December 2004
Dear Health Care Provider,
Bristol-Myers Squibb Company would like to make clinicians caring for HIV-infected patients aware of important new pharmacokinetic data concerning the coadministration of REYATAZ and Norvir (ritonavir, Abbott Laboratories, Inc.) with Prilosec® (omeprazole, AstraZeneca), a proton-pump inhibitor (PPI).
The following observations were made from a randomized, open-label, multiple-dose drug interaction study:
A 76% reduction in atazanavir area under the concentration-time curve (AUC) and a 78% reduction in atazanavir trough plasma concentration (Cmin) was observed when REYATAZ/ritonavir (RTV) 300/100 mg was coadministered with omeprazole 40 mg.
STUDY INFORMATION:
The table below shows data from a randomized, open-label, multiple-dose drug interaction study in healthy, HIV-uninfected subjects assessing comparability of the steady-state pharmacokinetics of REYATAZ/RTV 300/100 mg once daily (n=15), REYATAZ/RTV 300/100 mg with 8 ounces of cola once daily (n=15), and REYATAZ/RTV 400/100 mg once daily (n=14), each administered with omeprazole 40 mg once daily for 10 days. Subjects in each treatment arm received REYATAZ/RTV 300/100 mg for 10 days prior to randomization to one of the three treatment sequences and the addition of omeprazole on Day 10. In all cases, REYATAZ/RTV was administered with a light meal, and omeprazole was administered on an empty stomach 2 hours prior to REYATAZ/RTV.
Pharmacokinetic Parameters for REYATAZ (Geometric Mean Ratios [90% confidence interval] and % Reduction as compared to REYATAZ/RTV 300/100 mg not coadministered with omeprazole)1
| Pharmacokinetic Parameter |
ATV/RTV 300/100 mg + omeprazole 40 mg once daily |
ATV/RTV 300/100 mg + omeprazole 40 mg + 8 oz of cola once daily |
ATV/RTV 400/100 mg + omeprazole 40 mg once daily |
|---|---|---|---|
| Cmax (ng/mL) % Reduction in Cmax |
0.279 (0.242, 0.321) 72 |
0.337 (0.293, 0.388) 66 |
0.437 (0.378, 0.506) 56 |
| AUC(TAU) (ngïhr/mL) % Reduction in AUC |
0.240 (0.211, 0.274) 76 |
0.301 (0.265, 0.343) 70 |
0.394 (0.345, 0.451) 61 |
| Cmin (ng/mL) % Reduction in Cmin |
0.223 (0.188, 0.264) 78 |
0.271 (0.228, 0.321) 73 |
0.345 (0.289, 0.411) 66 |
ATV = atazanavir, RTV = ritonavir , Cmax = peak plasma concentration, AUC(TAU) = area under the plasma concentration-time curve in one dosing interval, Cmin = trough plasma concentration
Investigations regarding the potential drug interaction between REYATAZ (atazanavir sulfate) and H2-Receptor antagonists when coadministered are ongoing. Until data are available, clinicians should note the following statements from the REYATAZ Package Insert: ìReduced plasma concentrations of atazanavir are expected if 2-receptor antagonists are administered with REYATAZ (atazanavir sulfate). This may result in loss of therapeutic effect and development of resistance. To lessen the effect of H2-receptor antagonists on atazanavir exposure, it is recommended that an H2-receptor antagonist and REYATAZ be administered as far apart as possible, preferably 12 hours apart.î
Please refer to the accompanying REYATAZ Indication and Important Safety Information, and the enclosed Full Prescribing Information.
BMS is committed to providing you with current product information for the management of your patients with HIV infection. If you have any questions about this new information or require additional medical information, please contact the Virology Medical Services Department at Bristol-Myers Squibb Company at 1-800-426-7644 (select Option 3).
Sincerely,
Sally L. Hodder, MD
Vice President, Virology Medical Affairs
Bristol-Myers Squibb Company
REYATAZ is a registered trademark of Bristol-Myers Squibb Company. All other trademarks are the property of their respective owners and are not trademarks of Bristol-Myers Squibb Company.
Enclosures:
REYATAZ® (atazanavir sulfate) Package Insert
Important Information about REYATAZ
1. Data on file, Bristol-Myers Squibb Company, Princeton, New Jersey.
INDICATION: Reyataz (atazanavir sulfate) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection This indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts from controlled studies of 48 weeks duration in antiretroviral-naive patients and antiretroviral-treatment-experienced patients. The following points should be considered when initiating therapy with Reyataz :
In therapy-naÔve patients, REYATAZ 400 mg should be taken once daily with food. In therapy-experienced patients, REYATAZ 300 mg plus ritonavir 100 mg should be taken once daily with food. Efficacy and safety of REYATAZ with ritonavir in doses greater than 100 mg once daily have not been established. Prescribers should consult the complete prescribing information for Norvir® (ritonavir) when using this agent.
Please refer to the enclosed REYATAZ Full Prescribing Information.
F1-W0004 12-04