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Revised Package Insert for Atazanavir

The insert includes new information on administering the drug with acid-reducing therapies and on appropriate dosing in patients with renal failure.

In December 2007, the package insert for atazanavir was revised to include updated information on administering the drug concurrently with acid-reducing therapies. In addition, specific guidelines are now included for drug dosing in patients with renal failure.

Acid-Reducing Therapies
For treatment-naive patients who are initiating atazanavir and require proton-pump inhibitors (PPIs) or histamine-2 (H₂)-receptor antagonists:

• The PPI dose should not exceed the dose-equivalent of 20-mg omeprazole and must be taken approximately 12 hours before atazanavir (300 mg) and ritonavir (100 mg).
  
• The H₂-receptor–antagonist dose should not exceed the dose-equivalent of twice-daily 40-mg famotidine. Atazanavir (300 mg) and ritonavir (100 mg) should be administered simultaneously with, or at least 10 hours after, the H₂-receptor antagonist.
  

For treatment-experienced patients who are receiving atazanavir and require PPIs or H₂-receptor antagonists:

• PPIs should not be used in treatment-experienced patients receiving atazanavir.
  
• The H₂-receptor–antagonist dose should not exceed the dose-equivalent of twice-daily 20-mg famotidine. Atazanavir and ritonavir should be administered simultaneously with, or at least 10 hours after, the H₂-receptor antagonist. The recommended dose of atazanavir with ritonavir depends on whether the patient is also taking tenofovir. If a patient’s regimen does not include tenofovir, 300 mg of atazanavir (one 300-mg capsule or two 150-mg capsules) should be given with 100 mg of ritonavir, both once daily (all as a single dose with food). If a patient’s regimen does include tenofovir, 400 mg of atazanavir (two 200-mg capsules) should be given with 100 mg of ritonavir, both once daily (all as a single dose with food).
  

Renal Failure

• The dosing of atazanavir does not need to be adjusted for patients with renal impairment, including those with severe renal impairment who are not managed with hemodialysis.
  
• Treatment-naive patients with end-stage renal disease managed with hemodialysis should receive 300 mg of atazanavir with 100 mg of ritonavir.
  
• Atazanavir should not be administered to treatment-experienced patients with end-stage renal disease managed with hemodialysis.
  

Comment: Atazanavir has become the most widely used PI for initial therapy because of its once-daily dosing, low pill burden, and favorable metabolic profile. However, this latest revision to the package insert (the eighth since the drug’s release) highlights two nettlesome drug–drug interactions that increase the complexity of its use: the reduction in atazanavir levels with tenofovir and the decreased absorption of atazanavir when it is given with acid-reducing therapies. The distinction in atazanavir dosing between treatment-naive and treatment-experienced patients is related to the higher target concentrations required for successful treatment of the latter, especially those with prior PI experience. Patients with end-stage renal disease on hemodialysis seem to attain lower levels of atazanavir; hence, in this population, this drug should be used only with ritonavir boosting and in treatment-naive patients.

— Paul E. Sax, MD

Published in AIDS Clinical Care January 28, 2008

Citation(s):

Reyataz (atazanavir sulfate) capsules [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; Dec 2007. (http://www.fda.gov/cder/foi/label/2007/021567s014lbl.pdf)