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.

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.