7.1 Mycophenolic Acid Products
With a given dose of mycophenolic acid (MPA) products, exposure to MPA is higher with Tacrolimus co-administration than with cyclosporine co-administration because cyclosporine interrupts the enterohepatic recirculation of MPA while Tacrolimus does not. Clinicians should be aware that there is also a potential for increased MPA exposure after crossover from cyclosporine to Tacrolimus in patients concomitantly receiving MPA-containing products.

7.2 Grapefruit Juice
Grapefruit juice inhibits CYP3A-enzymes resulting in increased Tacrolimus whole blood trough concentrations, and patients should avoid eating grapefruit or drinking grapefruit juice with Tacrolimus [see Dosage and Administration (2.5)].

7.3 Protease Inhibitors
Most protease inhibitors inhibit CYP3A enzymes and may increase Tacrolimus whole blood concentrations. It is recommended to avoid concomitant use of Tacrolimus with nelfinavir unless the benefits outweigh the risks [see Clinical Pharmacology (12.3)]. Whole blood concentrations of Tacrolimus are markedly increased when co-administered with telaprevir or with boceprevir [see Clinical Pharmacology (12.3)]. Monitoring of Tacrolimus whole blood concentrations and Tacrolimus-associated adverse reactions, and appropriate adjustments in the dosing regimen of Tacrolimus are recommended when Tacrolimus and protease inhibitors (e.g., ritonavir, telaprevir, boceprevir) are used concomitantly. .

7.4 Antifungal Agents
Frequent monitoring of whole blood concentrations and appropriate dosage adjustments of Tacrolimus are recommended when concomitant use of the following antifungal drugs with Tacrolimus is initiated or discontinued [see Clinical Pharmacology (12.3)].

Azoles: Voriconazole, posaconazole, itraconazole, ketoconazole, fluconazole and clotrimazole inhibit CYP3A metabolism of Tacrolimus and increase Tacrolimus whole blood concentrations. When initiating therapy with voriconazole or posaconazole in patients already receiving Tacrolimus, it is recommended that the Tacrolimus dose be initially reduced to one-third of the original dose and the subsequent Tacrolimus doses be adjusted based on the Tacrolimus whole blood concentrations.

Caspofungin is an inducer of CYP3A and decreases whole blood concentrations of Tacrolimus.

7.5 Calcium Channel Blockers
Verapamil, diltiazem, nifedipine, and nicardipine inhibit CYP3A metabolism of Tacrolimus and may increase Tacrolimus whole blood concentrations. Monitoring of whole blood concentrations and appropriate dosage adjustments of Tacrolimus are recommended when these calcium channel blocking drugs and Tacrolimus are used concomitantly.

7.6 Antibacterials
Erythromycin, clarithromycin, troleandomycin and chloramphenicol inhibit CYP3A metabolism of Tacrolimus and may increase Tacrolimus whole blood concentrations. Monitoring of blood concentrations and appropriate dosage adjustments of Tacrolimus are recommended when these drugs and Tacrolimus are used concomitantly.

7.7 Antimycobacterials
Rifampin [see Clinical Pharmacology (12.3)] and rifabutin are inducers of CYP3A enzymes and may decrease Tacrolimus whole blood concentrations. Monitoring of whole blood concentrations and appropriate dosage adjustments of Tacrolimus are recommended when these antimycobact