Drug interactions between Gengraf and prednisone

cyclosporine ↔ prednisone

Applies to:Gengraf (cyclosporine) and prednisone

MONITOR: The coadministration of cyclosporine with a corticosteroid may result in altered (usually elevated) plasma concentrations of one or both drugs. Cyclosporine and corticosteroids undergo metabolism primarily by CYP450 3A4, thus competitive inhibition of metabolic clearance may occur during concomitant use. Plasma prednisolone concentrations have been reported to increase during coadministration with cyclosporine in transplant patients, resulting in symptoms of hypercorticism. Conversely, trough plasma levels of cyclosporine have been shown to increase following the addition of methylprednisolone in a group of patients treated for transplant rejection, some of whom required a reduction in cyclosporine dosage. There have also been isolated reports of seizures in patients receiving cyclosporine with high-dose methylprednisolone, although a causal relationship has not been established. Clinical data are not available for other corticosteroids. While all corticosteroids are believed to be substrates of CYP450 3A4 and, therefore, may be competitive inhibitors of cyclosporine metabolism, dexamethasone and prednisolone have also been reported to induce this isoenzyme, thus they may reduce levels of cyclosporine.

MANAGEMENT: Caution is advised during concomitant therapy with cyclosporine and corticosteroids or adrenocorticotropic agents (which increase endogenous corticosteroids). Pharmacologic responses and/or plasma drug levels should be monitored more closely whenever one or the other agent is added to or withdrawn from therapy in patients stabilized on their existing therapeutic regimen, and the dosage(s) adjusted as necessary. During concomitant therapy, patients should be observed for symptoms of hypercorticism (e.g., acne, bruising easily, moon face, edema, hirsutism, buffalo hump, skin striae) and cyclosporine toxicity (e.g., renal dysfunction, hypertension, convulsions, tremors).