erefore, dasabuvir is not expected to affect medicinal products which are primarily excreted by the renal route via these transporters (see section 5.2).
Potential for other medicinal products to affect the pharmacokinetics of dasabuvir
Medicinal products that inhibit CYP2C8
Co-administration of dasabuvir with medicinal products that inhibit CYP2C8 (e.g. teriflunomide, deferasirox) may increase dasabuvir plasma concentrations. Strong CYP2C8 inhibitors are contraindicated with dasabuvir (see section 4.3 and Table 2).
Enzyme inducers
Co-administration of dasabuvir with medicinal products that are moderate or strong enzyme inducers is expected to decrease dasabuvir plasma concentrations and reduce its therapeutic effect. Contraindicated enzyme inducers are provided in section 4.3 and Table 2.
Dasabuvir is a substrate of P-gp and BCRP and its major metabolite M1 is a substrate of OCT1 in vitro. Inhibition of P-gp and BCRP is not expected to show clinically relevant increases in exposures of dasabuvir (Table 2).
Dasabuvir M1 metabolite was quantified in all the drug interaction studies. Changes in exposures of the metabolite were generally consistent with that observed with dasabuvir except for studies with CYP2C8 inhibitor, gemfibrozil, where the metabolite exposures decreased by up to 95% and CYP3A inducer, carbamazepine, where the metabolite exposures decreased by only up to 39%.
Drug interaction studies
Recommendations for co-administration of Exviera with ombitasvir/paritaprevir/ritonavir for a number of medicinal products are provided in Table 2.
If a patient is already taking medicinal product(s) or initiating a medicinal product while receiving Exviera and ombitasvir/paritaprevir/ritonavir for which potential for drug interaction is expected, dose adjustment of the concomitant medicinal product(s) or appropriate clinical monitoring should be considered (Table 2).
If dose adjustments of concomitant medicinal products are made due to treatment with Exviera and ombitasvir/paritaprevir/ritonavir, doses should be re-adjusted after administration of Exviera and ombitasvir/paritaprevir/ritonavir is completed.
Table 2 provides the Least Squares Means Ratio (90% Confidence Interval) effect on concentration of dasabuvir and ombitasvir/paritaprevir/ritonavir and concomitant medicinal products.
The direction of the arrow indicates the direction of the change in exposures (Cmax, and AUC) in the paritaprevir, ombitasvir, dasabuvir and the co-administered medicinal product (↑= increase more than 20%, ↓ = decrease more than 20%, ↔ = no change or change less than 20%).
This is not an exclusive list. Exviera is administered with ombitasvir/paritaprevir/ritonavir. For interactions with ombitasvir/ paritaprevir /ritonavir refer to the Summary of Product Characteristics.
Table 2. Interactions between Exviera with ombitasvir/paritaprevir/ritonavir and other medicinal products
Pregnancy
There are very limited data from the use of Exviera in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Exviera during pregnancy.
If ribavirin is co-administered with Exviera and ombitasvir/paritaprevir/ritonavir, the contraindications regarding use of ribavirin during pregnancy apply (see also the Summary of Product Characteristics of rib |
