Introduction
Methylprednisolone is a prednisolone derivative glucocorticoid with higher potency than prednisone. It was first described in the literature in the late 1950s.
Methylprednisolone was granted FDA approval on 24 October 1957. In the outbreak of COVID-19, low dose methylprednisolone-based therapy was successful in treating COVID-19-associated pneumonia in one patient with long-term immunosuppression. The efficacy of methylprednisolone in novel coronavirus pneumonia is being investigated further in clinical trials.
Uses
Methylprednisolone is a corticosteroid used to treat inflammation or immune reactions across a variety of organ systems, endocrine conditions, and neoplastic diseases.
Oral and intramuscular methylprednisolone are indicated for a number of endocrine, rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, gastrointestinal, nervous system, and other disorders. Intra-articular and soft tissue injections are indicated for short term treatment of acute gouty arthritis, acute and subactute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, and synovitis of osteoarthritis. Intralesional injections are indicated for alopecia areata, discoid lupus erythematosus, keloids, lichen planus, lichen simplex chronicus and psoriatic plaques, necrobiosis lipoidica diabeticorum, and localized hypertrophic infiltrated inflammatory lesions of granuloma annulare.
Associated Conditions
Pharmacodynamics
Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.
Mechanism of Action
The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.
Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.
Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.
Absorption
Oral methylprednisolone has 89.9% the bioavailability of oral methylprednisolone acetate, while rectal methylprednisolone has 14.2% the bioavailability. Intravitreal methylprednisolone has a Tmax of 2.5h. Approximately 1/10 of an oral or IV dose of methylprednisolone will reach the vitreous humor. Further data regarding the absorption of methylprednisolone are not readily available.
Volume of Distribution
The average volume of distribution of methylprednisolone is 1.38L/kg.
Protein Binding
Methylprednisolone is 76.8% protein bound in plasma and does not significantly bind to corticosteroid binding protein. Methylprednisolone is bound to human serum albumin in plasma.
Route of Elimination
Methylprednisolone and its metabolites have been collected in urine in humans. A study in dogs showed 25-31% elimination in urine and 44-52% elimination in feces.
Half Life
Methylprednisolone has a half life of 2.3h.
Clearance
The average plasma clearance of methylprednisolone is 336mL/h/kg.
Toxicity
The oral LD50 in rats is >4g/kg. The intraperitoneal LD50 in mice is 2292mg/kg and in rats is 100mg/kg.
Data regarding acute overdoses of glucocorticoids are rare. Chronic high doses of glucocorticoids can lead to the development of cataract, glaucoma, hypertension, water retention, hyperlipidemia, peptic ulcer, pancreatitis, myopathy, osteoporosis, mood changes, psychosis, dermal atrophy, allergy, acne, hypertrichosis, immune suppression, decreased resistance to infection, moon face, hyperglycemia, hypocalcemia, hypophosphatemia, metabolic acidosis, growth suppression, and secondary adrenal insufficiency. Treat acute overdoses with symptomatic and supportive therapy, while chronic overdoses will require temporarily reduced dosages.
Food Interactions
- Avoid alcohol.
- Take with food. Food reduces GI irritation.
Dosage
Although adverse effects associated with high dose short-term corticoid therapy are uncommon, peptic ulceration may occur. Prophylactic antacid therapy may be indicated.
In other indications, the initial dosage will vary from 10 to 40 mg of Methylprednisolone depending on the clinical problem being treated. The larger doses may be required for short-term management of severe, acute conditions. The initial dose usually should be given intravenously over a period of several minutes. Subsequent doses may be given intravenously or intramuscularly at intervals dictated by the patient’s response and clinical condition. Corticoid therapy is an adjunct to, and not a replacement for conventional therapy.
Dosage must be decreased or discontinued gradually when the drug has been administered for more than a few days. If a period of spontaneous remission occurs in a chronic condition, treatment should be discontinued. Routine laboratory studies, such as urinalysis, two-hour postprandial blood sugar, determination of blood pressure and body weight, and a chest X-ray should be made at regular intervals during prolonged therapy. Upper GI X-rays are desirable in patients with an ulcer history or significant dyspepsia.
In pediatric patients, the initial dose of Methylprednisolone may vary depending on the specific disease being treated. The initial dose is 0.11-1.6 mg/day in three or four divided doses. Dosage may be reduced for infants and children but should be governed more by the severity of the condition and response of the patient than by age or size but it should not be less than 0.5 mg per kg every 24 hours.
In the treatment of acute exacerbations of multiple sclerosis daily doses is 160 mg daily for 3 days. Methylprednisolone powder for injection/infusion should be given as an intravenous infusion over at least 30 minutes.
