A WELL-ESTABLISHED SAFETY PROFILE¹

See BOXED WARNING for
Risk of Hepatitis B Reactivation

See Warnings and Precautions

ESTABLISHED DDI PROFILE FOR PEOPLE WITH CHRONIC HEP C^1,2

Only EPCLUSA has

No clinically significant drug interactions with¹:

Ethinyl estradiol/norgestimate-based birth control^a

^aAmong first-line pangenotypic regimens.

EPCLUSA HAS NO INTERACTIONS
EXPECTED WITH²:

Antipsychotics

ABILIFY (aripiprazole)
SEROQUEL (quetiapine)

Opioids

Fentanyl
Oxycodone

Additional Information on EPCLUSA Drug Interactions¹

Coadministration of EPCLUSA is not recommended with:

Antiarrhythmics

Amiodarone, due to the risk of symptomatic bradycardia

P-gp inducers and/or moderate to strong inducers of CYP2B6, CYP2C8, or CYP3A4

May significantly decrease plasma concentrations of sofosbuvir and/or velpatasvir, leading to reduced therapeutic effect of EPCLUSA

Certain other medications

Omeprazole/other PPIs, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir, due to decreased concentration of sofosbuvir and/or velpatasvir
- If medically necessary, EPCLUSA should be administered with food and taken 4 hours before omeprazole 20 mg. Use with other PPIs has not been studied

Other considerations:

Additional monitoring/dosing adjustments may be required with rosuvastatin or atorvastatin, as they may be associated with an increased risk of myopathy, including rhabdomyolysis
Clearance of HCV infection with DAAs may alter hepatic function, impacting safe and effective use of concomitant medications. Frequent monitoring of relevant laboratory parameters and dose adjustments of certain concomitant medications may be necessary. See the EPCLUSA full Prescribing Information for a detailed list of additional drugs with no known interactions and other coadministration recommendations

MOST COMMON ADVERSE REACTIONS IN THE SIMPLIFY STUDY¹

Adverse Reactions	SIMPLIFY Study (n=103)
Fatigue	18%
Nausea	13%
Headache	11%

The adverse reactions observed from SIMPLIFY both overall and in subjects on MOUD were consistent with the known safety profile of EPCLUSA
Adverse reactions leading to permanent discontinuation of treatment were not observed in any subjects

DRUG INTERACTIONS¹

Clearance of hepatitis C virus infection with direct-acting antivirals may lead to changes in hepatic function, which may impact safe and effective use of concomitant medications. Frequent monitoring of relevant laboratory parameters (eg, INR in patients taking warfarin and blood glucose levels in diabetic patients) and dose adjustments of certain concomitant medications may be necessary.

Potentially significant drug interactions: Alteration in dose or regimen may be recommended based on drug interaction studies or predicted interaction^1,b

Concomitant Drug Class	Effect on Concentration^c	Clinical Effect/Recommendation
Acid-reducing agents		Velpatasvir solubility decreases as pH increases. Drugs that increase gastric pH are expected to decrease concentration of velpatasvir.
antacids (eg, aluminum and magnesium hydroxide)	velpatasvir	Separate antacid and EPCLUSA administration by 4 hours.
H₂-receptor antagonists^d (eg, famotidine)	velpatasvir	H₂-receptor antagonists may be administered simultaneously with or 12 hours apart from EPCLUSA at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.
proton-pump inhibitors^d (eg, omeprazole)	velpatasvir	Coadministration of omeprazole or other proton-pump inhibitors is not recommended. If it is considered medically necessary to coadminister, EPCLUSA should be administered with food and taken 4 hours before omeprazole 20 mg. Use with other proton-pump inhibitors has not been studied.
Antiarrhythmics
amiodarone	Effect on amiodarone, sofosbuvir, and velpatasvir concentrations unknown	Coadministration of amiodarone with a sofosbuvir-containing regimen may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with EPCLUSA is not recommended; if coadministration is required, cardiac monitoring is recommended.
digoxin^d	digoxin	Therapeutic concentration monitoring of digoxin is recommended when coadministered with EPCLUSA. Refer to digoxin Prescribing Information for monitoring and dose modification recommendations for concentration increases of less than 50%.
Anticancers
topotecan	topotecan	Coadministration is not recommended.
Anticonvulsants
carbamazepine^d, phenytoin, phenobarbital	sofosbuvir velpatasvir	Coadministration is not recommended.
Antimycobacterials
rifabutin^d, rifampin^d, rifapentine	sofosbuvir velpatasvir	Coadministration is not recommended.
HIV antiretrovirals
efavirenz^d	velpatasvir	Coadministration of EPCLUSA with efavirenz-containing regimens is not recommended.
regimens containing tenofovir DF	tenofovir	Monitor for tenofovir-associated adverse reactions in patients receiving EPCLUSA concomitantly with a regimen containing tenofovir DF. Refer to the Prescribing Information of the tenofovir DF-containing product for recommendations on renal monitoring.
tipranavir/ritonavir	sofosbuvir velpatasvir	Coadministration is not recommended.
Herbal supplements
St. John’s wort (Hypericum perforatum)	sofosbuvir velpatasvir	Coadministration is not recommended.
HMG-CoA reductase inhibitors
rosuvastatin^d	rosuvastatin	Coadministration of EPCLUSA with rosuvastatin may significantly increase the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis. Rosuvastatin may be administered with EPCLUSA at a dose that does not exceed 10 mg.
atorvastatin^d	atorvastatin	Coadministration of EPCLUSA with atorvastatin may be associated with increased risk of myopathy, including rhabdomyolysis. Monitor closely for HMG-CoA reductase inhibitor-associated adverse reactions, such as myopathy and rhabdomyolysis.

HMG CoA reductase inhibitors mobile icon

^b This table is not all inclusive.¹

^c = decrease, = increase.¹

^d These interactions have been studied in healthy adults.¹

No clinically significant interactions between velpatasvir and pravastatin. Interactions between sofosbuvir and pravastatin have not been studied¹
No clinically significant interactions with MOUD such as buprenorphine/naloxone, methadone, or naltrexone¹

Consult the full Prescribing Information for EPCLUSA (sofosbuvir/velpatasvir) for more information on potentially significant drug interactions, including clinical comments.

Please see the full Prescribing Information or Package Insert for EPCLUSA.

ADVERSE REACTIONS (ALL GRADES) REPORTED IN ≥5% OF SUBJECTS TREATED WITH EPCLUSA IN ASTRAL-1^1,3

ASTRAL-1 Study (12 weeks)^1,3

Adverse Reactions	EPCLUSA (n=624)	Placebo (n=116)
Headache	22%	28%
Fatigue	15%	20%
Nausea	9%	11%
Insomnia	5%	9%
Asthenia	5%	8%

The majority of these adverse reactions in ASTRAL‑1 were of mild severity (Grade 1, 79%)¹
The adverse reactions observed in subjects treated with EPCLUSA in ASTRAL‑2 and ASTRAL‑3 were consistent with those observed in ASTRAL‑1¹
Irritability was also observed in ≥5% of subjects treated with EPCLUSA in ASTRAL‑3¹

Discontinuation rates evaluated across ASTRAL-1, -2, and -3¹

0.2% discontinuation rate due to AEs (n=2/1035; Pivotal Studies)¹

INDICATION

EPCLUSA (sofosbuvir 400 mg/velpatasvir 100 mg, 200 mg/50 mg tablets; 200 mg/50 mg, 150 mg/37.5 mg oral pellets) is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic hepatitis C virus (HCV) genotype 1-6 infection without cirrhosis or with compensated cirrhosis.

Important Safety Information

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.

Warnings and Precautions

Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with EPCLUSA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/ or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir- containing regimen. In patients without alternative viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.

Risk of Reduced Therapeutic Effect Due to Concomitant Use of EPCLUSA with P-gp Inducers and/or Moderate to Strong Inducers of CYP2B6, CYP2C8 or CYP3A4: Rifampin, St. John’s wort, and carbamazepine are not recommended for use with EPCLUSA as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations.

Adverse Reactions

The most common adverse reactions (≥10%, all grades) with EPCLUSA in adults and pediatric patients 6 years of age and older were headache and fatigue. The most common adverse reactions (≥10%, grade 1 or 2) for pediatric patients less than 6 years of age were vomiting and spitting up the drug.

Drug Interactions

Coadministration of EPCLUSA is not recommended with topotecan due to increased concentrations of topotecan.

Coadministration of EPCLUSA is not recommended with proton-pump inhibitors, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir.

Consult the full Prescribing Information for EPCLUSA for more information on potentially significant drug interactions, including clinical comments.

Please see full Prescribing Information for EPCLUSA, including BOXED WARNING on hepatitis B reactivation.

A WELL-ESTABLISHED SAFETY PROFILE1

ESTABLISHED DDI PROFILE FOR PEOPLE WITH CHRONIC HEP C1,2

Only EPCLUSA has

Additional Information on EPCLUSA Drug Interactions1

MOST COMMON ADVERSE REACTIONS IN THE SIMPLIFY STUDY1

DRUG INTERACTIONS1

Potentially significant drug interactions: Alteration in dose or regimen may be recommended based on drug interaction studies or predicted interaction1,b

ADVERSE REACTIONS (ALL GRADES) REPORTED IN ≥5% OF SUBJECTS TREATED WITH EPCLUSA IN ASTRAL-11,3

ASTRAL-1 Study (12 weeks)1,3

Discontinuation rates evaluated across ASTRAL-1, -2, and -31

0.2% discontinuation rate due to AEs (n=2/1035; Pivotal Studies)1

A WELL-ESTABLISHED SAFETY PROFILE¹

ESTABLISHED DDI PROFILE FOR PEOPLE WITH CHRONIC HEP C^1,2

Additional Information on EPCLUSA Drug Interactions¹

MOST COMMON ADVERSE REACTIONS IN THE SIMPLIFY STUDY¹

DRUG INTERACTIONS¹

Potentially significant drug interactions: Alteration in dose or regimen may be recommended based on drug interaction studies or predicted interaction^1,b

ADVERSE REACTIONS (ALL GRADES) REPORTED IN ≥5% OF SUBJECTS TREATED WITH EPCLUSA IN ASTRAL-1^1,3

ASTRAL-1 Study (12 weeks)^1,3

Discontinuation rates evaluated across ASTRAL-1, -2, and -3¹

0.2% discontinuation rate due to AEs (n=2/1035; Pivotal Studies)¹