Liverpool HIV Interactions

Do Not Coadminister

_ZZAtazanavir

Lansoprazole

Quality of Evidence: Low

Summary:

Coadministration of atazanavir with proton pump inhibitors is not recommended. Lansoprazole decreased atazanavir (alone) AUC by 94%; omeprazole decreased atazanavir (+ ritonavir) AUC by 75%. If coadministration is judged unavoidable, close clinical monitoring is recommended and doses of proton pump inhibitors comparable to omeprazole 20 mg should not be exceeded and must be taken approximately 12 hours prior to the atazanavir/ritonavir. The European SPC recommends increasing the dose of atazanavir to 400 mg with 100 mg of ritonavir.

Description:

Co-administration of atazanavir with proton pump inhibitors is not recommended. If the combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir; doses of proton pump inhibitors comparable to omeprazole 20 mg should not be exceeded. Coadministration of omeprazole (40 mg once daily) 2 hours before atazanavir/ritonavir (300/100 mg once daily) decreased atazanavir AUC, Cmax, and Cmin by 61%, 66% and 65%, respectively. Coadministration of omeprazole (20 mg once daily) 1 hour before an increased dose of atazanavir and ritonavir (400/100 mg once daily) decreased atazanavir AUC, Cmax and Cmin by 30%, 31% and 31%, relative to atazanavir and ritonavir (300/100 mg once daily) without omeprazole. The decrease in AUC, Cmax and Cmin was not mitigated when an increased dose of atazanavir and ritonavir (400/100 mg once daily) was temporally separated from omeprazole by 12 hours. Although not studied, similar results are expected with other proton pump inhibitors. This decrease in atazanavir exposure might negatively impact the efficacy of atazanavir. The mechanism of interaction is decreased solubility of atazanavir as intra-gastric pH increases with proton pump inhibitors.
Reyataz Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, April 2014.

Plasma concentrations of atazanavir were substantially decreased when atazanavir 400 mg or atazanavir 300 mg/ritonavir 100 mg once daily was administered with omeprazole 40 mg once daily in adults, which may result in loss of therapeutic effect and development of resistance. In treatment-naive adult patients, the proton-pump inhibitor (PPI) dose should not exceed a dose comparable to omeprazole 20 mg and must be taken approximately 12 hours prior to the atazanavir 300 mg with ritonavir 100 mg dose. In treatment-experienced adult patients, the use of PPIs in treatment-experienced patients receiving atazanavir is not recommended.
Reyataz Prescribing Information, Bristol-Myers Squibb Co, September 2015.

The pharmacokinetics of atazanavir (400 mg single doses) were determined alone and in the presence of lansoprazole (60 mg, 1 dose 24 h prior to and 1 dose with atazanavir) in 9 healthy subjects. Absorption of atazanavir was significantly reduced when coadministered with lansoprazole; AUC decreased by 94% from 16.3±9.0 to 0.95±1.8 µM.h. Cmax decreased from 3.2±1.7 to 0.13±0.19 µM. Based on these results atazanavir should not be coadministered with lansoprazole or other proton pump inhibitors

Inhibition of atazanavir oral absorption by lansoprazole gastric acid suppression in healthy volunteers. Tomilo DL, Smith PF, Ogundele AB, et al. Pharmacotherapy, 2006, 26: 341-346.

A case report described the absence of an interaction with atazanavir/ritonavir and lansoprazole. A 40-year old HIV+ man received atazanavir/ritonavir (300/100 mg once daily), tenofovir and lamivudine with lansoprazole (30 mg twice daily). Atazanavir concentrations determined pre- and 2 h post dose were 400 ng/ml and 720 ng/ml, respectively. Further samples were collected at 1, 3, 5 and 7 h post dose; using these concentrations, a 24h AUC was calculated as 46910 ng.h/ml. Despite coadministration of both lansoprazole and tenofovir, the patient’s plasma concentrations remained consistent with historical values, with a trough concentration well above the established values for atazanavir/ritonavir/tenofovir. His viral load remained undetectable and he continued immunological stability.
Lack of interaction between atazanavir and lansoprazole. Kosel BW, Storey SS, Collier AC. AIDS, 2005, 19(6): 637-638.

Trough atazanavir concentrations were available in 15 patients receiving a proton pump inhibitor (PPI) and 19 patients receiving an H2 receptor antagonist (H2). The mean atazanavir trough concentration in the PPI group was 0.65 µg/ml (range <0.05 to 1.85 µg/ml) compared to 1.12 µg/ml (range <0.05 to 3.17 µg/ml) in the H2 group. Concentrations were below target (0.27 µg/ml) in 6/15 in the PPI group, even though 5 of these were receiving boosted atazanavir. Inadequate levels were observed in 4/20 in the H2 group, 2 of whom were receiving boosted atazanavir. These results suggest a negative effect of proton pump inhibitors and H2 receptor antagonists on atazanavir concentrations and that boosting with ritonavir does not ensure adequate concentrations. Further study of this important issue is warranted.
Coadministration of atazanavir with proton-pump inhibitors and H2-blockers. Farthing C, Khanlou H. 7th International Congress on Drug Therapy in HIV Infection, Glasgow, November 2004, abstract P289.

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