Bristol Myers Squibb has warned doctors that combining the company's new protease inhibitor atazanavir (Reyataz) with tenofovir may risk treatment failure, due to an interaction that reduces atazanavir levels by up to 40%. Doctors should consider boosting atazanavir levels with ritonavir, using the 300/100mg dose, if atazanavir and tenofovir must be used together, a letter to health care providers states.
The company has released details of a study in healthy volunteers (study AI454-181), which showed that when dosed alone with tenofovir, atazanavir trough (Cmin) levels were reduced by 40% (range 32-48%) and total exposure (AUC) was reduced by 25% (range 19-30%). This study assigned 34 individuals to receive either atazanavir 400mg qd with a light meal, or atazanavir 400mg qd plus tenofovir 300mg with a light meal.
In this study, total tenofovir exposure (AUC) was increased by 25%.
A study in ten treatment experienced individuals (ANRS 107, or Puzzle 2) showed that when boosted with 100mg of ritonavir and dosed with tenofovir, atazanavir trough levels were reduced by 23% and total exposure (AUC) by 25%. However, the AUC and Cmin still remained above the levels observed for atazanavir 400mg qd dosed without tenofovir (513ng/ml vs 118ng/ml).
Based on these results, Bristol Myers Squibb has warned that:
- Clinicians should use caution when administering atazanavir unboosted with tenofovir – atazanavir may be less effective.
- Ritonavir boosting of atazanavir should be considered if atazanavir and tenofovir are to be used together.