Description
Methylprednisolone inhibits CYP3A4-mediated cyclosporine metabolism, raising cyclosporine levels; conversely, cyclosporine may increase methylprednisolone exposure — a bidirectional pharmacokinetic interaction.
Mechanism
High-dose methylprednisolone (pulse therapy) can inhibit CYP3A4, reducing cyclosporine clearance and raising trough levels; cyclosporine itself inhibits P-gp and CYP3A4, potentially increasing methylprednisolone exposure. The net direction of the interaction depends on relative doses.
Clinical Significance
Transplant cases document cyclosporine toxicity (nephrotoxicity, neurotoxicity) following methylprednisolone pulses for acute rejection; cyclosporine troughs may rise by 20–40%.
Management
Monitor cyclosporine trough levels during and after methylprednisolone pulse therapy; adjust cyclosporine dose as needed; monitor renal function closely.