Contraindications
Tacrolimus is contraindicated in patients with a hypersensitivity to Tacrolimus. Tacrolimus injection is contraindicated in patients with a hypersensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil). Hypersensitivity symptoms reported include dyspnea, rash, pruritus, and acute respiratory distress syndrome [see Adverse Reactions (6)].

Warnings and Precautions

5.1 Management of Immunosuppression
Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should use Tacrolimus. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physicians responsible for maintenance therapy should have complete information requisite for the follow up of the patient [see Box Warning].

5.2 Lymphoma and Other Malignancies
Patients receiving immunosuppressants, including Tacrolimus, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Box Warning]. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent.

As usual for patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.

Post transplant lymphoproliferative disorder (PTLD) has been reported in immunosuppressed organ transplant recipients. The majority of PTLD events appear related to Epstein Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children.

5.3 Serious Infections
Patients receiving immunosuppressants, including Tacrolimus, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections [see Box Warning and Warnings and Precautions (5.4, 5.5)]. These infections may lead to serious, including fatal, outcomes. Because of the danger of oversuppression of the immune system which can increase susceptibility to infection, combination immunosuppressant therapy should be used with caution.

5.4 Polyoma Virus Infections
Patients receiving immunosuppressants, including Tacrolimus, are at increased risk for opportunistic infections, including polyoma virus infections. Polyoma virus infections in transplant patients may have serious, and sometimes fatal, outcomes. These include polyoma virus-associated nephropathy (PVAN), mostly due to BK virus infection, and JC virus-associated progressive multifocal leukoencephalopathy (PML) which have been observed in patients receiving Tacrolimus [see Adverse Reactions (6.2)].

PVAN is associated with serious outcomes, including deteriorating renal function and kidney graft loss [see Adverse Reactions (6.2)]. Patient monitoring may help detect patients at risk for PVAN.

Cases of PML have been reported in patients treated with Tacrolimus.  PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies and ataxia. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients repo