c) Lansoprazole (CYP2C19, CYP3A4 substrate) may potentially inhibit CYP3A4-mediated metabolism of tacrolimus and thereby substantially increase tacrolimus whole blood concentrations, especially in transplant patients who are intermediate or poor CYP2C19 metabolizers, as compared to those patients who are efficient CYP2C19 metabolizers.

a Drugs That May Decrease Tacrolimus Blood Concentrations

Anticonvulsants  Antimicrobials 
carbamazepine rifabutin 
phenobarbital caspofungin 
phenytoin rifampin
Herbal Preparations     Other Drugs 
St. John’s Wort sirolimus

a) This table is not all inclusive.

St. John’s Wort (Hypericum perforatum) induces CYP3A4 and P-glycoprotein. Since tacrolimus is a substrate for CYP3A4, there is the potential that the use of St. John’s Wort in patients receiving tacrolimus could result in reduced tacrolimus levels.

In a single-dose crossover study in healthy volunteers, co-administration of tacrolimus and magnesium-aluminum-hydroxide resulted in a 21% increase in the mean tacrolimus AUC and a 10% decrease in the mean tacrolimus Cmax relative to tacrolimus administration alone.

In a study of 6 normal volunteers, a significant decrease in tacrolimus oral bioavailability (14±6% vs. 7±3%) was observed with concomitant rifampin administration (600 mg). In addition, there was a significant increase in tacrolimus clearance (0.036±0.008 L/hr/kg vs. 0.053±0.010 L/hr/kg) with concomitant rifampin administration.

Interaction studies with drugs used in HIV therapy have not been conducted. However, care should be exercised when drugs that are nephrotoxic (e.g., ganciclovir) or that are metabolized by CYP3A (e.g., nelfinavir, ritonavir) are administered concomitantly with tacrolimus. Based on a clinical study of 5 liver transplant recipients, co-administration of tacrolimus with nelfinavir increased blood concentrations of tacrolimus significantly and, as a result, a reduction in the tacrolimus dose by an average of 16-fold was needed to maintain mean trough tacrolimus blood concentrations of 9.7 ng/mL. Thus, frequent monitoring of tacrolimus blood concentrations and appropriate dosage adjustments are essential when nelfinavir is used concomitantly. Tacrolimus may affect the pharmacokinetics of other drugs (e.g., phenytoin) and increase their concentration. Grapefruit juice affects CYP3A-mediated metabolism and should be avoided (see DOSAGE AND ADMINISTRATION ).

Following co-administration of tacrolimus and sirolimus (2 or 5 mg/day) in stable renal transplant patients, mean tacrolimus AUC0 to 12 and Cmin decreased approximately by 30% relative to tacrolimus alone. Mean tacrolimus AUC0 to 12 and Cmin following co-administration of 1 mg/day of sirolimus decreased approximately 3% and 11%, respectively. The safety and efficacy of tacrolimus used in combination with sirolimus for the prevention of graft rejection has not been established and is not recommended.

Other Drug Interactions
Immunosuppressants may affect vaccination. Therefore, during treatment with tacrolimus, vaccination may be less effective. The use of live vaccines should be avoided; live vaccines may include, but are not limited to measles, mumps, rube