Ombitasvir/Paritaprevir/Ritonavir + Ketoconazole = Precautionary

Effect on Concentration

Ombitasvir/Paritaprevir/Ritonavir
Increase
Applies within class?
No
Ketoconazole
No change
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Per the author's recommendations, limit Ketoconazole and Itraconazole levels to = 200mg per day in order to offset the increases in exposure observed. Lower doses are recommended for posaconazole. This interaction is thought to occur via the CYP3A Pathway.

Sources

Ombitasvir/Paritaprevir/Ritonavir vs Ketoconazole ^

Study Design

Eight one sequence crossover, drug-drug interaction studies were conducted to assess the impact on PK values for the 2D regimen, Ombitasvir (25mg daily) + Paritaprevir/Ritonavir (150/100mg).These studies were conducted in healthy volunteers aged 18 to 55 years of age. A total of 12 participants were included in the evaluation of Ketoconazole vs. 2D Regimen.The 2D regimen was administered alone on Day 1. This was followed by a washout period on Days 2 through 7. On Days 8 and 9, Ketoconazole (400mg QD) was administed alone. On Day 10, the 2D regimen was administered with Ketoconazole. On Days 11 through 13, Ketoconazole was administered alone.

Study Results

DrugCmax GMR (90% CI)AUC GMR (90% CI)Ombitasvir0.98 (0.92-1.04)1.26 (1.20-1.32)Paritaprevir1.72 (1.32-2.26)2.16 (1.76-2.66)Ritonavir1.27 (1.11-1.46)1.51 (1.36-1.68)Ketoconazole1.10 (1.05-1.15)2.05 (1.93-2.18)Co-administration of Ketoconazole and the 2D regimen can potentially cause a clinically significant increase in Cmax and AUC for Ketoconazole as well as the 2D regimen.

Study Conclusions

References

P Badri, S Dutta, H Wang, et al. Drug interactions with direct acting antiviral combination of paritaprevir/ritonavir ombitasvir. 16th International Workshop On Clinical Pharmacology Of Hiv ; Hepatitis Therapy. Washington, DC. ; 2015.