New Safety Information regarding the co-administration of Videx and Viread, and either Sustiva or Viramune - Bristol-Myers Squibb Canada and Gilead Sciences, Inc.

Date: 2005-07-18

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Health Canada Endorsed Important Safety Information on the co-administration of Videx & Viread, and either Sustiva or Viramune

Bristol-Myers Squibb Canada

June 9, 2005

Subject: New safety information regarding the co-administration of Videx and Viread, and either Sustiva or Viramune

Dear Health Care Professional,

Bristol-Myers Squibb Canada & Gilead Sciences, Inc. are writing to inform you of important new clinical data regarding the co-administration of Videx EC (didanosine delayed-release capsules enteric-coated beadlets [ddI EC]), Viread (tenofovir disoproxil fumarate [TDF]), and either Sustiva (efavirenz [EFV]) or Viramune (nevirapine [NVP]).

Co-administering tenofovir DF and didanosine should be undertaken with caution, and patients should be carefully monitored for efficacy and for didanosine-related adverse events. Didanosine should be discontinued in patients who develop didanosine-related adverse events.

• Reports from recent, investigator-sponsored trials have indicated a potential for a high rate of virological failure and emergence of resistance associated with the co-administration of didanosine and tenofovir DF with a non-nucleoside reverse transcriptase inhibitor (NNRTI) in antiretroviral treatment-naive HIV-infected adults with high baseline viral loads and low CD4 cell counts^1-3.
  
  
• Such early virologic failure appears to be limited to the specific combination of didanosine and tenofovir DF with either efavirenz or nevirapine as there are data from large scale trials supporting the efficacy of tenofovir DF and efavirenz-based regimens as well as didanosine and efavirenz-based regimens in treatment-naive HIV patients^4-7.
  
  
• Pharmacokinetic studies have shown that co-administration of didanosine and tenofovir DF results in 40-60% increase in systemic exposure to didanosine. Increases in didanosine concentration of this magnitude could potentiate didanosine-associated adverse events, including pancreatitis, lactic acidosis and neuropathy. The Product Monographs for Videx EC and Viread have been revised to include a recommendation to reduce the dose of Videx EC when co-administered with Viread and to carefully monitor patients for efficacy and didanosine-related adverse events. The recommended dose of didanosine EC is 250 mg for HIV-infected adults with body weight ≥60 kg and creatinine clearance ≥60 mL/min when co-administered with 300 mg tenofovir DF. For patients <60 kg, and creatinine clearance ≥60 mL/min, a reduced dose of 200 mg didanosine EC is recommended. Data are not available to recommend a dose adjustment of the buffered tablet formulation of didanosine (Videx).

The identification, characterization, and management of marketed health product-related adverse reactions are dependent on the active participation of health care professionals in adverse reaction reporting programmes. Any occurrences of a serious and/or unexpected adverse reaction in patients receiving Videx and Viread, and either Sustiva or Viramune should be reported to Bristol-Myers Squibb Canada and Gilead Sciences, Inc. or Health Canada at the following addresses:

original signed by

A.Tom Koutsavlis, MD, MSc, CSPQ, FRCPC
Director
Medical Affairs

original signed by

Jay Toole, MD, Ph.D.
Senior Vice President
Clinical Research