Atazanavir/Ritonavir + Ledipasvir/Sofosbuvir = Unknown or no reaction

Effect on Concentration

Atazanavir/Ritonavir
No change
Applies within class?
No
Ledipasvir/Sofosbuvir
No change
Applies within class?
No

Pharmacologic Effects

Atazanavir/Ritonavir
Effect
N/A
Applies within class?
No
Ledipasvir/Sofosbuvir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

If tenofovir DF is used as part of the NRTI combination, monitoring for TFV associated adverse events should be warranted.

Sources

Drug–Drug Interaction Profile of the Fixed-Dose Combination Tablet Regimen Ledipasvir/Sofosbuvir. ^

Study Design

In a Phase 1, multiple-dose, randomized, cross-over study in healthy subjects, the drug-drug interaction potential between ledipasvir/sofosbuvir (LDV/SOF) (90/400mg) and atazanavir/ritonavir (ATV/r) 300/100mg plus emtricitabine and tenofovir DF (FTC/TDF = TVD) 200mg/300mg was evaluated. Agents were administered once daily and both simultaneous dosing and 12-hr staggered dosing schedules were analyzed. Treatments were administered for 10 days in each group. Geometric least-squares means ratios % and 90% confidence intervals (combination vs. alone) for LDV, SOF, GS-331007, and ATV/r, FTC and tenofovir (TFV) PK parameters were estimated and compared against pre-specified lack of PK alteration boundaries of 70-143%.

Study Results

Change in PK parameter Simultaneous 12-hour Stagger ATV/RTV + TVD with LDV/SOF vs. ATV/RTV + TVD ATV RTV FTC TFV ATV RTV FTC TFV AUCtau ? ? ? ? ?43% ? ? ? Cmax ? ? ? ?47% ? ? ? ?46% Ctau ?63% ?45% ? ?47% ?108% ?70% ? ?38% ATV/RTV + TVD with LDV/SOF vs. LDV/SOF LDV SOF GS-331007 LDV SOF GS-331007 AUCtau ?96% ? ? ?134% ? ?50% Cmax ?68% ? ? ?75% ? ? Ctau ?118% N/A ?42% ?164% N/A ? Note: 90% CI of the geometric least square mean ratios were within (?), extended above (?), or extended below (?) the predetermined lack of PK alteration boundaries of 70% - 143%; N/A: not estimated.

Study Conclusions

The authors state that alternative HCV or antiretroviral therapy should be considered. Close monitoring for TFV-associated adverse events is advised if this combination is utilized.

References

German P, Mathias A, Brainard DM, Kearney BP. Drug–drug interaction profile of the fixed-dose combination tablet regimen ledipasvir/sofosbuvir. Clinical Pharmacokinetics. 2018; : 1-15.