EPCLUSA

and 14 CLINICAL TRIALS). Safety and efficacy have not been studied in pediatric patients co-infected with HIV-1. The treatment of pediatric patients ≥ 12 years of age and weighing ≥ 30 kg and co -infected with HIV-1 is based on extrapolation of relevant clinical data (see 10 CLINICAL PHARMACOLOGY and 14 CLINICAL TRIALS).

1 Pediatrics (<18 years of age) The safety and efficacy of EPCLUSA in pediatric patients ≥ 12 years of age receiving EPCLUSA once daily have been established (see 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS). Exposures to EPCLUSA in pediatric patients ≥ 12 to <18 years of age and weighing ≥ 30 kg were similar to those observed in adults.

The safety and efficacy of EPCLUSA in pediatric patients < 12 years of age or weighing < 30 kg have not been established. 2 Geriatrics (≥ 65 years of age) The response rates observed for patients 65 years of age and over were similar to those of younger patients across treatment groups.

EPCLUSA can be administered in geriatric patients (see 10 CLINICAL PHARMACOLOGY and 14 CLINICAL TRIALS). 2 CONTRAINDICATIONS EPCLUSA is contraindicated in patients with known hypersensitivity to any of the components of the product.

For a complete listing, see the

and 14 CLINICAL TRIALS). Exposures to EPCLUSA in pediatric patients ≥ 12 to <18 years of age and weighing ≥ 30 kg were similar to those observed in adults. The safety and efficacy of EPCLUSA in pediatric patients < 12 years of age or weighing < 30 kg have not been established.

2 Geriatrics (≥ 65 years of age) The response rates observed for patients 65 years of age and over were similar to those of younger patients across treatment groups. EPCLUSA can be administered in geriatric patients (see 10 CLINICAL PHARMACOLOGY and 14 CLINICAL TRIALS).

2 CONTRAINDICATIONS EPCLUSA is contraindicated in patients with known hypersensitivity to any of the components of the product. For a complete listing, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the Product Monograph.

When EPCLUSA is used in combination with ribavirin, the contraindications to ribavirin are also applicable to the combination regimen. Refer to the Product Monograph containing information on ribavirin for a list of contraindications for ribavirin.

Product Monograph Epclusa (sofosbuvir/velpatasvir) tablets Page 5 of 70 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions  Potential for Hepatitis B Virus (HBV) Reactivation Screen all patients for evidence of current or prior HBV infection before initiating EPCLUSA treatment.

Cases of HBV reactivation, including those resulting in fulminant hepatitis, hepatic failure, and death, have been reported during HCV treatment and/or post -treatment with regimens containing direct acting antivirals (DAAs) in patients co-infected with HBV (see Potential for HBV Reactivation).

2 Recommended Dose and Dosage Adjustment EPCLUSA is a single tablet regimen. No dosage adjustments are possible for EPCLUSA. The recommended dose of EPCLUSA is one tablet of 400 mg/100 mg sofosbuvir/velpatasvir, taken orally, once daily with or without food (see Effects of Food).

, and 14 CLINICAL TRIALS). c . When administered w ith EPCLUSA, the recommended dose of ribavirin is based on w eight: 1000 mg per day for patients less than 75 kg and 1200 mg for those w eighing at least 75 kg, divided and administered tw ice daily w ith food.

For ribavirin dose modifications, refer to the Product Monograph containing ribavirin information. Special Populations Pediatrics (< 18 years of age) In pediatric patients ≥ 12 years of age and weighing ≥ 30 kg, the recommended dose of EPCLUSA is one 400/100 mg tablet taken orally, once daily with or without food for 12 weeks.

No dose adjustments are possible for EPCLUSA. Product Monograph Epclusa (sofosbuvir/velpatasvir) tablets Page 6 of 70 EPCLUSA is not indicated for use in pediatric patients < 12 years of age or weighing < 30 kg. Geriatrics (≥ 65 years of age) No dose adjustment is warranted for elderly patients (see 10 CLINICAL PHARMACOLOGY).

Hepatic Impairment No dose adjustment of EPCLUSA is required for adult patients with mild or moderate hepatic impairment (Child-Pugh A or B). Based on pharmacokinetic data, no dose adjustment of EPCLUSA is required for adult patients with Child-Pugh C hepatic impairment (see 10 CLINICAL PHARMACOLOGY).

However, safety and efficacy of EPCLUSA have not been established in adult patients with Child-Pugh C decompensated cirrhosis. No dose adjustment of EPCLUSA is required for pediatric patients with mild hepatic impairment (Child-Pugh A).

Safety and efficacy of EPCLUSA have not been established in pediatric patients with moderate or severe hepatic impairment (Child-Pugh B or C). Renal Impairment No dose adjustment of EPCLUSA is required for patients with any stage of renal impairment, including end stage renal disease (ESRD) requiring dialysis (see

EPCLUSA is contraindicated in patients with known hypersensitivity to any of the components of the product. For a complete listing, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the Product Monograph. When EPCLUSA is used in combination with ribavirin, the contraindications to ribavirin are also applicable to the combination regimen.

Refer to the Product Monograph containing information on ribavirin for a list of contraindications for ribavirin. Product Monograph Epclusa (sofosbuvir/velpatasvir) tablets Page 5 of 70