Use of sirolimus (2 mg per day) with Tacrolimus in heart transplant patients in a U.S. trial was associated with increased risk of renal function impairment, wound healing complications, and insulin-dependent post-transplant diabetes mellitus, and is not recommended [see Clinical Studies (14.3)].

5.13 Use with CYP3A4 Inhibitors and Inducers Including Those That Prolong QT
Coadministration with strong CYP3A4-inhibitors (e.g., telaprevir, boceprevir, ritonavir, ketoconazole, itraconazole, voriconazole, clarithromycin) and strong inducers (e.g., rifampin, rifabutin) is not recommended without adjustments in the dosing regimen of Tacrolimus and subsequent close monitoring of Tacrolimus whole blood trough concentrations and Tacrolimus-associated adverse reactions [see Drug Interactions (7)].  

When coadministering Tacrolimus with other substrates and/or inhibitors of CYP3A4 that also have the potential to prolong the QT interval, a reduction in Tacrolimus dose, close monitoring of Tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended. Use of Tacrolimus with amiodarone has been reported to result in increased Tacrolimus whole blood concentrations with or without concurrent QT prolongation..

5.14 Myocardial Hypertrophy
Myocardial hypertrophy has been reported in infants, children, and adults, particularly those with high Tacrolimus trough concentrations, and is generally manifested by echocardiographically demonstrated concentric increases in left ventricular posterior wall and interventricular septum thickness. This condition appears reversible in most cases following dose reduction or discontinuance of therapy. In patients who develop renal failure or clinical manifestations of ventricular dysfunction while receiving Tacrolimus therapy, echocardiographic eva luation should be considered. If myocardial hypertrophy is diagnosed, dosage reduction or discontinuation of Tacrolimus should be considered [see Adverse Reactions (6.2)].

5.15 Immunizations
The use of live vaccines should be avoided during treatment with Tacrolimus; examples include (not limited to) the following: intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines.

5.16 Pure Red Cell Aplasia
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with Tacrolimus. A mechanism for Tacrolimus-induced PRCA has not been elucidated. All patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease, or concomitant medications associated with PRCA. If PRCA is diagnosed, discontinuation of Tacrolimus should be considered [see Adverse Reactions (6.2)].

Adverse Reactions
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:

•Lymphoma and Other Malignancies [see Box Warning, Warnings and Precautions (5.2)]
•Serious Infections [see Box Warning, Warnings and Precautions (5.3)]
•Polyoma Virus Infections [see Box Warning, Warnings and Precautions (5.4)]
•CMV Infections [see Box Warning, Warnings and Precautions (5.5)]
•New Onset Diabetes After Transplant [see Warnings and Precautions (5.6)]
•Nephrotoxicity [see Warnings and Precautions (5.7)]
•Neurotoxicity [see Warnings a