Ledipasvir (Single Agent) + Midazolam = Unknown or no reaction

Effect on Concentration

Ledipasvir (Single Agent)
Unknown
Applies within class?
No
Midazolam
No change
Applies within class?
No

Pharmacologic Effects

Ledipasvir (Single Agent)
Effect
N/A
Applies within class?
No
Midazolam
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

According to the study authors, LDV did not alter midazolam pharmacokinetics, and drugs can be administered concomittantly without dose adjustment.

Sources

Ledipasvir vs midazolam ^

Study Design

Thirty healthy subjects were enrolled in this fixed sequence, open label study. A single dose of midazolam 2.5 mg was administered alone on Day 1, was coadministered with a single dose of ledipasvir (LDV) 90 mg on day three, and on day 13 coadminstered with 90 mg of LDV following daily dosing of LDV 90 mg on days 4-12. The pharmacokinetics of midazolam were assessed on days 1, 3, and 13, while the PK of LDV was assessed on days 3 and 13. Statistical analysis using GMR of AUC and Cmax of midazolam using MDZ pharmacokinetics on days 3 and 13 compared with when it was dosed alone on day 1 were done using a no-interaction boundary of 70-143%. Safety was assessed using laboratory and clinical markers.

Study Results

Relative to when midazolam was administered alone on day 1, the GMR% of midazolam AUC was 99.3 (95.3, 103) and Cmax was 107 (100, 114) on day 3. The GMR% of midazolam AUC was 89.5 (84, 95.4) and Cmax was 95 (86.7, 104) on day thirteen. The single and multiple dose exposures of LDV were similar to historical data. All treatments were safe and well tolerated.

Study Conclusions

References

N Au, P German, Y Li, G Shen, C Yun, Ling KH. Lack of an effect of ledipasvir on cyp3a activity in healthy volunteers.in. 17th International Workshop On Clinical Pharmacology Of Hiv And Hepatitis Therapy. Washington, DC. ; 2016.