administered at the same time as ombitasvir/paritaprevir/ritonavir, can be used in the absence of extensive PI resistance (darunavir exposure lowered). To be noted, darunavir should be taken without ritonavir, since ritonavir 100 mg once daily is provided as part of the ombitasvir/paritaprevir/ritonavir fixed dose combination.
For the use of HIV protease inhibitors other than atazanavir and darunavir refer to the Summary of Product Characteristics of ombitasvir/ paritaprevir /ritonavir.
Raltegravir exposure is substantially increased (2-fold). The combination was not linked to any particular safety issues in a limited set of patients treated for 12-24 weeks.
Rilpivirine exposure is substantially increased (3-fold) when rilpivirine is given in combination with dasabuvir with ombitasvir/paritaprevir/ritonavir, with a consequent potential for QT-prolongation. If an HIV protease inhibitor is added (atazanavir, darunavir), rilpivirine exposure may increase even further and is therefore not recommended. Rilpivirine should be used cautiously, in the setting of repeated ECG monitoring.
NNRTIs other than rilpivirine (efavirenz, etravirine, and nevirapine) are contraindicated (see section 4.3).
Hepatic impairment
No dose adjustment of Exviera and ombitasvir/paritaprevir/ritonavir is required in patients with mild hepatic impairment (Child-Pugh A). The safety and efficacy of dasabuvir have not been established in HCV-infected patients with moderate hepatic impairment (Child-Pugh B); however, no dose adjustment is expected to be required based on pharmacokinetic studies.
Exviera should not be used in patients with severe hepatic impairment (Child Pugh C) (see sections 4.2 and 5.1).
HCV/HBV (Hepatitis B Virus) co-infection
The safety and efficacy of dasabuvir have not been established in patients with HCV/HBV co-infection.
Paediatric population
The safety and efficacy of dasabuvir in children below 18 years have not been established. No data are available.
Lactose
Exviera contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
4.5 Interaction with other medicinal products and other forms of interaction
Dasabuvir must always be administered together with ombitasvir/paritaprevir/ritonavir . When co-administered they exert mutual effects on each other (see section 5.2). Therefore, the interaction profile of the compounds must be considered as a combination.
Pharmacodynamic interactions
Coadministration with enzyme inducers may lead to an increased risk of adverse reactions and ALT elevations (see Table 2).
Coadministration with ethinylestradiol may lead to increased risk of ALT elevations (see sections 4.3 and 4.4). Contraindicated enzyme inducers are provided in section 4.3.
Pharmacokinetic interactions
Potential for Exviera to affect the pharmacokinetics of other medicinal products
In vivo drug interaction studies eva luated the net effect of the combination treatment, including ritonavir. The following section describes the specific transporters and metabolizing enzymes that are affected by dasabuvir when combined with ombitasvir/paritaprevir/ritonavir. See Table 2 for guidance regarding potential drug interactions and dosing recommendations for Exviera administered with ombitasvir/paritaprevir/ritonavir.
Medicinal products metabolis |
