Dasabuvir/Ombitasvir/Paritaprevir/Ritonavir + Carbamazepine = Prohibited

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

Using Least Squares Mean (LSM) ratios and corresponding 90% confidence intervals, the Cmax and AUC for ombitasvir were 0.69 (0.61-0.78) and 0.70 (0.64-0.75) respectively. Those for dasabuvir were 0.45 (0.41-0.50) and 0.30 (0.27-0.33). Those for paritaprevir were 0.34 (0.25-0.48) and 0.30 (0.23-0.37). And those for ritonavir were 0.17 (0.12-0.24) and 0.13 (0.09-0.17) respectively, when these were co-administered with carbamazepine.The LSM ratios and 90% CI for carbamazepine Cmax and AUC when coadministered with the 3D regimen were 1.10 (1.07-1.14) and 1.17 (1.13-1.22) respectively.Co-administration of carbamazepine with the 3D regimen is contraindicated due to the decrease in PK parameters of the direct-acting antiviral drugs beyond the no-effect boundary as observed in phase 2 studies.

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.