Sofosbuvir with Daclatasvir and Ribavirin (Complete Regimen) + Tacrolimus = Precautionary

Effect on Concentration

Sofosbuvir with Daclatasvir and Ribavirin (Complete Regimen)
No change
Applies within class?
No
Tacrolimus
Decrease
Applies within class?
No

Pharmacologic Effects

Sofosbuvir with Daclatasvir and Ribavirin (Complete Regimen)
Effect
N/A
Applies within class?
No
Tacrolimus
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 20-Jul-2018

Summary

Sources

Sofosbuvir/Daclatasvir/Ribavirin versus Tacrolimus ^

Study Design

This was a cohort study in liver transplant patients aged >18 years-old whom had hepatitis C infection before transplantation and whom had HCV recurrence with a detectable HCV RNA before enrollment in the cohort. There were (n=12) subjects in the Sofosbuvir/Daclatasvir/Ribavirin treatment group who received Sofosbuvir (SOF) 400mg daily with Daclatasvir (DCV) 60mg daily or (90mg daily if on Efavirenz) and Ribavirin (dose not reported).. Subjects were administered Tacrolimus (TAC) BID or daily and dosed appropriately to achieve optimal blood concentrations at that time post transplantation. Blood samples were drawn for TAC before DAA initiation (D0) and at week 4 (W4). Trough concentrations (C0) of TAC at steady state were measured. W4/D0 geometric mean ratio (GMR) and 2 sided 90% confidence interval (CI90) were calculated for Cl/F, this was then compared to the 0.80-1.25 bioequivalence range.

Study Results

For SOF/DCV/RBV patients on TAC results showed a GMR of 1.69 with CI90 of (1.20, 2.38)

Study Conclusions

The authors concluded that there was an increased TAC clearance when given together with Sofosbuvir/Daclatasvir/Ribavirin. This increase indicates that liver transplant patients should be given close monitoring during DAA therapy though specifics for dose monitoring or adjustment were not provided. Given the narrow therapeutic window of tacrolimus, use extra precaution when using these drugs concomitantly

References

Taburet M, Barrail-Tran G, LaForest C, Pageux AP. Effect of direct acting antivirals on the pharmacokinetics of calcineurin inhibitors [abstract 455]. Conference On Retroviruses And Opportunistic Infections. Boston, MA, USA. 2016; February 2016.