Drug Interaction Report

MONITOR CLOSELY: Prolonged use of immunosuppressants, particularly high-dose corticosteroids, after administration of allogenic thymocyte-depleted thymus tissue implant, may increase the risk of damage to the implant. However, Graft Versus Host Disease (GVHD) may be caused by or exacerbated by allogenic thymocyte-depleted thymus tissue implant in patients with congenital athymia and require treatment with systemic immunosuppressive therapy. In addition, patients with congenital athymia are at an increased risk of autologous GVHD (aGVHD), which may also require systemic immunosuppressive therapy, including treatment with corticosteroids such as methylprednisolone and prednisolone.

MANAGEMENT: The manufacturer advises that prolonged use of immunosuppressive therapies, including high-dose corticosteroids, should be avoided in patients who have received an allogenic thymocyte-depleted thymus tissue implant. Some authorities consider the use of high-dose corticosteroids in the period immediately after implant to be contraindicated and generally advise against the use of pulse corticosteroids (such as methylprednisolone 30 to 40 mg/kg/day for 3 days) post-implant due to the potential for permanent damage to the implant. If immunosuppressive therapy is required post-implant, patients should be closely monitored for signs of damage to the implant as well as adverse effects from the concomitant immunosuppressant(s). The concomitant immunosuppressant(s) should be weaned as soon as clinically possible.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.