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.
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.
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.
Children ≥3 years and Adolescents: Mild, moderate, or severe impairment: No dosage adjustment necessary.
(For additional information see "Sofosbuvir and velpatasvir: Drug information")
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 (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.
Mild, moderate, or severe impairment: No dosage adjustment necessary.
End-stage renal disease requiring hemodialysis: No dosage adjustment necessary.
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).
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)
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.
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.
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.
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
May be product dependent
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Epclusa: Sofosbuvir 400 mg and velpatasvir 100 mg
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.
Oral: Administer with or without food.
Store below 30°C (86°F). Dispense in original container.
Treatment of chronic hepatitis C virus genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (as monotherapy), or with decompensated cirrhosis in combination with ribavirin (FDA approved in ages ≥3 years and adults).
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
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
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
Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Mavorixafor. Risk C: Monitor therapy
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
Resmetirom: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Resmetirom. 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
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.
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]).
Management of hepatitis C virus (HCV) infection requires extensive monitoring; refer to current guidelines for additional guidance including response to abnormal laboratory parameters (AASLD/IDSA 2021).
Baseline:
Within 6 months prior to starting antiviral therapy: CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), SCr, calculated GFR.
Prior to starting antiviral therapy (no specific time frame): Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc); HIV testing; quantitative HCV viral load; resistance (RAS) testing (as clinically appropriate) (AASLD/IDSA 2021).
During therapy: Liver function tests (as clinically indicated); quantitative HCV viral load testing (≥12 weeks after completion of therapy) (AASLD/IDSA 2021).
In diabetes patients, monitor glucose and signs and symptoms of hypoglycemia (AASLD/IDSA 2021). 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.
If used in combination with amiodarone (or in patients who discontinued amiodarone just prior to initiating sofosbuvir), inpatient cardiac monitoring for the first 48 hours of coadministration, then daily outpatient or self-monitoring of heart rate through at least the first 2 weeks of treatment.
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.
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%
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.
Do you want to add Medilib to your home screen?