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Label Changes for:

Nizoral (ketoconazole) Tablets

July 2013

Changes have been made to the BOXED WARNING, CONTRAINDICATIONS and WARNINGS sections of the safety label.

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

 

July 2013

BOXED WARNING

NIZORAL Tablets should be used only when other effective antifungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential risks.

Hepatotoxicity
  • Serious hepatotoxicity, including cases with a fatal outcome or requiring liver transplantation has occurred with the use of oral ketoconazole. Some patients had no obvious risk factors for liver disease. Patients receiving this drug should be informed by the physician of the risk and should be closely monitored.
QT Prolongation and Drug Interactions Leading to QT Prolongation
  • Co-administration of the following drugs with ketoconazole is contraindicated: dofetilide, quinidine, pimozide, cisapride. Ketoconazole can cause elevated plasma concentrations of these drugs and may prolong QT intervals, sometimes resulting in life-threatening ventricular dysrhythmias such as torsades de pointes.

CONTRAINDICATIONS

Liver Disease
  • The use of NIZORAL Tablets is contraindicated in patients with acute or chronic liver disease.
  • Section: Addition of a new subsection on liver disease and updated information on drug interactions.

WARNINGS

Hepatotoxicity
  • Serious hepatotoxicity, including cases with a fatal outcome or requiring liver transplantation, has occurred with the use of oral ketoconazole. Some patients had no obvious risk factors for liver disease. Serious hepatotoxicity was reported both by patients receiving high doses for short treatment durations and by patients receiving low doses for long durations….
QT Prolongation and Drug Interactions Leading to QT Prolongation
  • Ketoconazole can prolong the QT interval. Co-administration of the following drugs with ketoconazole is contraindicated: dofetilide, quinidine, pimozide, and cisapride.
  • Ketoconazole can cause elevated plasma concentrations of these drugs which may prolong the QT interval, sometimes resulting in life-threatening ventricular dysrhythmias such as torsades de pointes.
Adrenal Insufficiency
  • NIZORAL Tablets decrease adrenal corticosteroid secretion at doses of 400 mg and higher. This effect is not shared with other azoles. The recommended dose of 200 mg - 400 mg daily should not be exceeded.
  • Adrenal function should be monitored in patients with adrenal insufficiency or with borderline adrenal function and in patients under prolonged periods of stress (major surgery, intensive care, etc.).
Adverse Reactions Associated with Unapproved Uses
  • Ketoconazole has been used in high doses for the treatment of advanced prostate cancer and for Cushing’s syndrome when other treatment options have failed. The safety and effectiveness of ketoconazole have not been established in these settings and the use of ketoconazole for these indications is not approved by FDA.
  • In a clinical trial involving 350 patients with metastatic prostatic cancer, eleven deaths were reported within two weeks of starting treatment with high doses of ketoconazole tablets (1200 mg/day). It is not possible to ascertain from the information available whether death was related to ketoconazole therapy or adrenal insufficiency in these patients with serious underlying disease.
Hypersensitivity
  • Anaphylaxis has been reported after the first dose. Several cases of hypersensitivity reactions including urticaria have also been reported.
Enhanced Sedation
  • Co-administration of NIZORAL Tablets with oral midazolam, oral triazolam or alprazolam has resulted in elevated plasma concentrations of these drugs. This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents. Concomitant administration of NIZORAL Tablets with oral triazolam, oral midazolam, or alprazolam is contraindicated.)
Myopathy
  • Co-administration of CYP3A4 metabolized HMG-CoA reductase inhibitors such as simvastatin, and lovastatin is contraindicated with NIZORAL Tablets.
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