Exviera 250 mg film-coated tablets

Each film-coated tablet contains 250 mg of dasabuvir (as sodium monohydrate).

Excipient with known effect: each film-coated tablet contains 44.94 mg lactose (as monohydrate).

For the full list of excipients, see section 6.1.

Film-coated tablet (tablet).

Beige, ovaloid, film-coated tablets with dimensions of 14.0 mm x 8.0 mm and debossed on one side with 'AV2'.

Exviera is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults (see sections 4.2, 4.4 and 5.1).

For hepatitis C virus (HCV) genotype specific activity, see sections 4.4 and 5.1.

Treatment with Exviera should be initiated and monitored by a physician experienced in the management of chronic hepatitis C.

Posology

The recommended dose of dasabuvir is 250 mg (one tablet) twice daily (morning and evening).

Exviera must not be administered as monotherapy. Exviera should be used in combination with other medicinal products for the treatment of HCV (see section 5.1). Refer to the Summary of Product Characteristics of the medicinal products that are used in combination with Exviera.

The recommended co-administered medicinal product(s) and treatment duration for Exviera combination therapy are provided in table 1.

Table 1. Recommended co-administered medicinal product(s) and treatment duration for Exviera by patient population

Missed doses

In case a dose of Exviera is missed, the prescribed dose can be taken within 6 hours. If more than 6 hours have passed since Exviera is usually taken, the missed dose should NOT be taken and the patient should take the next dose per the usual dosing schedule. Patients should be instructed not to take a double dose.

Special populations

HIV-1 Co-infection

Follow the dosing recommendations in Table 1. For dosing recommendations with HIV antiviral agents, refer to sections 4.4 and 4.5. See sections 4.8 and 5.1 for additional information.

Liver transplant recipients

Exviera and ombitasvir/paritaprevir/ritonavir in combination with ribavirin is recommended for 24 weeks in liver transplant recipients. Lower ribavirin dose at initiation may be appropriate. In the post-liver transplant study, ribavirin dosing was individualized and most subjects received 600 to 800 mg per day (see section 5.1). For dosing recommendations with calcineurin inhibitors refer to section 4.5.

Elderly

No dose adjustment of Exviera is warranted in elderly patients (see section 5.2).

Renal impairment

No dose adjustment of Exviera is required for patients with mild, moderate, or severe renal impairment (see section 5.2).

Hepatic impairment

No dose adjustment of Exviera 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 section 5.2).

Paediatric population

The safety and efficacy of dasabuvir in children less than 18 years of age have not been established. No data are available.

Method of administration

The film-coated 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).

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.