Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir + Omeprazole = Precautionary

Effect on Concentration

Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
No change
Applies within class?
No
Omeprazole
Decrease
Applies within class?
No

Pharmacologic Effects

Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Effect
N/A
Applies within class?
No
Omeprazole
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 13-Jul-2018

Summary

Sources

Drug–Drug Interaction of Omeprazole With the HCV Direct‐Acting Antiviral Agents Paritaprevir/Ritonavir and Ombitasvir With and Without Dasabuvir. ^

Study Design

This was a 2-period, crossover study in 12 healthy subjects to evaluate drug-drug interactions between Paritaprevir/Ritonavir/Ombitasvir + Dasabuvir (ABT-450/r/ABT-267 + ABT-333, also known as 3D regimen) and omeprazole. The 3D drugs were dosed as paritaprevir/ritonavir 150/100mg QD, ombitasvir 25mg QD, and dasabuvir 400mg BID or 250mg BID (the two strengths were from two different formulations which provided similar exposures). The omeprazole dose administered was 40mg. In period 1, omeprazole was given as a single dose followed by a washout period. During period 2, the 3D regimen was given alone on days 6-19, followed by the 3D regimen + omeprazole on days 20-24. Blood samples for pharmacokinetic (PK) analyses were collected following dosing of omeprazole, 3D regimen, and omeprazole + 3D regimen.

Study Results

Using Least Squares Mean (LSM) ratios and corresponding 90% confidence intervals, the Cmax and AUC for ombitasvir were 1.02 (0.95-1.09) and 1.05 (0.98-1.12) respectively. Those for dasabuvir were 1.13 (1.03-1.25) and 1.08 (0.98-1.20). Those for paritaprevir were 1.19 (1.04-1.36) and 1.18 (1.03-1.37). And those for ritonavir were 1.04 (0.96-1.12) and 1.02 (0.97-1.08) respectively, when these were co-administered with omeprazole. The LSM ratios and 90% CI for omeprazole Cmax and AUC when coadministered with the 3D regimen were 0.62 (0.48-0.80) and 0.62 (0.51-0.75) respectively. A higher dose of omeprazole could be considered if clinically indicated. Monitor patients for decreased efficacy of omeprazole. Consider increasing the omeprazole dose in patients whose symptoms are not well controlled; avoid use of more than 40 mg per day of omeprazole.

Study Conclusions

**The authors used data from phase 2 studies to determine that an increase in exposure by 100% or a decrease by 50% did not have a clinically meaningful effect on the safety or efficacy profile of the 3D regimen.

References

Polepally AR, Dutta S, Hu B, Podsadecki TJ, Awni WM, Menon RM. Drug–drug interaction of omeprazole with the hcv direct‐acting antiviral agents paritaprevir/ritonavir and ombitasvir with and without dasabuvir. Clinical Pharmacology In Drug Development. 2016; 4: 269-277.