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Sofosbuvir and velpatasvir: Drug information

Sofosbuvir and velpatasvir: Drug information
(For additional information see "Sofosbuvir and velpatasvir: Patient drug information" and see "Sofosbuvir and velpatasvir: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US 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.

Brand Names: US
  • Epclusa
Brand Names: Canada
  • Epclusa
Pharmacologic Category
  • Antihepaciviral, NS5A Inhibitor;
  • Antihepaciviral, Polymerase Inhibitor (Anti-HCV);
  • NS5A Inhibitor;
  • NS5B RNA Polymerase Inhibitor
Dosing: Adult
Chronic hepatitis C, treatment

Chronic hepatitis C, treatment: Oral:

Note: 1 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 (Ref).

Treatment naive without cirrhosis or with compensated cirrhosis, genotypes 1, 2, 3, 4, 5, or 6:

Note: Genotype 3 patients with compensated cirrhosis should be tested for NS5A–resistant-associated substitution (RAS) Y93H for velpatasvir; if present, use sofosbuvir and velpatasvir in combination with ribavirin or select a different regimen (Ref).

Oral: 1 tablet once daily for 12 weeks (Ref).

Decompensated cirrhosis, genotypes 1, 2, 3, 4, 5, or 6: Oral: 1 tablet once daily in combination with concomitant ribavirin for 12 weeks; if ribavirin ineligible, 1 tablet once daily for 24 weeks (Ref).

Decompensated cirrhosis, with prior sofosbuvir or NS5A inhibitor-based treatment failure, genotypes 1, 2, 3, 4, 5, or 6: Oral: 1 tablet once daily in combination with concomitant ribavirin for 24 weeks (Ref).

Post kidney transplant, genotypes 1, 2, 3, 4, 5, or 6:

Treatment naive and nondirect-acting antiviral-experienced, without cirrhosis or with compensated cirrhosis: Oral: 1 tablet once daily for 12 weeks (Ref).

Post liver transplant, genotypes 1, 2, 3, 4, 5, or 6:

Treatment naive and nondirect-acting antiviral-experienced, without cirrhosis or with compensated cirrhosis: Oral: 1 tablet once daily for 12 weeks (Ref).

Decompensated cirrhosis: Oral: 1 tablet once daily in combination with concomitant ribavirin for 12 weeks (treatment naive) or 24 weeks (nondirect acting antiviral treatment-experienced) (Ref).

Hepatitis C virus–uninfected recipients of organs from hepatitis C virus–viremic donors

Hepatitis C virus–uninfected recipients of organs from hepatitis C virus–viremic donors (off-label use): Oral: 1 tablet once daily for 12 weeks (Ref).

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

Dosing: Kidney Impairment: Adult

Mild, moderate, or severe impairment: No dosage adjustment necessary.

End-stage renal disease requiring hemodialysis: No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Preexisting hepatic impairment: Mild, moderate, or severe impairment (Child-Pugh class A, B, or C): No dosage adjustment necessary.

Hepatotoxicity during treatment:

Asymptomatic increases in ALT <10-fold: Closely monitor with repeat testing every 2 weeks. If persistent elevation remains, consider stopping therapy (Ref).

<10-fold increase in ALT from baseline with weakness, nausea, vomiting, jaundice, or significantly increased bilirubin, alkaline phosphatase, or INR: Discontinue direct-acting antiviral (Ref).

≥10-fold increase in ALT from baseline at any time during treatment: Discontinue direct-acting antiviral therapy, especially with signs and symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR (Ref).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Sofosbuvir and velpatasvir: Pediatric drug information")

Chronic hepatitis C

Chronic hepatitis C:

Children ≥3 years and Adolescents:

<17 kg: Oral pellets: Oral: Sofosbuvir 150 mg/velpatasvir 37.5 mg once daily.

17 to <30 kg: Oral pellets, tablet: Oral: Sofosbuvir 200 mg/velpatasvir 50 mg once daily.

≥30 kg: Oral pellets, tablet: Oral: Sofosbuvir 400 mg/velpatasvir 100 mg 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 patients 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.

Dosing: Kidney Impairment: Pediatric

Children ≥3 years and Adolescents:

Mild, moderate, or severe impairment: No dosage adjustment necessary.

End-stage renal disease requiring hemodialysis: No dosage adjustment necessary.

Note: Safety data in pediatric patients with renal impairment unavailable.

Dosing: Hepatic Impairment: Pediatric

Children ≥3 years and Adolescents: Mild, moderate, or severe impairment: No dosage adjustment necessary.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see Sofosbuvir.

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

1% to 10%:

Cardiovascular: Increased serum creatine kinase (≥10X ULN: 1% to 2%)

Dermatologic: Skin rash (2%)

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

Nervous system: Asthenia (5%), depressed mood (1%), insomnia (5%), irritability (≥5%)

Postmarketing: Infection: Reactivation of HBV (including fulminant hepatitis and hepatic failure)

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.

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.

Warnings: Additional Pediatric Considerations

Mild GI adverse effects associated with sofosbuvir/velpatasvir are more common in patients 3 to <6 years of age compared to those ≥6 years of age. Vomiting was reported in 15% and spitting up the drug was reported in 10% of study subjects 3 to <6 years of age, leading to discontinuation in 12% of the study population.

Dosage Forms: US

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

Packet, Oral:

Epclusa: Sofosbuvir 200 mg and velpatasvir 50 mg (1 ea, 28 ea); Sofosbuvir 150 mg and velpatasvir 37.5 mg (1 ea, 28 ea)

Tablet, Oral:

Epclusa: Sofosbuvir 200 mg and velpatasvir 50 mg, Sofosbuvir 400 mg and velpatasvir 100 mg

Generic: Sofosbuvir 400 mg and velpatasvir 100 mg

Generic Equivalent Available: US

May be product dependent

Pricing: US

Pack (Epclusa Oral)

150-37.5 mg (per each): $1,068.00

200-50 mg (per each): $1,068.00

Tablets (Epclusa Oral)

200-50 mg (per each): $1,068.00

400-100 mg (per each): $1,068.00

Tablets (Sofosbuvir-Velpatasvir Oral)

400-100 mg (per each): $342.86

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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

Tablet, Oral:

Epclusa: Sofosbuvir 400 mg and velpatasvir 100 mg

Administration: Adult

Oral: Administer with or without food.

Administration: Pediatric

Oral: May be administered with or without food.

Oral pellets: Administration with food is recommended for patients 3 to <6 years of age to improve palatability.

If administering by mouth: Pour contents of packet into mouth and swallow; do not chew due to bitter aftertaste. Water may be administered after oral pellets.

If administering with food: Pour a small amount (≥1 spoonfuls) of nonacidic soft food (eg, pudding, chocolate syrup, ice cream) into a bowl; food should be at room temperature or colder. Sprinkle oral pellets over food and gently mix; administer entire mixture within 15 minutes of mixing and swallow contents without chewing to avoid bitter taste. Ensure entire dose is consumed; do not store or try to reuse the sofosbuvir/velpatasvir and food mixture.

Use: Labeled Indications

Hepatitis C, chronic, treatment: Treatment of chronic hepatitis C virus genotypes 1, 2, 3, 4, 5, or 6 infection in adults and pediatric patients ≥3 years of age without cirrhosis or with compensated cirrhosis or in combination with ribavirin in patients with decompensated cirrhosis.

Use: Off-Label: Adult

Hepatitis C virus–uninfected recipients of organs from hepatitis C virus–viremic donors

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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. Risk D: Consider therapy modification

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: 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. Risk D: Consider therapy modification

Amiodarone: Sofosbuvir may enhance the bradycardic effect of Amiodarone. Management: Use alternative to a sofosbuvir-containing combo or to amiodarone when possible. If alternatives not possible, monitor in inpatient setting for first 48 hours of coadministration with daily outpatient monitoring for at least 2 weeks. Risk D: Consider therapy modification

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

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

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

Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider therapy modification

Atorvastatin: Velpatasvir may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy

Atorvastatin: Sofosbuvir may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy

Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification

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

Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: 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. Risk D: 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: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification

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

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

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

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

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: 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. Risk D: Consider therapy modification

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

DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy

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

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

Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: 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. Risk D: Consider therapy modification

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

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

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

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

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

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Velpatasvir. Management: Sofosbuvir/velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Sofosbuvir/velpatasvir/voxilaprevir can be administered with omeprazole 20 mg. Use with other PPIs or PCABs has not been studied. Risk D: Consider therapy modification

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

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: 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. Risk D: Consider therapy modification

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

Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification

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

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

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification

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

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

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

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

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

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification

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

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: 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). Risk D: Consider therapy modification

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

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

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). 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. Risk D: Consider therapy modification

Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

Tacrolimus (Systemic): Direct Acting Antiviral Agents (HCV) may decrease the serum concentration of Tacrolimus (Systemic). Direct Acting Antiviral Agents (HCV) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

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

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

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

Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy

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

Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy

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

Topotecan: Velpatasvir may increase the serum concentration of Topotecan. Risk X: 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. Risk D: 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. Risk D: Consider therapy modification

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

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

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

Reproductive Considerations

Patients with hepatitis C virus (HCV) infection should be treated before considering pregnancy to optimize maternal health and reduce the risk of HCV transmission (AASLD/IDSA 2021).

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 during 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.

Outcome data following maternal use of direct-acting antiviral (DAA) medications during pregnancy are limited. Use of a DAA is not currently recommended for the purpose of reducing mother to child transmission of hepatitis C virus due to a lack of safety and efficacy data. The decision to continue treatment in a patient who becomes pregnant while taking a DAA should be individualized after considering the potential benefits and risks of therapy. DAA medications should not be initiated during pregnancy outside of clinical trials until safety and efficacy data are available (AASLD/IDSA 2021; SMFM [Dotters-Katz 2021]).

Breastfeeding Considerations

It is not known if sofosbuvir or velpatasvir are present in breast milk.

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Breastfeeding is not linked to the spread of hepatitis C virus; however, if nipples are cracked or bleeding, breastfeeding is not recommended (milk should be expressed and discarded) (AASLD/IDSA 2021; SMFM [Dotters-Katz 2021]).

Monitoring Parameters

Pretreatment assessment: Evaluate for advanced hepatic fibrosis and hepatocellular carcinoma. Confirm vaccination against hepatitis A and B (AASLD/IDSA 2021). Assess for potential drug-drug interactions and patient's readiness for adherence.

Laboratory tests recommended at any time before starting therapy:

Quantitative hepatitis C virus (HCV) RNA (HCV viral load), HIV antigen/antibody (AASLD/IDSA 2021).

Assessment for active hepatitis B virus coinfection: Hepatitis B virus (HBV) surface antigen (HBsAg); HBV core antibody (anti-HBc) and HBV surface antibody (anti-HBs); if evidence of hepatitis B viral coinfection, HBV DNA level should be drawn. HBsAg-positive patients not already receiving HBV suppressive therapy should be either: initiated on prophylactic HBV antiviral therapy (for those with low or undetectable HBV DNA levels), which should be continued until 12 weeks after completion of HCV therapy, OR monitor HBV DNA levels monthly during and immediately after HCV therapy (AASLD/IDSA 2021).

Laboratory tests recommended 6 months prior to starting therapy: CBC, INR, hepatic function panel (serum albumin, total and direct bilirubin, ALT, AST, alkaline phosphatase), eGFR (AASLD/IDSA 2021).

Laboratory tests immediately prior to starting therapy:

Serum pregnancy test for patients of childbearing potential.

Patients with genotype 3 require baseline NS5A resistance-associated substation testing for Y93H (AASLD/IDSA 2021).

On-treatment monitoring:

Periodic monitoring of LFTs and assessment for presence of symptoms of liver dysfunction (eg, weakness, nausea, vomiting, jaundice, or significantly elevated bilirubin, alkaline phosphatase, or INR) (AASLD/IDSA 2021).

In patients with diabetes, monitor blood glucose and for signs/symptoms of hypoglycemia (AASLD/IDSA 2020; Ciancio 2018; Dawood 2017; Hum 2017); in patients taking warfarin, monitor INR during and post therapy (AASLD/IDSA 2021).

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.

Post treatment assessment of cure: Quantitative HCV viral load testing 12 or more weeks after completion of therapy to document sustained virologic response and liver transaminases (AASLD/IDSA 2021).

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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

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

Half-life elimination: Velpatasvir: 15 hours; Sofosbuvir: 0.5 hours

Time to peak: Velpatasvir: 3 hours; Sofosbuvir: 0.5 to 1 hour

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

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: 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.

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.

Pediatric: Sofosbuvir exposure, as measured by AUC and Cmax, was higher in pediatric patients as compared to adults. Exposure in patients <17 kg was the highest, followed by patients 17 to <30 kg and patients ≥30 kg; differences were not considered clinically significant. Exposures of sofosbuvir metabolite GS-331007 and velpatasvir were similar to adults.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Epclusa;
  • (AR) Argentina: Epclusa;
  • (AT) Austria: Epclusa;
  • (BD) Bangladesh: Panovir | Sofosvel;
  • (BE) Belgium: Epclusa;
  • (BG) Bulgaria: Epclusa;
  • (BR) Brazil: Epclusa;
  • (CH) Switzerland: Epclusa;
  • (CL) Chile: Epclusa;
  • (CN) China: Epclusa | Sofosbuvir and velpatasvir;
  • (CO) Colombia: Epclusa;
  • (CZ) Czech Republic: Epclusa;
  • (DE) Germany: Epclusa;
  • (EE) Estonia: Epclusa;
  • (EG) Egypt: Nucleobuvir velpa | Sovelpak;
  • (ES) Spain: Epclusa;
  • (ET) Ethiopia: Epclusa;
  • (FI) Finland: Epclusa;
  • (FR) France: Epclusa;
  • (GB) United Kingdom: Epclusa;
  • (GR) Greece: Epclusa;
  • (HK) Hong Kong: Epclusa;
  • (HR) Croatia: Epclusa;
  • (HU) Hungary: Epclusa;
  • (IE) Ireland: Epclusa;
  • (IN) India: Hepcvel | Myhep all | Resof total | Sovihep v | Velasof | Velpaclear | Velpanat | Velpas s;
  • (IQ) Iraq: Cluza c;
  • (IT) Italy: Epclusa;
  • (JP) Japan: Epclusa;
  • (KE) Kenya: Myhep all;
  • (KW) Kuwait: Epclusa;
  • (LT) Lithuania: Myhep all | Velpanat;
  • (LV) Latvia: Epclusa;
  • (MA) Morocco: Epclusa | Myhep all;
  • (MX) Mexico: Epclusa;
  • (MY) Malaysia: Epclusa | Myhep all;
  • (NG) Nigeria: Myhep all;
  • (NL) Netherlands: Epclusa;
  • (NO) Norway: Epclusa;
  • (PE) Peru: Epclusa;
  • (PH) Philippines: Epclusa;
  • (PK) Pakistan: Abriva plus | Chc plus | Dowvir | Epclusa | Fosbu v | Hepgard v | Hilvel | Maclusa | Myhep all | Ocvir v | Sepavir | Sofvel | Sovela | Sovelpa | Velpaget | Velscot | Velso | Velsovir | Vibrenta vpt | Viktana;
  • (PL) Poland: Epclusa;
  • (PR) Puerto Rico: Epclusa | Sofosbuvir and velpatasvir;
  • (PT) Portugal: Epclusa;
  • (RO) Romania: Epclusa;
  • (RU) Russian Federation: Epclusa;
  • (SA) Saudi Arabia: Epclusa;
  • (SE) Sweden: Epclusa;
  • (SG) Singapore: Epclusa;
  • (SI) Slovenia: Epclusa;
  • (TH) Thailand: Myhep all;
  • (TW) Taiwan: Epclusa;
  • (UA) Ukraine: Myhep all | Velpanat;
  • (UG) Uganda: Epclusa;
  • (VN) Viet Nam: Velakast
  1. American Association for the Study of Liver Diseases (AASLD), Infectious Diseases Society of America (IDSA). HCV guidance: recommendations for testing, managing, and treating hepatitis C. https://www.hcvguidelines.org/. Updated October 5, 2021. Accessed March 28, 2022.
  2. American Association for the Study of Liver Diseases (AASLD), Infectious Diseases Society of America (IDSA). HCV in children. https://www.hcvguidelines.org/unique-populations/children. Updated December 10, 2019. Accessed April 16, 2020.
  3. American Association for the Study of Liver Diseases (AASLD), Infectious Diseases Society of America (IDSA). HCV resistance primer. https://www.hcvguidelines.org/evaluate/resistance. Accessed March 28, 2022.
  4. Ciancio A, Bosio R, Bo S, et al. Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents. J Med Virol. 2018;90(2):320-327. doi:10.1002/jmv.24954. [PubMed 28960353]
  5. Dawood AA, Nooh MZ, Elgamal AA. Factors associated with improved glycemic control by direct-acting antiviral agent treatment in Egyptian type 2 diabetes mellitus patients with chronic hepatitis C genotype 4. Diabetes Metab J. 2017;41(4):316-321. doi: 10.4093/dmj.2017.41.4.316. [PubMed 28868829]
  6. Dotters-Katz SK, Kuller JA, Hughes BL. Society for Maternal-Fetal Medicine consult series #56: hepatitis C in pregnancy-updated guidelines: replaces consult number 43, November 2017. Am J Obstet Gynecol. 2021;225(3):B8-B18. doi:10.1016/j.ajog.2021.06.008 [PubMed 34116035]
  7. Epclusa (sofosbuvir/velpatasvir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; June 2021.
  8. Epclusa (sofosbuvir/velpatasvir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; April 2022.
  9. Epclusa (sofosbuvir and velpatasvir) [product monograph]. Mississauga, Ontario, Canada: Gilead Sciences Canada Inc; August 2022.
  10. FDA Safety Alert. MedWatch. Direct-acting antiviral for hepatitis C: drug safety communication – risk of hepatitis B reactivating. Food and Drug Administration website. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm523690.htm. Accessed December 8, 2016.
  11. Hum J, Jou JH, Green PK, et al. Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus. Diabetes Care. 2017;40(9):1173-1180. doi:10.2337/dc17-0485 [PubMed 28659309]
  12. Smolders EJ, deKanter CT, van Hoek B, Arends JE, Drenth JP, Burger DM. Pharmacokinetics, efficacy, and safety of hepatitis C virus drugs in patients with liver and/or renal impairment. Drug Saf. 2016:39(7):589-611. [PubMed 27098247]
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