Methylprednisolone, sold under the brand name Medrol among others, is a synthetic glucocorticoid, primarily prescribed for its anti-inflammatory and immunosuppressive effects. It is either used at low doses for chronic illnesses or used at high doses during acute flares. Methylprednisolone and its derivatives can be administered orally or parenterally.
Regardless of the route of administration, methylprednisolone integrates systemically as exhibited by its effectiveness to quickly reduce inflammation during acute flares. It is associated with many adverse reactions that require tapering off the drug as soon as the disease is under control. Serious side effects include iatrogenic Cushing's syndrome, hypertension, osteoporosis, diabetes, infection, psychosis, and skin atrophy.
Chemically, methylprednisolone is a synthetic pregnane steroid hormone derived from hydrocortisone and prednisolone. It belongs to a class of synthetic glucocorticoids and more generally, corticosteroids. It acts as a mineralocorticoid and glucocorticoid receptor agonist. In comparison to other exogenous glucocorticoids, methylprednisolone has a higher affinity to glucocorticoid receptors than to mineralocorticoid receptors.
Glucocorticoid's name was derived after the discovery of their involvement in regulating carbohydrate metabolism. The cellular functions of glucocorticoids, such as methylprednisolone, are now understood to regulate homeostasis, metabolism, development, cognition, and inflammation. They play a critical role in adapting and responding to environmental, physical, and emotional stress.
Methylprednisolone was first synthesized and manufactured by The Upjohn Company (now Viatris) and approved for use by the Food and Drug Administration (FDA) in the United States in October 1957. In 2023, it was the 135th most commonly prescribed medication in the United States, with more than 4 million prescriptions. It is on the World Health Organization's List of Essential Medicines.
Medical uses The primary use of methylprednisolone is to suppress inflammatory and immune responses. Methylprednisolone achieves this primarily by regulating the number and function of leukocytes, cytokines, and chemokines. Its widespread inflammatory control is conducive in use across multiple disorders regardless of pathology. Methylprednisolone is commonly prescribed as short-term therapy for acute flares, as seen with acute gouty arthritis. It can be prescribed during on-going therapy in lower doses contingent upon monitorization of adverse effects. Dosage strength and formulation are optimized per medical use.
Asthma In 2001–2002, 11.4% of patients diagnosed with asthma and seen at an outpatient visit were prescribed oral corticosteroids as a long-term control therapy.National Center for Health Statistics. Health, United States, 2004 With Chartbook on Trends in the Health of Americans. Hyattsville, Maryland: 2004 https://www.cdc.gov/nchs/data/hus/hus04.pdf The National Asthma Education and Prevention Program (NAEPP) indicates systemic methylprednisolone in both short- and long-term therapies to quickly control and to suppress persistent asthma, respectively. For exacerbations that result in a visit to the emergency department (ED), oral methylprednisolone is preferred over intravenous administration, unless there are issues with adherence or vomiting. Oral methylprednisolone is less invasive and studies have shown equivalent efficacy to intravenous methylprednisolone. Dosage above 60–80 mg/day or 2 mg/kg/day is not recommended as it has not been shown to alter pulmonary function, rate of admission, or length of stay in the hospital compared to lower doses. Following ED discharge, it is advised to prescribe a five-day course of methylprednisolone to decrease the probability of relapse or withdrawal symptoms.
Rheumatic diseases Methylprednisolone is used to treat several rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methylprednisolone dosage and administration for these diseases is highly variable due to varied pathophysiology between the diseases and within patients diagnosed with a given disease. In lupus nephritis, a common manifestation of SLE, patients are often prescribed methylprednisolone concomitantly with immunosuppressants. Severe manifestations are often treated with cyclophosphamide or rituximab and three doses of methylprednisolone IV-pulse treatment (as recommended by ACR guidelines) before switching to oral prednisolone and azathioprine for maintenance.
Intra-articular corticosteroid injections (IACI) are a second-line therapy to relieve joint pain resulting from rheumatoid arthritis.Habib, G.S. Systemic effects of intra-articular corticosteroids. Clin. Rheumatol. 2009, 28, 749–756. It is most commonly injected into the joints of the knees and shoulders. Although the injection is local, studies have shown systemic absorption as evidenced by beneficial effects on distant joints. In an attempt to minimize HPA suppression, FDA guidelines have restricted IACIs to three per year, with a minimum of 30 days in between injections.
Primary or secondary adrenocortical insufficiency Methylprednisolone is not typically recommended for primary or secondary adrenocortical insufficiency compared to other corticosteroids which have a higher affinity for mineralocorticoid receptors and salt-retaining properties.
Labeled indications The labeled indications below are categorized by route of administration and then by medical discipline.
Oral methylprednisolone Allergy and immunology: angioneurotic edema, asthma, urticaria, seasonal or perennial allergic rhinitis, drug hypersensitivity reactions, and serum sickness. Dermatology: toxic epidermal necrolysis, atopic dermatitis, contact dermatitis, pemphigus, erythema multiforme, Stevens–Johnson syndrome, bullous dermatitis herpetiformis, severe seborrheic dermatitis, exfoliative dermatitis, mycosis fungoides, and severe psoriasis. Endocrinology: congenital adrenal hyperplasia, hypercalcemia associated with cancer, nonsuppurative thyroiditis, and primary or secondary adrenocortical insufficiency. Gastroenterology: inflammatory bowel disease and ulcerative colitis. Hematology: acquired (autoimmune) hemolytic anemia, idiopathic thrombocytopenic purpura, secondary thrombocytopenia, erythroblastopenia, leukemia, lymphoma and congenital (erythroid) hypoplastic anemia. Pulmonary: aspiration pneumonitis, chronic beryllium disease, eosinophilic pneumonia, symptomatic sarcoidosis, and pulmonary tuberculosis in conjunction with antituberculosis chemotherapy. Nephrology: nephrotic syndrome, idiopathic type or secondary to lupus nephritis. Neurology: multiple sclerosis. Ophthalmology: scleritis, retinal vasculitis, uveitis, choroiditis, iritis, iridocyclitis, keratitis, optic neuritis, allergic conjunctivitis, allergic corneal marginal ulcers, herpes zoster ophthalmicus, sympathetic ophthalmia, and chorioretinitis. Rheumatology: rheumatoid arthritis, rheumatic carditis, acute gouty arthritis, ankylosing spondylitis, dermatomyositis and polymyositis, psoriatic arthritis, systemic lupus erythematosus, acute and subacute bursitis, synovitis of osteoarthritis, post-traumatic osteoarthritis, and epicondylitis. Miscellaneous: trichinosis with neurologic or myocardial involvement.
Parenteral methylprednisolone Intra-articular or soft tissue injections: acute gouty arthritis, acute and subacute bursitis, acute tenosynovitis, epicondylitis, and synovitis of osteoarthritis. Intralesional injections: alopecia areata, discoid lupus erythematosus, keloids, granuloma annulare, lichen planus, lichen simplex chronicus, psoriatic plaques, necrobiosis lipoidica diabeticorum. Intramuscular injections are prescribed to treat many of the same conditions indicated for oral administration. Intramuscular injections are administered as an alternative to oral therapy.
Off-label indications Some of the off-label indications of methylprednisolone include acute spinal cord injury, acute respiratory distress syndrome, alcoholic hepatitis, hormonal resuscitation in cadaveric organ recovery, and chronic obstructive pulmonary disease.
Available forms
+Available Forms of methylprednisoloneActive IngredientBrand NameROAFormStrength1Inactive IngredientsmethylprednisoloneMedrolOraltablet2, 4, 8, 16, 32 mgcalcium stearate, cornstarch, lactose, mineral oil, sorbic acid, sucrose, and erythrosine sodium (2 mg only), FD&C yellow No. 6 (8 and 32 mg only)methylprednisoloneMedrolOraltablet4 mg; 21 pills (dose-pack)calcium stearate, cornstarch, lactose, sucrosemethylprednisolone acetateDepo-MedrolParenteral: intra-articular or soft tissue, intralesional or intramuscularsuspension20, 40, 80 mg/mlPolyethylene glycol 3350, Polysorbate 80, Monobasic sodium phosphate, Dibasic sodium phosphate USP, Benzyl alcohol2 added as a preservativemethylprednisolone acetate3Depo-MedrolParenteral: intra-articular or soft tissue, intralesional or intramuscularsuspension40 or 80 mg/ml (single dose vial)Polyethylene glycol 3350 Myristyl-gamma-picolinium chloridemethylprednisolone succinateSolu-MedrolParenteral: intravenous or intramuscularsolution, reconstituted500, 1000, 2000 mg/vial, 2000 mg with diluent (multi-dose vial)monobasic sodium phosphate anhydrous, dibasic sodium phosphate dried, and lactose hydrous. Bacteriostatic water added as diluent with Benzyl alcohol2 added as a preservativemethylprednisolone succinate3Solu-MedrolParenteral: intravenous or intramuscularsolution, reconstituted40, 125, 500, 1000 mg/vial (single dose vial)monobasic sodium phosphate anhydrous, dibasic sodium phosphate dried, and lactose hydrous. Footnotes:
1Signifies varying strengths of available forms. Is not indicative of frequency nor daily cumulative dose; varies per patient and condition.
2Benzyl alcohol should not be used on neonates
3Preservative free formulation
Contraindications Methylprednisolone should not be taken orally by people who have systemic fungal infections, except for Depo-Medrol when administered as an intra-articular injection for localized joint conditions. Methylprednisolone is contraindicated in those with known hypersensitivity to methylprednisolone or its components. Corticosteroids should be used with caution in patients with ulcerative colitis, heart disease or hypertension, peptic ulcer, renal insufficiency, osteoporosis, myasthenia gravis, glaucoma, and diabetes. Psychiatric manifestations may appear while taking methylprednisolone, ranging from euphoria, insomnia, personality changes, or depression. Caution is required for patients with predisposed psychoses, as psychotic tendencies may be exacerbated while taking corticosteroids.
Solu-Medrol 40 mg dosage contains lactose monohydrate produced from cow's milk; It should not be taken by anyone with known hypersensitivity to dairy products or its components. Severe medical events have been associated with epidural administration of Solu-Medrol and Depo-Medrol, including spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. Intramuscular injections should not be administered to those with idiopathic thrombocytopenic purpura. Formulations of Solu-Medrol and Depo-Medrol containing benzyl alcohol are contraindicated for use in premature infants. Exposure of neural tissue to excessive amounts of benzyl alcohol has been associated with toxicity and in rare events has resulted in death.
Adverse effects
Adverse reactions may overshadow the therapeutic effects of methylprednisolone.
Central nervous system