Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir + Valsartan = Precautionary

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

Caution should be used when paritaprevir/ritonavir/ombitasvir + dasabuvir (ABT-450/r/ABT-267 + ABT-333, also known as 3D regimen) is coadministered with valsartan or other substrates of OATP1B or BCRP. The 3D regimen inhibits these transporters and can increase plamsa concentrations of valsartan, and increase the risk for adverse events.The authors recommend dose adjustment (reduction) of valsartan during coadministration with the 3D regimen. Close monitoring is warranted.*This interaction has not been formerly studied.

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.