Label Changes for:

Prograf (tacrolimus) Capsules, 0.5 mg, 1 mg, and 5 mgPrograf (tacrolimus) Injection, 5 mg/ml

September 2013

Changes have been made to the WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)  

  

September 2013

5 WARNINGS AND PRECAUTIONS

5.13 Use with CYP3A4 Inhibitors and Inducers
  • When coadministering Prograf with strong CYP3A4-inhibitors (e.g., telaprevir, boceprevir, ritonavir, ketoconazole, itraconazole, voriconazole, clarithromycin) and strong inducers (e.g., rifampin, rifabutin) adjustments in the dosing regimen of Prograf and subsequent monitoring of tacrolimus whole blood trough concentrations and tacrolimus-associated adverse reactions are recommended
5.14 QT Prolongation
  • Prograf may prolong the QT/QTc interval and may cause Torsade de Pointes. Avoid Prograf in patients with congenital long QT prolongation syndrome. In patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other medicinal products that lead to QT prolongation, and those with electrolyte disturbances such as hypokalemia, hypocalcemia, or hypomagnesemia, consider obtaining electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment.
  • When coadministering Prograf with other substrates and/or inhibitors of CYP3A4 that also have the potential to prolong the QT interval, a reduction in Prograf dose, frequent monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended. Use of Prograf with amiodarone has been reported to result in increased tacrolimus whole blood concentrations with or without concurrent QT prolongation [see Drug Interactions (7)].
5.18 Gastrointestinal Perforation
  • Gastrointestinal perforation has been reported in patients treated with tacrolimus; all reported cases were considered to be a complication of transplant surgery or accompanied by infection, diverticulum, or malignant neoplasm. As gastrointestinal perforation may be serious or lifethreatening, appropriate medical/surgical management should be instituted promptly [see Adverse Reactions (6.1)].

6 ADVERSE REACTIONS

  • Gastrointestinal Perforation [see Warnings and Precautions (5.18)]

7 DRUG INTERACTIONS

  • Dose adjustments may be needed along with frequent monitoring of tacrolimus whole blood trough concentrations when Prograf is administered with CYP3A inhibitors or inducers. In addition, patients should be monitored for adverse reactions including changes in renal function and QT prolongation [see Warnings and Precautions (5.7) and (5.14)].
      

July 2012

WARNINGS AND PRECAUTIONS

  • Use with CYP3A4 Inhibitors and Inducers Including Those That Prolong QT 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.

DRUG INTERACTIONS

Protease Inhibitors
  • ….Whole blood concentrations of tacrolimus are markedly increased when coadministered with telaprevir or with boceprevir.
Others
  • amiodarone

  

February 2012

ADVERSE REACTIONS

Postmarketing Adverse Reactions

Hemic/Lymphatic

  • Agranulocytosis
  • hemolytic anemia

     

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