Drug Interaction Report

MONITOR: Coadministration with sevelamer may reduce blood levels of oral cyclosporine, mycophenolate mofetil, and tacrolimus. The mechanism is reduction of absorption by sevelamer. Concomitant use of sevelamer with mycophenolate mofetil in adult and pediatric patients decreased the mean Cmax and AUC of mycophenolic acid (MPA) by 36% and 26%, respectively. Adverse effects, such as graft rejection in transplant patients, have not been reported. Data are lacking for an interaction with other phosphate binders.

MANAGEMENT: The immunosuppressant may be given at least 1 to 2 hours before or 2 to 3 hours after sevelamer administration to minimize the impact on absorption. It is recommended to closely monitor blood concentrations of the immunosuppressant during concomitant use and after discontinuation of sevelamer.

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

ADJUST DOSING INTERVAL: Sevelamer may decrease the oral bioavailability of concomitantly administered drugs. While clinical data are lacking for most drugs, the intestinal absorption of some may be impaired due to sevelamer's binding capabilities.

MANAGEMENT: As a precaution, drugs that can be adversely affected by alterations in blood levels should be administered 1 hour before or 3 hours after sevelamer.