Atazanavir + Famotidine = Precautionary

Effect on Concentration

Atazanavir
Decrease
Applies within class?
No
Famotidine
No change
Applies within class?
No

Pharmacologic Effects

Atazanavir
Effect
N/A
Applies within class?
No
Famotidine
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 17-Jul-2018

Summary

Sources

Atazanavir versus Famotidine ^

Study Design

Pharmacokinetics of atazanavir and famotidine were studied when these drugs were used concomitantly.

Study Results

When famotidine (FAM) was simultaneously coadministered with unbooosted ATV, ATV PK parameters were significantly decreased (approximately 40-50%) compared to ATV 400 mg administered alone; however, the ATV PK parameters were not altered when ATV was administered 10 hours after or 2 hours before FAM. When FAM was simultaneously coadministered with ritonavir-boosted ATV (ATV/r), ATV PK parameters were modestly decreased compared to ATV/r administered alone. When ATV/r 300/100 mg once daily administered simultaneously with FAM 20 or 40 mg BID, there was approximately 20-30% decrease in ATV PK parameters compared to ATV/r 300/100 mg administered alone. It was noted that these PK values were significantly higher than PK values of ATV 400 mg administered alone; no change in ATV Cmax, a 1.79-fold higher in AUC, and 4.46-fold higher in Cmin. When FAM 20 mg BID was simultaneously coadministered with ATV/r 300/100 mg QD plus TFV 300 mg QD, there was modest decrease in ATV PK parameters by approximately 10-20 %. Similar decrease was shown when ATV/r 300/100 mg plus TFV 300 mg once daily were administered 12 hours after the evening FAM 40 mg QD. When FAM 40 mg BID was coadministered with ATV/r 400/100 mg QD plus TFV 300 mg QD simultaneously, ATV exposures was similar with when ATV/r 300/100 mg was administered without FAM. When FAM dose was decreased to 20 mg BID, ATV PK parameters were modestly increased (approximately 20%) compared to ATV 300/100 mg QD without FAM. reference population FAM (dose/freq) ATV or ATV/r (dose/ freq) TFV (dose/freq) administration PK parameters (90% CI) of ATV Cmax AUC Cmin Agarwala S.et al. healthy (n=16) 40 mg BID 400 mg QD simultaneous 0.58 0.62 0.6 REYATAZ® healthy (n=15) 0.53 (0.34, 0.82) 0.59 (0.40, 0.87) 0.58 (0.37, 0.89) REYATAZ® healthy (n=14) 10 hr after, 2 hr before FAM 1.08 (0.82, 1.41) 0.95 (0.74, 1.21) 0.79 (0.60, 1.04) Wang X. et al HIV-infected (n=18) 20 mg BID 300/100 mg QD simultaneous 0.80 (0.68, 0.93) 0.87 (0.75, 1.01) 0.99 (0.84, 1.18) HIV-infected (n=18) 40 mg BID 0.77 (0.67, 0.88) 0.77 (0.68, 0.86) 0.80 (0.69, 0.92) REYATAZ® ? (n=14) 0.86 (0.79, 0.94) 0.82 (0.75, 0.89) 0.72 (0.64, 0.81) Wang X. et al HIV-infected (n=18) 20 mg BID 300/100 mg QD 300 mg QD 10 hr after, 2 hr before FAM 0.79 (0.64, 0.96) 0.79 (0.66, 0.96) 0.81 (0.63, 1.05) REYATAZ® ? (n=18) simultaneous 0.91 (0.84, 0.99) 0.90 (0.82, 0.98) 0.81 (0.69, 0.94) Wang X. et al HIV-infected (n=18) 40 mg BID 300/100 mg QD 300 mg QD 10 hr after, 2 hr before FAM 0.77 (0.64, 0.92) 0.76 (0.64, 0.89) 0.75 (0.53, 1.07) REYATAZ® ? (n=18) 0.74 (0.66, 0.84) 0.79 (0.70, 0.88) 0.72 (0.63, 0.83) REYATAZ® ? (n=20) 12 hr after FAM 0.89 (0.81, 0.97) 0.88 (0.80, 0.96) 0.77 (0.63, 0.93) Chung et al. HIV-infected (n=24) 20 mg BID 400/100 mg QD 300 mg QD simultaneous 1.18 (1.07, 1.31) 1.18 (1.07, 1.30) 1.24 (1.10, 1.39) HIV-infected (n=24) 40 mg BID 400/100 mg QD 300 mg QD simultaneous 0.95 (0.83, 1.08) 0.98

Study Conclusions

In clinical trials, concomitant use of unboosted ATV and FAM has resulted in reduced ATV plasma concentrations and exposure, which may result in loss of ATV efficacy and development of resistance.For a patient receiving a FAM, ATV/r 300/100 mg QD simultaneously with and/or at least 10 hours after the FAM is recommended.

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.