Alisporivir + Azithromycin = Precautionary

Effect on Concentration

Alisporivir
No change
Applies within class?
No
Azithromycin
Increase
Applies within class?
No

Pharmacologic Effects

Alisporivir
Effect
N/A
Applies within class?
No
Azithromycin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-May-2020

Summary

The coadministration of alisporovir and azithromycin resulted in no change on the pharmacokinetics of alisporovir while increase in exposure was observed for azithromycin.

Sources

The Effects of CYP3A4 Induction and Inhibition on the Pharmacokinetics of Alisporivir in Humans ^

Study Design

In vitro data suggest that alisporivir is a substrate and inhibitor of CYP3A4 and P-gp. Hence, the potential for drug-drug interactions when alisporivir is co-administered with CYP3A4 and/or P-gp inhibitors such as ketoconazole, azithromycin and CYP3A4 inducers such as rifampin were evaluated in three separate clinical studies.

Study Results

Co-administration with ketoconazole (a strong CYP3A4 inhibitor) increased the Cmax , AUC and terminal elimination half-life of alisporivir by approximately two-, eight- ,and threefold, respectively. Co-administration with azithromycin (a putative weak CYP3A4 inhibitor and substrate) had no impact on the Cmax and AUC of alisporivir. Rifampin (a CYP3A4 inducer) caused an approximate 90 reduction in alisporivir Cmax and AUC and a fourfold reduction in alisporivir terminal elimination half-life. Alisporivir as an inhibitor of CYP3A4 caused a 39 increase in azithromycin exposure.

Study Conclusions

The results from these studies establish alisporivir as a sensitive CYP3A4 substrate in vivo. Consequently, co-administered potent CYP3A4 inhibitors and inducers are likely to cause clinically significant changes in the exposure to alisporivir.

References

Barve A. The effects of cyp3a4 induction and inhibition on the pharmacokinetics of alisporivir in humans. Clin Pharmacol Drug Dev. 2015; 1: 25-32.