Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir + Midazolam = Prohibited

Effect on Concentration

Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
Unknown
Applies within class?
No
Midazolam
Unknown
Applies within class?
No

Pharmacologic Effects

Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir
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

Midazolam is a major CYP3A substrate and its exposure may be significantly increased when co-administered with the 3D regimen. The manufacturer states that this combination is contraindicated.

Sources

Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir vs Midazolam ^

Study Design

This was a 2-period, crossover study in 12 healthy subjects to evaluate drug-drug interactions between Paritaprevir/Ritonavir/Ombitasvir + Dasabuvir (ABT-450/r/ABT-267 + ABT-333, also known as 3D regimen) and escitalopram. The 3D drugs were dosed as paritaprevir/ritonavir 150/100mg QD, ombitasvir 25mg QD, and dasabuvir 400mg BID or 250mg BID (the two strengths were from two different formulations which provided similar exposures). The escitalopram dose administered was 10mg.In period 1 escitalopram was given as a single dose, followed by a washout period. During period 2, the 3D regimen was given alone on days 7-20, followed by the 3D regimen + escitalopram on day 21, then the 3D regimen alone on days 22-26. Blood samples for pharmacokinetic (PK) analyses were collected following dosing of escitalopram, 3D regimen, and escitalopram + 3D regimen.

Study Results

Study Conclusions

References

R Menon, P Badri, U Das, et al. Drug-drug interactions with direct-acting antiviral combination therapy of abt-450/r, ombitasvir, and dasabuvir. 54th Interscience Conference On Antimicrobial Agents And Chemotherapy. Washington, DC. ; 2014.