Version May 2024
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with sofosbuvir/velpatasvir/voxilaprevir. HBV reactivation has been reported in hepatitis C virus (HCV)/HBV coinfected 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 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.
Chronic hepatitis C:
Note: Compensated cirrhosis is defined as Child-Pugh class A (AASLD/IDSA 2021).
Treatment-naive, genotype 3 with compensated cirrhosis and baseline NS5A resistance-associated substitution Y93H for velpatasvir (alternative agent): Oral: 1 tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) once daily for 12 weeks (AASLD/IDSA 2021).
Treatment-experienced patients (all genotypes) without cirrhosis or with compensated cirrhosis:
Sofosbuvir-based treatment failures: Oral: 1 tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) once daily for 12 weeks; for patients with genotype 3 and compensated cirrhosis, use in combination with weight-based ribavirin if not contraindicated (AASLD/IDSA 2021).
Elbasvir/grazoprevir-based treatment failures: Oral: 1 tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) once daily for 12 weeks (AASLD/IDSA 2021; Llaneras 2019).
Glecaprevir/pibrentasvir treatment failures: Oral: 1 tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) once daily for 12 weeks; for patients with compensated cirrhosis, use in combination with weight-based ribavirin if not contraindicated (AASLD/IDSA 2021).
Multiple direct-acting antiviral treatment failures, including sofosbuvir/velpatasvir/voxilaprevir or sofosbuvir plus glecaprevir/pibrentasvir: Oral: 1 tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) once daily in combination with weight-based ribavirin for 24 weeks (AASLD/IDSA 2021).
Chronic hepatitis C, post transplant (kidney, liver) (off-label use): Oral: 1 tablet (sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg) once daily for 12 weeks; for patients with cirrhosis and multiple negative baseline characteristics (eg, treatment experienced, genotype 3, presence of hepatocellular carcinoma), consider using in combination with ribavirin (AASLD/IDSA 2021).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild, moderate, or severe impairment: No dosage adjustment necessary.
End-stage renal disease requiring hemodialysis: No dosage adjustment necessary.
Hepatic impairment prior to treatment initiation:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate or severe impairment (Child-Pugh class B or C): Use is not recommended (due to higher voxilaprevir exposure).
Hepatotoxicity during treatment:
Asymptomatic increases in ALT <10-fold: Closely monitor with repeat testing every 2 weeks. If persistent elevation remains, consider stopping therapy (AASLD/IDSA 2021).
<10-fold increase in ALT from baseline with weakness, nausea, vomiting, jaundice, or significantly increased bilirubin, alkaline phosphatase, or INR: Discontinue direct-acting antiviral (DAA) (AASLD/IDSA 2021).
≥10-fold increase in ALT from baseline at any time during treatment: Discontinue DAA therapy, especially with signs and symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR (AASLD/IDSA 2021).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see Sofosbuvir monograph.
>10%:
Gastrointestinal: Diarrhea (13% to 14%), nausea (10% to 13%)
Hepatic: Increased serum bilirubin (4% to 13%)
Nervous system: Fatigue (17% to 19%), headache (21% to 23%)
1% to 10%:
Dermatologic: Skin rash (2%)
Gastrointestinal: Increased serum lipase (2%)
Nervous system: Asthenia (4% to 6%), depressed mood (≤1%), insomnia (3% to 6%)
<1%: Cardiovascular: Increased serum creatine kinase
Postmarketing:
Hepatic: Decompensated liver disease, hepatic failure (FDA Safety Communication 2019), severe hepatic disease (FDA Safety Communication 2019)
Infection: Reactivation of HBV
Concurrent use with rifampin.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to sofosbuvir, velpatasvir, voxilaprevir, or any component of the formulation; concurrent use with dabigatran, phenobarbital, phenytoin, rosuvastatin, or St John’s wort
Concerns related to adverse effects:
• 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 sofosbuvir/velpatasvir/voxilaprevir; 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.
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).
• Hepatic effects: Hepatic decompensation and hepatic failure (including fatal cases) have been reported; cases occurred in patients with baseline cirrhosis with and without moderate or severe liver impairment (Child-Pugh class B or C). Assess hepatic function as clinically indicated; monitor patients with compensated cirrhosis or with evidence of advanced liver disease (eg, portal hypertension) for signs/symptoms of hepatic decompensation (eg, ascites, hepatic encephalopathy, variceal hemorrhage). Discontinue treatment in patients who develop signs/symptoms of hepatic decompensation/failure.
• Hepatic impairment: Use is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B or C) or patients with history of prior hepatic decompensation.
Concurrent drug therapy issues:
• Amiodarone: Symptomatic bradycardia (some requiring pacemaker intervention) has occurred in patients receiving amiodarone and sofosbuvir in combination with daclatasvir or simeprevir. A fatal cardiac arrest was reported in a patient taking amiodarone with sofosbuvir/ledipasvir-containing regimen. 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/voxilaprevir 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 sofosbuvir/velpatasvir/voxilaprevir. Patients should seek medical attention immediately if they experience fainting or near-fainting, dizziness, light-headedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion, or memory problems.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Vosevi: Sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg
No
Tablets (Vosevi Oral)
400-100-100 mg (per each): $1,068.00
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Vosevi: Sofosbuvir 400 mg, velpatasvir 100 mg, and voxilaprevir 100 mg
Administer with food.
Hepatitis C, chronic: Treatment of adults with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh class A) who have genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor or who have genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.
Hepatitis C, chronic, post transplant (kidney, liver)
Refer to individual components.
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
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
Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: May increase the serum concentration of Voxilaprevir. 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: Voxilaprevir may increase the serum concentration of Atorvastatin. Management: Use the lowest atorvastatin dose possible if combined with voxilaprevir and monitor patients for increased statin effects/toxicities (eg, myopathy, rhabdomyolysis). Risk D: Consider therapy modification
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Voxilaprevir may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
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
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
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 (Moderate): May decrease the serum concentration of Voxilaprevir. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Velpatasvir. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Voxilaprevir. 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
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
Histamine H2 Receptor Antagonists: May decrease the serum concentration of Velpatasvir. Risk C: Monitor therapy
HMG-CoA Reductase Inhibitors (Statins): Voxilaprevir may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with voxilaprevir and monitor patients for increased statin effects/toxicities. Avoid concomitant use of voxilaprevir with rosuvastatin or pitavastatin, and limit pravastatin doses to 40 mg daily. Risk D: Consider therapy modification
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
Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Lopinavir: May increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
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
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors: May increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
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
Pitavastatin: Voxilaprevir may increase the serum concentration of Pitavastatin. 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
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
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
RifAMPin: May increase the serum concentration of Voxilaprevir. Specifically, a single dose of rifampin may increase voxilaprevir concentrations, while chronic daily use of rifampin may decrease voxilaprevir concentrations. RifAMPin may decrease the serum concentration of Voxilaprevir. 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: Voxilaprevir may increase the serum concentration of Rosuvastatin. Risk X: Avoid combination
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
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: May increase the serum concentration of Voxilaprevir. Voxilaprevir 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
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. 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
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination
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).
Adverse events were not observed in animal reproduction studies using individual components of this combination. Refer to the sofosbuvir 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]).
It is not known if sofosbuvir, velpatasvir, or voxilaprevir are present in human breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider 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]).
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 within 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.
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 2021; 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/voxilaprevir), 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).
Sofosbuvir is an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is required for viral replication and acts a s a chain terminator.
Velpatasvir is an inhibitor of the HCV NS5A protein, which is also required for viral replication.
Voxilaprevir is a noncovalent, reversible inhibitor of the NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV-encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication.
See individual agents.
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