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Sofosbuvir and Velpatasvir

Medically reviewed by Drugs.com. Last updated on Aug 3, 2020.

Pronunciation

(soe FOS bue vir & vel PAT as vir)

Index Terms

  • Velpatasvir and Sofosbuvir

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Epclusa: Sofosbuvir 400 mg and velpatasvir 100 mg

Epclusa: Sofosbuvir 200 mg and velpatasvir 50 mg [scored]

Generic: Sofosbuvir 400 mg and velpatasvir 100 mg

Brand Names: U.S.

  • Epclusa

Pharmacologic Category

  • Antihepaciviral, NS5A Inhibitor
  • Antihepaciviral, Polymerase Inhibitor (Anti-HCV)
  • NS5A Inhibitor
  • NS5B RNA Polymerase Inhibitor

Pharmacology

Velpatasvir inhibits the HCV NS5A protein necessary for viral replication; sofosbuvir is a prodrug converted to its pharmacologically active form (GS-461203), which inhibits NS5B RNA-dependent RNA polymerase, also essential for viral replication, and acts as a chain terminator.

Metabolism

Velpatasvir: Hepatic; substrate of P-gp, organic anion-transporting polypeptides (OATPs) and CYP 2B6, CYP 2C8, and CYP 3A4 (Smolders 2016)

Sofosbuvir: Hepatic; forms pharmacologically active nucleoside (uridine) analog triphosphate GS-461203; dephosphorylation results in the formation of nucleoside inactive metabolite GS-331007

Excretion

Velpatasvir: Urine: 0.4%, feces: 94%; Sofosbuvir: Urine: 80%; feces: 14%

Time to Peak

Velpatasvir: 3 hours; Sofosbuvir: 0.5 to 1 hour

Half-Life Elimination

Velpatasvir: 15 hours; Sofosbuvir: 0.5 hours

Protein Binding

Velpatasvir: >99.5%; Sofosbuvir: 61% to 65%

Special Populations: Renal Function Impairment

Sofosbuvir: Sofosbuvir AUC0-∞ was 61%, 107%, and 171% higher in subjects with mild, moderate, and severe renal impairment, while the GS-331007 AUC0-∞ was 55%, 88%, and 451% higher, respectively. In subjects with ESRD, relative to subjects with normal renal function, sofosbuvir and GS-331007 AUC0-∞ was 28% and 1,280% higher when sofosbuvir was dosed 1 hour before hemodialysis compared with 60% and 2070% higher when sofosbuvir was dosed 1 hour after hemodialysis, respectively.

Special Populations: Hepatic Function Impairment

Sofosbuvir: Sofosbuvir AUC0-24 were 126% and 143% higher in moderate and severe hepatic impairment, while the GS-331007 AUC0-24 were 18% and 9% higher, respectively. Population pharmacokinetics analysis in HCV-infected subjects indicated that cirrhosis (including decompensated cirrhosis) had no clinically relevant effect on the exposure of sofosbuvir and GS-331007.

Special Populations: Children

Sofosbuvir: In pediatric patients with severe renal impairment (including dialysis), exposure is increased to the inactive metabolite, GS-331007.

Use: Labeled Indications

Chronic hepatitis C: Treatment of chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection in adults and pediatric patients ≥6 years of age or weighing ≥17 kg without cirrhosis or with compensated cirrhosis or in combination with ribavirin in patients with decompensated cirrhosis.

Contraindications

There are no contraindications listed in the US manufacturer's labeling. If sofosbuvir/velpatasvir is administered with ribavirin, the contraindications to ribavirin also apply. See ribavirin manufacturer's labeling information.

Canadian labeling: Hypersensitivity to sofosbuvir, velpatasvir, or any component of the formulation.

Dosing: Adult

Chronic hepatitis C (HCV monoinfected or HCV/HIV co-infected): Oral:

Note: One tablet contains sofosbuvir 400 mg/velpatasvir 100 mg. Compensated cirrhosis is defined as Child-Pugh class A and decompensated cirrhosis is defined as Child-Pugh class B or C (AASLD/IDSA 2019).

Genotype 1a and 1b:

Treatment naive or peginterferon/ribavirin experienced without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

NS3 protease inhibitor + peginterferon/ribavirin experienced without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

Non-NS5A inhibitor, sofosbuvir-containing regimen experienced without cirrhosis or with compensated cirrhosis: Note: For use in genotype 1b only: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

With decompensated cirrhosis: One tablet once daily with concomitant ribavirin for 12 weeks (if ribavirin ineligible, one tablet once daily for 24 weeks) (AASLD/IDSA 2019).

Prior treatment failure with sofosbuvir- or NS5A-based regimens: One tablet once daily with concomitant ribavirin for 24 weeks (AASLD/IDSA 2019).

Post kidney transplantation, treatment-naive or nondirect-acting antiviral-experienced patients without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

Post liver transplantation:

Treatment-naive and -experienced patients without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks; in patients with compensated cirrhosis, consider adding ribavirin (AASLD/IDSA 2019).

Treatment-naive and -experienced patients with decompensated cirrhosis: One tablet once daily with concomitant ribavirin for 12 weeks (treatment naive) or 24 weeks (treatment experienced) (AASLD/IDSA 2019).

Genotype 2:

Treatment naive or peginterferon/ribavirin experienced without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

Sofosbuvir + ribavirin experienced without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

With decompensated cirrhosis: One tablet once daily with concomitant ribavirin for 12 weeks (if ribavirin-ineligible, one tablet once daily for 24 weeks) (AASLD/IDSA 2019).

Prior treatment failure with sofosbuvir- or NS5A-based regimens: One tablet once daily with concomitant ribavirin for 24 weeks (AASLD/IDSA 2019).

Post kidney transplantation, treatment-naive or nondirect-acting antiviral-experienced patients without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

Post liver transplantation:

Treatment-naive and -experienced patients without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks; in patients with compensated cirrhosis, consider adding ribavirin (AASLD/IDSA 2019).

Treatment-naive and -experienced patients with decompensated cirrhosis: One tablet once daily with concomitant ribavirin for 12 weeks (treatment naive) or 24 weeks (treatment experienced) (AASLD/IDSA 2019).

Genotype 3:

Treatment naive without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks; in patients with compensated cirrhosis with baseline NS5A resistance-associated substitution (RAS) Y93H for velpatasvir, use in combination with ribavirin or select a different regimen (AASLD/IDSA 2019).

Peginterferon/ribavirin experienced without cirrhosis: One tablet once daily for 12 weeks; in patients with baseline NS5A RAS Y93H for velpatasvir, use in combination with ribavirin or select a different regimen (AASLD/IDSA 2019).

Peginterferon/ribavirin experienced with compensated cirrhosis (alternative regimen): One tablet once daily, with concomitant ribavirin, for 12 weeks (AASLD/IDSA 2019).

With decompensated cirrhosis: One tablet once daily with concomitant ribavirin for 12 weeks (if ribavirin ineligible, one tablet once daily for 24 weeks) (AASLD/IDSA 2019).

Prior treatment failure with sofosbuvir- or NS5A-based regimens: One tablet once daily with concomitant ribavirin for 24 weeks (AASLD/IDSA 2019).

Post kidney transplantation, treatment-naive or nondirect-acting antiviral-experienced patients without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

Post liver transplantation:

Treatment-naive and -experienced patients without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks; in patients with compensated cirrhosis, consider adding ribavirin (AASLD/IDSA 2019).

Treatment-naive and -experienced patients with decompensated cirrhosis: One tablet once daily with concomitant ribavirin for 12 weeks (treatment naive) or 24 weeks (treatment experienced) (AASLD/IDSA 2019).

Genotype 4, 5, or 6:

Treatment naive or peginterferon/ribavirin experienced without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

With decompensated cirrhosis: One tablet once daily with concomitant ribavirin for 12 weeks (if ribavirin ineligible, one tablet once daily for 24 weeks) (AASLD/IDSA 2019).

Prior treatment failure with sofosbuvir- or NS5A-based regimens: One tablet once daily with concomitant ribavirin for 24 weeks (AASLD/IDSA 2019).

Post kidney transplantation, treatment-naive or nondirect-acting antiviral-experienced patients without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

Post liver transplantation:

Treatment-naive and -experienced patients without cirrhosis or with compensated cirrhosis: One tablet once daily for 12 weeks; in patients with compensated cirrhosis, consider adding ribavirin (AASLD/IDSA 2019).

Treatment-naive and -experienced patients with decompensated cirrhosis: One tablet once daily with concomitant ribavirin for 12 weeks (treatment naive) or 24 weeks (treatment experienced) (AASLD/IDSA 2019).

Hepatitis C virus-uninfected recipients of organs from hepatitis C virus-viremic donors: Oral: One tablet once daily for 12 weeks (AASLD/IDSA 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Chronic hepatitis C virus infection (monoinfected or co-infected with HIV):

Children ≥6 years weighing ≥17 kg and Adolescents:

17 to <30 kg: Oral: 200 mg sofosbuvir/50 mg velpatasvir once daily.

≥30 kg: Oral: 400 mg sofosbuvir/100 mg velpatasvir once daily.

Duration of therapy dependent upon multiple factors (eg, genotype, hepatic function [cirrhosis/compensation], previous treatment and response). Note: Treatment-experienced patients are defined as those who have failed an interferon-based regimen.

Genotype 1, 2, 3, 4, 5, or 6:

Treatment-naive or treatment-experienced patients without cirrhosis or with compensated cirrhosis (Child-Pugh class A), including patients post-liver transplantation: 12 weeks.

Treatment-naive or treatment-experienced with decompensated cirrhosis (Child-Pugh class B or C): 12 weeks in combination with ribavirin.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Oral: Administer with or without food.

Storage

Store below 30°C (86°F). Dispense in original container.

Drug Interactions

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Consider therapy modification

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Monitor therapy

Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Consider therapy modification

Amiodarone: Sofosbuvir may enhance the bradycardic effect of Amiodarone. Avoid combination

Antacids: May decrease the serum concentration of Velpatasvir. Management: Separate administration of velpatasvir and antacids by at least 4 hours. Consider therapy modification

Antidiabetic Agents: Direct Acting Antiviral Agents (HCV) may enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination

AtorvaSTATin: Velpatasvir may increase the serum concentration of AtorvaSTATin. Monitor therapy

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-gp inhibitor. Avoid concomitant use of betrixaban and P-gp inhibitors in patients with severe renal impairment (CrCL less than 30 mL/min). Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Avoid combination

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy

Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Consider therapy modification

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a P-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Consider therapy modification

CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

CYP2B6 Inducers (Moderate): May decrease the serum concentration of Velpatasvir. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Velpatasvir. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Velpatasvir. Avoid combination

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digitoxin. Monitor therapy

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Consider therapy modification

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Avoid combination

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Monitor therapy

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Avoid combination

Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Avoid combination

Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Velpatasvir. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Monitor therapy

Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Consider therapy modification

Modafinil: May decrease the serum concentration of Sofosbuvir. Avoid combination

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

OXcarbazepine: May decrease the serum concentration of Sofosbuvir. Avoid combination

Ozanimod: BCRP/ABCG2 Inhibitors may increase serum concentrations of the active metabolite(s) of Ozanimod. Avoid combination

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Sofosbuvir. Avoid combination

PHENobarbital: May decrease the serum concentration of Sofosbuvir. Avoid combination

Primidone: May decrease the serum concentration of Sofosbuvir. Avoid combination

Proton Pump Inhibitors: May decrease the serum concentration of Velpatasvir. Avoid combination

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Avoid combination

Rifabutin: May decrease the serum concentration of Sofosbuvir. Avoid combination

Rifapentine: May decrease the serum concentration of Sofosbuvir. Avoid combination

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Avoid combination

RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Monitor therapy

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Monitor therapy

Rosuvastatin: Velpatasvir may increase the serum concentration of Rosuvastatin. Management: Initiate rosuvastatin at 5 mg daily and limit the rosuvastatin dose to a maximum of 10 mg per day during coadministration with sofosbuvir/velpatasvir. Monitor closely for evidence of rosuvastatin toxicities (eg, myopathy, rhabdomyolysis). Consider therapy modification

Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Sirolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus. Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Consider therapy modification

Tacrolimus (Systemic): Sofosbuvir may decrease the serum concentration of Tacrolimus (Systemic). Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Monitor therapy

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Monitor therapy

Tenofovir Disoproxil Fumarate: Velpatasvir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Tipranavir: May decrease the serum concentration of Sofosbuvir. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tolvaptan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tolvaptan. Monitor therapy

Topotecan: Velpatasvir may increase the serum concentration of Topotecan. Avoid combination

Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Consider therapy modification

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vitamin K Antagonists (eg, warfarin): Direct Acting Antiviral Agents (HCV) may diminish the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Also see Sofosbuvir monograph.

>10%: Nervous system: Fatigue (15%), headache (22%)

1% to 10%:

Dermatologic: Skin rash (2%)

Gastrointestinal: Increased serum lipase (>3X ULN: 3% to 6%), nausea (9%)

Nervous system: Depression (1%), insomnia (5%), irritability (≥5%)

Neuromuscular & skeletal: Asthenia (5%), increased serum creatine kinase (≥10X ULN: 1% to 2%)

Postmarketing: Infection: Reactivation of HBV

ALERT: U.S. Boxed Warning

Hepatitis B virus reactivation:

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with sofosbuvir/velpatasvir. HBV reactivation has been reported in hepatitis C virus (HCV)/HBV co-infected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV co-infected 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/Precautions

Disease-related concerns:

• Diabetes: Rapid reduction in hepatitis C viral load during direct-acting antiviral (DAA) therapy for hepatitis C may lead to improvement in glucose metabolism in patients with diabetes, potentially resulting in symptomatic hypoglycemia if antidiabetic agents are continued at the same dose. Monitor for changes in glucose tolerance and inform patients of the risk of hypoglycemia during DAA therapy, particularly within the first 3 months. Modification of antidiabetic therapy may be necessary (Ciancio 2018; Dawood 2017; Hum 2017).

• Hepatitis B virus reactivation: [US Boxed Warning]: Hepatitis B virus (HBV) reactivation has been reported in hepatitis C virus (HCV)/HBV co-infected patients who were receiving or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy; some cases have resulted in fulminant hepatitis, hepatic failure, and death. Test all patients for evidence of current or prior HBV infection prior to initiation of ledipasvir/sofosbuvir; monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Initiate treatment for HBV infection as clinically indicated. HBV reactivation has been reported in HBsAg positive patients and in patients with serologic evidence of resolved HBV infection (ie, HBsAg negative and anti-HBc positive) and is characterized by an abrupt increase in HBV replication manifested as a rapid increase in serum HBV DNA level; reappearance of HBsAg may occur in patients with resolved HBV infection. Risk of HBV reactivation may be increased in patients receiving certain immunosuppressants or chemotherapeutic agents.

Concurrent drug therapy issues:

• Amiodarone: Symptomatic bradycardia (some requiring pacemaker intervention) has occurred in patients receiving amiodarone and a sofosbuvir-containing regimen. A fatal cardiac arrest was reported in a patient taking amiodarone with sofosbuvir/ledipasvir. Bradycardia generally occurred within hours to days following coadministration; however, some cases have occurred 2 weeks following the initiation of HCV treatment. The risk of bradycardia may be increased in patients taking beta blockers or patients with underlying cardiac comorbidities and/or advanced liver disease. Bradycardia generally resolves following discontinuation. Coadministration of amiodarone and sofosbuvir/velpatasvir is not recommended. However, if patients have no treatment alternatives, patients should have inpatient cardiac monitoring for the first 48 hours, followed by daily outpatient or self-monitoring of heart rate for at least the first 2 weeks of treatment. Due to the long half-life of amiodarone, cardiac monitoring (as described) is also recommended if amiodarone was discontinued just prior to beginning treatment with velpatasvir/sofosbuvir. Patients should seek medical attention immediately if they experience fainting or near-fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion or memory problems.

Monitoring Parameters

Baseline (within 6 months prior to starting direct-acting antiviral [DAA] therapy) CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), and calculated GFR; repeat hepatic function panel as clinically indicated. Baseline (at any time prior to starting therapy) quantitative hepatitis C virus (HCV) viral load and HCV genotype and subtype (if nonpan-genotypic DAA will be prescribed); repeat quantitative HCV viral load testing ≥12 weeks after completion of therapy. If quantitative HCV viral load is detectable at treatment week 4, repeat testing is recommended after 2 additional weeks of treatment (treatment week 6). Presence of HIV coinfection prior to initiation of therapy (AASLD/IDSA 2019). Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) prior to initiation; in patients with serologic evidence of hepatitis B virus (HBV) infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during treatment and during posttreatment follow-up.

In patients with diabetes, monitor blood glucose and for signs/symptoms of hypoglycemia (Ciancio 2018; Dawood 2017; Hum 2017).

If used in combination with amiodarone (or in patients who discontinued amiodarone just prior to initiating sofosbuvir/velpatasvir), inpatient cardiac monitoring for the first 48 hours of coadministration, then outpatient or self-monitoring of heart rate daily through at least the first 2 weeks of treatment.

Reproductive Considerations

HCV-infected females of childbearing potential should consider postponing pregnancy until therapy is complete to reduce the risk of HCV transmission (AASLD/IDSA 2018).

If used in combination with ribavirin, all warnings related to the use of ribavirin and contraception should be followed. Refer to the ribavirin monograph for additional information.

Pregnancy Considerations

Use in combination with ribavirin is contraindicated in pregnancy. If used in combination with ribavirin, all warnings related to the use of ribavirin and pregnancy should be followed. Refer to the ribavirin monograph for additional information.

Treatment of hepatitis C is not currently recommended to treat maternal infection or to decrease the risk of mother-to-child transmission during pregnancy (Tran 2016). When HCV infection is detected during pregnancy, treatment should be deferred until after delivery. Direct-acting antiviral medications should not be used in pregnant females outside of clinical trials until safety and efficacy information is available (SMFM [Hughes 2017]).

Patient Education

What is this drug used for?

• It is used to treat hepatitis C infection.

• This drug may be used with ribavirin. If you are also taking ribavirin, talk with the doctor about the risks and side effects that may happen.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling tired or weak

• Headache

• Upset stomach

• Diarrhea

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions