indication

Adjunctive therapy for short-term administration in rheumatoid arthritis.

pharmacology

Methylprednisolone and its derivatives, methylprednisolone sodium succinate and methylprednisolone acetate, are synthetic glucocorticoids used as antiinflammatory or immunosuppressive agents.

mechanism of action

Unbound glucocorticoids cross cell membranes and bind with high affinity to specific cytoplasmic receptors, modifying transcription and protein synthesis. By this mechanism, glucocorticoids can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.

toxicity

LD₅₀=2000 mg/kg (orally in rat)

biotransformation

Hepatic

absorption

Oral bioavailability 80-99%

half life

1-3 hours

drug interactions

Acetylsalicylic acid: The corticosteroid, methylprednisolone, may decrease the effect of the salicylate, acetylsalicylic acid.

Aprepitant: Increases the effect and toxicity of methylprednisolone

Clarithromycin: The macrolide, clarithromycin, may increase the effect of corticosteroid, methylprednisolone.

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Methylprednisolone. Consider methylprednisolone dose titration and/or adjustments in patients receiving strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors) and monitor for increased steroid related adverse effects.

Erythromycin: The macrolide, erythromycin, may increase the effect of corticosteroid, methylprednisolone.

Fosphenytoin: The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, methylprednisolone.

Itraconazole: The imidazole, itraconazole, may increase the effect and toxicity of the corticosteroid, methylprednisolone.

Ketoconazole: The imidazole, ketoconazole, may increase the effect and toxicity of the corticosteroid, methylprednisolone.

Midodrine: Increased arterial pressure

Phenobarbital: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, methylprednisolone.

Phenytoin: The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, methylprednisolone.

Primidone: The barbiturate, primidone, may decrease the effect of the corticosteroid, methylprednisolone.

Pyridostigmine: The corticosteroid, methylprednisolone, may decrease the effect of the anticholinesterase, pyridostigmine.

Quinupristin: This combination presents an increased risk of toxicity

Rifampin: The enzyme inducer, rifampin, may decrease the effect of the corticosteroid, methylprednisolone.

Tacrine: Tacrine and Methylprednisolone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.

Tacrolimus: Methylprednisone may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Methylprednisone therapy is initiated, discontinued or altered.

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Vecuronium: Vecuronium may increase the adverse neuromuscular effects of systemic corticosteroids, such as Methylprednisolone. Monitor for increased muscle weakness and signs of polyneuropathies and myopathy.