Atazanavir versus Raniditine
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Study Design
Cimetidine has not been directly studied with ritonavir boosted atazanavir, but data can be extrapolated from interaction studies between ritonavir boosted atazanavir and the histamine-2 receptor antagonist famotidine. In healthy subjects, famotidine, an H2-receptor antagonist, reduces exposures of atazanavir by 4–28% at doses of 20–40 mg twice daily. This study evaluated the effect of famotidine 20–40 mg twice daily on the pharmacokinetics of atazanavir/ritonavir 300/100 mg once daily with and without tenofovir disoproxil fumarate (TDF) 300 mg in HIV-infected patients (n=40; 87.5% male; mean age 42, range 26–63 years; 55% white).
Study Results
Coadministration of famotidine 40 mg and atazanavir/ritonavir to HIV-infected patients reduced exposures of atazanavir by approximately 20%. This is comparable to reductions seen in HIV-uninfected subjects. Coadministration of famotidine 20 mg had less impact on atazanavir exposures, with no reduction of atazanavir geometric mean plasma concentration at 24 h postdose (Cmin). In the presence of TDF, administration of famotidine 20–40 mg twice daily 2 h after and 10 h before atazanavir/ritonavir reduced exposures of atazanavir by 19–25%. However, all individual atazanavir Cmin values remained at least five-fold above the population mean protein-binding adjusted 90% maximum effect (EC90) against wild-type HIV (14 ng/mL). No viral load rebound was observed at end of study.
Study Conclusions
The US Prescribing Information states that in TREATMENT NAIVE patients, famotidine should not exceed 40 mg twice daily and atazanavir/ritonavir should be dosed at 300/100 mg once daily either with or at least 10 h after famotidine. For patients unable to tolerate ritonavir (who are not pregnant), atazanavir 400 mg once daily with food should be administered at least 2 hours before and at least 10 hours after a dose of famotidine. In TREATMENT EXPERIENCED patients, famotidine should not exceed 20 mg twice daily and atazanavir/ritonavir should be dosed at 300/100 mg once daily either with or at least 10 h after famotidine. In TREATMENT EXPERIENCED patients WITH TENOFOVIR atazanavir/ritonavir should be increased to 400/100 mg once daily either with or at least 10 h after famotidine. In TREATMENT EXPERIENCED pregnant patients atazanavir/ritonavir should be increased to 400/100 mg once daily either with or at least 10 h after famotidine during the second and third trimester. Atazanavir is not recommended for pregnant women during the second and third trimester taking both tenofovir and an H2RA.
References
Wang X, Boffito M, Zhang J, Chung E, Zhu L, Wu Y, Mahnke L. Effects of the h2-receptor antagonist famotidine on the pharmacokinetics of atazanavir-ritonavir with or without tenofovir in hiv-infected patients. Aids Patient Care & Stds. 2011; 9: 509-515.
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