ted tablets are for oral use. Patients should be instructed to swallow the tablets whole (i.e. patients should not chew, break or dissolve the tablet). To maximise absorption, Exviera tablets should be taken with food, without regard to fat and calorie content (see section 5.2).
4.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
Use of ethinylestradiol-containing medicinal products such as those contained in most combined oral contraceptives or contraceptive vaginal rings (see section 4.4 and 4.5).
Co-administration of Exviera with medicinal products that are strong or moderate enzyme inducers is expected to decrease dasabuvir plasma concentrations and reduce its therapeutic effect (see section 4.5. Examples of contraindicated inducers are provided below.
Enzyme inducers:
• carbamazepine, phenytoin, phenobarbital
• efavirenz, nevirapine, etravirine
• enzalutamide
• mitotane
• rifampicin
• St. John's Wort (Hypericum perforatum)
Medicinal products that are strong CYP2C8 inhibitors may increase dasabuvir plasma concentrations and must not be co-administered with Exviera (see section 4.5). Examples of contraindicated CYP2C8 inhibitors are provided below.
CYP2C8 inhibitor:
• gemfibrozil
Exviera is administered with ombitasvir/ paritaprevir /ritonavir. For contra-indications with ombitasvir/ paritaprevir /ritonavir refer to the Summary of Product Characteristics.
4.4 Special warnings and precautions for use
General
Exviera is not recommended for administration as monotherapy and must be used in combination with other medicinal products for the treatment of hepatitis C infection (see section 4.2 and 5.1).
Genotype-specific activity
Concerning recommended regimens with different HCV genotypes, see section 4.2. Concerning genotype-specific virological and clinical activity, see section 5.1.
The efficacy of dasabuvir has not been established in patients with HCV genotypes other than genotype 1; Exviera should not be used for the treatment of patients infected with other genotypes than 1.
Co-administration with other direct-acting antivirals against HCV
Exviera safety and efficacy have been established in combination with ombitasvir/ paritaprevir /ritonavir with or without ribavirin. Co-administration of Exviera with other antivirals has not been studied and, therefore, cannot be recommended.
Retreatment
The efficacy of dasabuvir in patients previously exposed to dasabuvir, or to medicinal products anticipated to be cross-resistant, has not been demonstrated.
Pregnancy and concomitant use with ribavirin
When dasabuvir is used in combination with ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and for 6 months after the treatment as recommended in the Summary of Product Characteristics for ribavirin. Refer to the Summary of Product Characteristics for ribavirin for additional information.
ALT elevations
During clinical trials with dasabuvir and ombitasvir/paritaprevir/ritonavir with or without ribavirin, transient elevations of ALT to greater than 5 times the upper limit of normal occurred in approximately 1% of subjects (35 of 3,039). ALT elevations were asymptomatic and generally occurred during the first 4 weeks of treatment, without concomitant elevations of bilirubin, an |
