Telaprevir + Tacrolimus = Precautionary

Effect on Concentration

Telaprevir
No change
Applies within class?
No
Tacrolimus
Increase
Applies within class?
No

Pharmacologic Effects

Telaprevir
Effect
N/A
Applies within class?
No
Tacrolimus
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 10-Jul-2018

Summary

Sources

Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus ^

Study Design

This was a phase 1, open-label, non-randomized, single-sequence study in healthy volunteers. 10 subjects were enrolled into the portion of the study examining the effect of co-administration of telaprevir on cyclosporine. In period 1, subjects received a 100mg oral dose of cyclosporine, followed by an 8 day washout. In period 2, subjects received telaprevir 750mg every 8 hours on days 1-11, and a single 10mg oral dose of cyclosporine on days 1 and 8 (separated by 2 hours from telaprevir administration).

Study Results

Nine volunteers received at least one dose of cyclosporine co-administered with telaprevir, of which the majority were female. When cyclosporine was co-administered with telaprevir during period 2, a 4.11-fold and 4.64-fold increase in the AUC0-8 (dose normalized to 1mg) of cyclosporine occurred on day 1 and day 8, respectively. The dose normalized Cmax of cyclosporine increased by approximately 1.35-fold in period 2, on days 1 and 8. As well, during co-administration an approximately 4-fold increase in cyclosporine t1/2 was seen on day 1 and on day 8 in period 2. Telaprevir kinetics were similar to historical data, suggesting no major effect of cyclosporine on telaprevir.

Study Conclusions

The manufacturer states that significant dose reduction and prolongation of the dosing interval of the immunosuppressant to achieve desired blood levels should be anticipated. Close monitoring of immunosuppressant blood levels, renal function, and side-effects are recommended. The use of telaprevir in organ transplant (pre, post, or peri) patients has not been studied. The authors advise that telaprevir should not be administered to these patients since studies have not been performed to understand how to dose adjust for safe administration and regulatory approval has not been obtained. Also, careful blood monitoring is recommended after telaprevir is discontinued until it's inhibitory effect on immunosuppressant blood levels has worn off.

References

Garg V, van Heeswijk R, Lee EJ, Alves K, Nadkarni P, Luo X. Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus. Hepatology. 2011; 1: 20-27.