolone. Therefore, the effects of corticosteroids may be altered by the concurrent administration of estrogen, requiring the adjustment of corticosteroid dosages if estrogen is added or withdrawn during therapy. The risk of GI ulceration from nonsteroidal antiinflammatory drugs (NSAIDs) can be increased with corticosteroid therapy. Aspirin, ASA should be used with caution in patients with hypoprothrombinemia who are also receiving corticosteroids. Serum salicylate levels can increase when corticosteroid therapy is discontinued, possibly due to a decrease in corticosteroid-induced metabolism of salicylates. This can rarely precipitate salicylate toxicity. Patients receiving these drugs concomitantly should be observed closely for evidence of adverse effects. The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including thiazide diuretics, furosemide, ethacrynic acid, and amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly. Glucocorticoids interact with cholinesterase inhibitors, including ambenonium, neostigmine, and pyridostigmine, causing severe muscle weakness in patients with myasthenia gravis who receive these drugs concomitantly. Glucocorticoids are used therapeutically, however, in the treatment of some patients with myasthenia gravis. Killed or inactivated vaccines and toxoids do not represent a danger to immunocompromised persons and generally should be administered as recommended for healthy persons. The immune response of immunocompromised persons to vaccines is not as good as healthy persons; higher doses or more frequent boosters may be required, although the immune response still may be suboptimal. Live-virus vaccines should not be given to immunocompromised individuals due to the potentiation of virus replication and adverse reactions to the virus. Those undergoing high-dose corticosteroid therapy should not be exposed to others who have recently received the oral poliovirus vaccine (OPV). Measles-mumps-rubella (MMR) vaccination is not contraindicated for the close contacts, including health care professionals, of immunocompromised patients. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. When exposed to a vaccine-preventable disease such as measles, severely immunocompromised children should be considered susceptible regardless of their vaccination history. Corticosteroid therapy rarely can increase blood coagulability. Patients receiving heparin or warfarin can experience loss of clinical effect. In addition, corticosteroids have been associated with gastrointestinal bleeding. Thus, corticosteroids should be used cautiously in patients receiving anticoagulants. Systemic corticosteroids increase blood glucose levels; a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Blood lactate concentrations and the lactate to pyruvate ratio increased when metformin was coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with an increased risk of lactic acidosis, so patients on metformin concurrently with systemic steroids should be monitored closely. Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions. Patients receiving cardiac glycosides and corticosteroids concomitantly are at an increased risk of developing arrhythmias or digitalis toxicity due to corticosteroid-induced hypokalemia. Corticosteroid-induced hypokalemia could also enhance the proarrhythmic effects of dofetilide. Hypokalemia also potentiates neuromuscular blockade associated with nondepolarizing neuromuscular blockers. Corticosteroids should be monitored closely when used with neuromuscular blockers. Corticosteriods administered prior to or concomitantly with porfimer photodynamic therapy may decrease the efficacy of the treatment. The risk of cardiac toxicity with isoproterenol in asthma patients appears to be increased with the coadministration of corticosteroids or methylxanthines. Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05-2.7 ug/kg/min have caused clinical deterioration, myocardial infarction (necrosis), congestive heart failure and death. High dose (i.e., 2 or 3 doses of 500�1000 mg administered over 24�72 hours) IV methylprednisolone may cause an increase in the INR of patients who are stabilized on warfarin. In one study, the mean INR in 10 patients increased from 2.75 to 8.04 following a methylprednisolone infusion. The mechanism of the interaction is unclear; however, it appears prudent to monitor the INR of patients on warfarin if parenteral methylprednisolone is co-administered. Mifepristone, RU-486 exhibits antiglucocorticoid activity that may antagonize the corticosteroids. In rats, the activity of dexamethasone was inhibited by oral mifepristone doses of 10�25 mg/kg. A mifepristone dose of 4.5 mg/kg in humans resulted in compensatory increases in ACTH and cortisol. Mifepristone is contraindicated in patients on long-term corticosteroid therapy. Increased tacrolimus levels, which may lead to nephrotoxicity, may be noted with concurrent methylprednisolone therapy. Verapamil and diltiazem may decrease the metabolism of methylprednisolone via inhibition of the CYP3A4 isoenzyme, with the potential for increased corticosteroid effects. Oral coadministration of diltiazem and methylprednisolone has been shown to increase the AUC of methylprednisolone by about 2.6-fold and increase the half-life from 1.6 to 3.1 hours. While food does not normally interfere with methylprednisolone, grapefruit juice may enhance steroid effects if taken with oral methylprednisolone. Grapefruit juice contains a furano-coumarin compound that inhibits CYP3A4 in enterocytes; decreased methylprednisolone metabolism is the probable mechanism. Methylprednisolone peak concentrations and AUC increased by 30% and 75%, respectively, and the half-life of methylprednisolone was prolonged in one study of the interaction. The clinical significance of the interaction is uncertain. Patients should be advised to not significantly alter their grapefruit juice ingestion. Adverse Reactions NOTE: Prolonged administration of physiologic replacement dosages of glucocorticoids usually does not cause adverse effects. The severity of the adverse effects associated with prolonged administration of pharmacological dosages of corticosteroids increases with duration and frequency of therapy. Short-term administration of large doses typically does not cause adverse effects, but long-term administration can lead to adrenocortical atrophy and generalized protein depletion. Glucocorticoids are responsible for protein metabolism, and prolonged therapy can result in various musculoskeletal manifestations, including: myopathy (myalgia, muscle wasting, muscle weakness), 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: 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.[1441] Postmenopausal women, in particular, should be monitored for signs of osteoporosis during corticosteroid 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. Sinus bradycardia has occurred during or after IV administration of large doses of methylprednisolone sodium succinate. Sinus tachycardia has also been reported rarely. Corticosteroid therapy can mask the symptoms of infection and should be avoided during an acute viral or bacterial infection. 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. Corticosteroids are divided into two classes: mineralocorticoids and glucocorticoids. 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 edema and hypertension. Mineralocorticoid properties can cause fluid retention; electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia); edema; and hypertension. Prolonged administration of glucocorticoids also can result in edema and hypertension. In a review of 93 studies of corticosteroid use, hypertension was found to develop 4 times as often in steroid recipients compared to control groups.[938] Congestive heart failure can occur in susceptible patients. 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 glucocorticoids 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 fungal and viral infections of the eye can be exacerbated by corticosteroid therapy. Prolonged corticosteroid therapy can adversely affect the endocrine system, resulting in hypercorticism (Cushing's syndrome), menstrual irregularity including amenorrhea or dysmenorrhea, hyperglycemia, and aggravation of diabetes mellitus in susceptible patients. In a recently-published review of 93 studies of corticosteroid use, the development of diabetes mellitus was determined to occur 4 times more frequently in steroid recipients compared to control groups.[938] Insulin or oral hypoglycemic dosages may require adjustment. Adverse GI effects associated with long-term corticosteroid administration include nausea/vomiting and anorexia with subsequent weight loss. Appetite stimulation with weight gain, diarrhea, constipation, abdominal pain, esophageal ulceration, gastritis, 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 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.[938] Adverse neurologic effects have been reported during prolonged corticosteroid administration and include headache, insomnia, vertigo, restlessness, ischemic peripheral neuropathy, seizures, and EEG changes. Mental disturbances, including depression, anxiety, euphoria, personality changes, and psychosis, have also been reported; emotional lability and psychotic problems can be exacerbated by corticosteroid therapy. Various adverse dermatologic effects reported during corticosteroid therapy include skin atrophy, acne vulgaris, diaphoresis, impaired wound healing, facial erythema, striae, petechiae, hirsutism, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, and/or angioedema. Paresthesias (burning or tingling) in the perineal area may occur following IV injection of corticosteroids. Parenteral corticosteroid therapy has also produced skin hypopigmentation, skin hyperpigmentation, scarring, and other injection site reactions (e.g., induration, delayed pain or soreness, subcutaneous and cutaneous atrophy, and sterile abscesses). Pharmacologic doses of corticosteroids 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. Hypercholesterolemia, atherosclerosis, fat embolism, thrombosis, thromboembolism, and phlebitis, specifically, thrombophlebitis have been associated with corticosteroid therapy. Thrombocytopenia has occurred in several patients receiving prolonged, high-dose corticosteroid therapy. Palpitations, glossitis, stomatitis, urinary incontinence, and urinary urgency have been rarely reported. Corticosteroids 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. |
Medrol�, A-methaPred�, Depo-Medrol�, Solu-Medrol�, Methylprednisolone by Duramed | Cortimed� | Depo Predate� | Depoject� | Depopred� | Duro Cort� | Key Drol� | Med Dep� | Medralone� | Meth-Pred� | Methacort� | Methylcotolone� | Predacorten� | Pri-Methylate� | Sano Drol� Reference 1713. Hings IM, Filipovich AH, Miller WJ et al. Prednisone therapy for acute graft-versus-host disease: short- versus long-term treatment. Transplantation 1993;56:577�80. 241. Gagnon S, Boota AM, Fischl MA et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. N Engl J Med 1990;323:1444�50. 1550. Barnes D, Hughes RA, Morris RW et al. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet 1997;349:902�6. 1701. Meduri GU, Headley AS, Golden E et al. Effect of prolonged methylprednisolone therapy in unresolving ARDS. JAMA 1998;280:159�65. 564. Kollef MH, Schuster DP. The acute respiratory distress syndrome. N Engl J Med 1995;332:27�37. 50. Boumpas DT, Austin HA III, Vaughn EM et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992;340:741�5. 570. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. Ann Intern Med 1992;117:234�42. 1515. National Asthma Education and Prevention Program Expert Panel 2. Expert panel report 2: guidelines for the diagnosis and management of asthma. Bethesda (MD): National Institutes of Health. National Heart, Lung, and Blood Institute; 1997 July. NIH Publication No. 97�4051. 938. Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med 1994;236:619�32. 1441. Reid IR. Preventing glucocorticoid-induced osteoporosis. N Engl J Med 1997;337:420�1. |