kirax.
HIV protease inhibitors other than atazanavir and darunavir (e.g., indinavir, saquinavir, tipranavir, lopinavir/ritonavir) are contraindicated (see section 4.3).
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 Viekirax and dasabuvir, 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 for Viekirax is required in patients with mild hepatic impairment (Child-Pugh A). The safety and efficacy of Viekirax 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.
Viekirax is contraindicated in patients with severe hepatic impairment (Child-Pugh C) (see sections 4.3 and 5.2).
HCV/HBV (Hepatitis B Virus) co-infection
The safety and efficacy of Viekirax have not been established in patients with HCV/HBV co-infection.
Paediatric population
The safety and efficacy of Viekirax in children below 18 years have not been established. No data are available.
Viekirax may be administered with or without dasabuvir. 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 increase the risk of adverse events and ALT elevations (see Table 2). Coadministration with ethinylestradiol may increase the risk of ALT elevations (see sections 4.3 and 4.4). Examples of contraindicated enzyme inducers are provided in section 4.3.
Pharmacokinetic interactions
Potential for Viekirax 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 Viekirax with or without dasabuvir. See Table 2 for guidance regarding potential interactions with other medicinal products and dosing recommendations.
Medicinal products metabolised by CYP3A4
Ritonavir is a strong inhibitor of CYP3A. Co-administration of Viekirax with or without dasabuvir with medicinal products primarily metabolized by CYP3A may result in increased plasma concentrations of these medicinal products. Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious events are contraindicated (see section 4.3 and Table 2).
CYP3A substrates eva luated in drug interaction studies which may require dose adjustment and/or clinical monitoring include (see Table 2) cyclospo
