Drug Interaction Report

MONITOR CLOSELY: Coadministration of macrolide immunosuppressants with other nephrotoxic agents may increase the risk and/or severity of renal impairment due to additive adverse effects on the kidney. No formal interaction studies have been performed. However, clinical experience in coadministration with cyclosporine indicates increased renal toxicity as evidenced by increased serum creatinine and decreased glomerular filtration rate. An interaction with ibuprofen resulting in acute renal failure was suspected in two liver transplant patients who had been stabilized on tacrolimus.

MANAGEMENT: Caution is advised when macrolide immunosuppressants is used in patients who have recently received or are receiving treatment with other potentially nephrotoxic drugs (e.g., aminoglycosides; polypeptide, glycopeptide, and polymyxin antibiotics; amphotericin B; adefovir; cidofovir; tenofovir; foscarnet; cisplatin; cyclosporine; deferasirox; gallium nitrate; lithium; mesalamine; intravenous bisphosphonates; intravenous pentamidine; high intravenous dosages of methotrexate; high dosages and/or chronic use of nonsteroidal anti-inflammatory agents). Renal function should be closely monitored both during and after discontinuation of therapy. Patients should be advised to seek medical attention if they experience symptoms that may indicate nephrotoxicity such as decreased urine output, sudden weight gain, fluid retention, edema, or shortness of breath.

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.