Increased dosages may be required to achieve desired effect of methylprednisolone.Cytochrome P450 (CYP) 3A4 inhibitors
Troleandomycin, ketoconazole, and Clarithromycin inhibit metabolism; and may decrease rate of elimination and increase half-life of methylprednisolone. Dosages should be decreased accordingly to avoid side effects. Another CYP 3A4 inhibitor, grapefruit juice, prolongs half-life of oral methylprednisolone.Oral contraceptives
Oral contraceptives inhibit oxidative processes, as highlighted by its ability to decrease methylprednisolone clearance.P-glycoprotein inhibitors
Methylprednisolone is shown to be a substrate of P-glycoprotein; its inhibition is thought to increase methylprednisone absorption and distribution. No clinical relevance has been linked.Ciclosporin, tacrolimus, sirolimus (Rapamycin)
Methylprednisolone and cyclosporin inhibit metabolism and therefore increase the likelihood of experiencing side effects associated with either of the individual drugs. In addition to known individual side effects, convulsions have been reported.Cox1 inhibitors
Methylprednisolone may increase rate of elimination with chronic high dose aspirin. Patients are susceptible to increased salicylate serum levels or salicylate toxicity upon termination of methylprednisolone. Excessive caution should be taken when prescribing methylprednisolone and aspirin to patients with hypoprothrombinemia.Anticoagulants

Anticoagulants exhibit variable interactions; monitoring coagulation indices is recommended to achieve the desired effect. Physical properties
Oral methylprednisolone (Medrol) and its derivatives are a white, odorless crystalline powder. Its solubility ranges from practically insoluble in water, very slightly soluble in ether, sightly soluble in acetone and chloroform to sparingly soluble in alcohol, dioxane and methanol. Methylprednisolone acetate suspension (Depo-Medrol) is a 6-methyl derivative of prednisolone that melts at 215 degrees Celsius with some decomposition. Methylprednisolone sodium succinate (Solu-Medrol) is the sodium succinate ester of methylprednisolone.
Methylprednisolone is also on the World Health Organizations List of Essential Medicines for its effects against lymphoid leukemia. Pharmacodynamics
Methylprednisolone is a synthetic glucocorticoid (GCs) that exhibits pleiotropic effects on a variety of physiological mechanisms. However, they have been prescribed extensively for their effects on inflammation and immunity. The effects of synthetic glucocorticoids, such as methylprednisolone, is dependent on its association with intracellular glucocorticoid receptors (GRs), and to a lesser extent, mineralocorticoid receptors (MRs). GRs are widely distributed in contrast to MRs that show a restricted tissue distribution. By this mechanism, the ligand-bound receptor translocate to the nucleus and modulate gene expression. Signal transduction
In the absence of endogenous or synthetic GCs, monomeric GRs are located in the cytoplasm and form multiprotein complexes with heat shock proteins (HSPs), immunophilins, and other chaperones such as src, and p23. The GR acts in a ligand-dependent manner, with the complex holding the GR in an inactive form with high specificity for the ligand. When methylprednisolone from the plasma or interstitial fluid diffuses passively across the cell membrane, it binds to the GR inducing a conformational change and GC-GR dimerization. It was previously thought that this conformational change was necessary to dissociate the multiprotein complex to allow the ligand bound receptor to translocate to the nucleus. However, recent studies have indicated that chaperones play a role in nuclear import. The now active methylprednisolone-GR complex can either transduce non-genomic changes in the cytoplasm or translocate to the nucleus and regulate transcriptional activity of target genes by direct, tethering or composite mechanisms.