(soe FOS bue vir & vel PAT as vir)
Chronic hepatitis C: Treatment of genotype chronic hepatitis C (CHC) 1, 2, 3, 4, 5, or 6 infection in adult patients without cirrhosis or with compensated cirrhosis or in combination with ribavirin in patients with decompensated cirrhosis.
If sofosbuvir/velpatasvir is administered with ribavirin, the contraindications to ribavirin also apply. See ribavirin manufacturer " ²s labeling information.
Chronic hepatitis C (patients without cirrhosis and patients with compensated cirrhosis [Child-Pugh class A]): Oral: One tablet once daily for 12 weeks
Chronic hepatitis C (patients with decompensated cirrhosis [Child-Pugh class B and C]): Oral: One tablet once daily with concomitant ribavirin for 12 weeks
Refer to adult dosing.
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer 's labeling. However, sofosbuvir and metabolite accumulate in patients with severely impaired renal function.
End-stage renal disease (ESRD), including those requiring intermittent hemodialysis (IHD): There are no dosage adjustments provided in the manufacturers labeling However, sofosbuvir and metabolite accumulate in patients with severely impaired renal function.
Child-Pugh class A, B, or C: No dosage adjustment necessary.
Oral: Administer with or without food.
Store below 30 ‚ °C (86 ‚ °F). Dispense only in original container.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Epclusa: Sofosbuvir 400 mg and velpatasvir 100 mg
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Amiodarone: Sofosbuvir may enhance the bradycardic effect of Amiodarone. Avoid combination
Antacids: May decrease the serum concentration of Velpatasvir. Management: Separate administration of velpatasvir and antacids by at least 4 hours. Consider therapy modification
Asunaprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination
AtorvaSTATin: Velpatasvir may increase the serum concentration of AtorvaSTATin. Monitor therapy
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. 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: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification
CYP2B6 Inducers (Moderate): May decrease the serum concentration of Velpatasvir. Avoid combination
CYP2C8 Inducers (Strong): May decrease the serum concentration of Velpatasvir. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Velpatasvir. Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Velpatasvir. Avoid combination
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Digoxin: Velpatasvir may increase the serum concentration of Digoxin. Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
Grazoprevir: OATP1B1/SLCO1B1 Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination
H2-Antagonists: May decrease the serum concentration of Velpatasvir. Monitor therapy
Modafinil: May decrease the serum concentration of Sofosbuvir. Avoid combination
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Nilotinib: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
OXcarbazepine: May decrease the serum concentration of Sofosbuvir. Avoid combination
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Sofosbuvir. Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Velpatasvir. Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Proton Pump Inhibitors: May decrease the serum concentration of Velpatasvir. Avoid combination
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Rifabutin: May decrease the serum concentration of Sofosbuvir. Avoid combination
Rifapentine: May decrease the serum concentration of Sofosbuvir. Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Rosuvastatin: Velpatasvir may increase the serum concentration of Rosuvastatin. Consider therapy modification
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Tenofovir Disoproxil Fumarate: Velpatasvir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Topotecan: Velpatasvir may increase the serum concentration of Topotecan. Avoid combination
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Serum creatinine at baseline and periodically when clinically indicated; if used in patients with decompensated cirrhosis, ribavirin monitoring parameters also apply. 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.
>10%: Central nervous system: Headache (22%), fatigue (15%)
1% to 10%:
Central nervous system: Irritability ( ≥5%), insomnia (5%), depression (1%)
Dermatologic: Skin rash (2%)
Gastrointestinal: Nausea (9%), increased serum lipase (>3X ULN: 3% to 6%)
Neuromuscular & skeletal: Weakness (5%), increased creatine phosphokinase ( ≥10X ULN: 1% to 2%)
Frequency not defined: Hepatic: Increased indirect serum bilirubin (patients with HIV-1/HCV coinfection)
Sofosbuvir: Sofosbuvir AUC0-inf was 61%, 107%, and 171% higher in subjects with mild, moderate, and severe renal impairment, while the GS-331007 AUC0-inf was 55%, 88%, and 451% higher, respectively. In subjects with ESRD, relative to subjects with normal renal function, sofosbuvir and GS-331007 AUC0-inf was 28% and 1280% higher when sofosbuvir was dosed 1 hour before hemodialysis compared with 60% and 2070% higher when sofosbuvir was dosed 1 hour after hemodialysis, respectively.
Velpatasvir: No clinically relevant differences in velpatasvir pharmacokinetics were observed between healthy subjects and subjects with severe renal 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.
Velpatasvir: Velpatasvir plasma exposure (AUCinf ) was similar in subjects with moderate hepatic impairment, severe hepatic impairment, and control subjects with normal hepatic function. Population pharmacokinetics analysis in HCV-infected subjects indicated that cirrhosis (including decompensated cirrhosis) had no clinically relevant effect on the exposure of velpatasvir.
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 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.
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Adverse events were not observed in animal reproduction studies using sofosbuvir or velpatasvir. Also refer to the sofosbuvir monograph (and the ribavirin monograph if used in combination with ribavirin) for additional information.
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.
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
Velpatasvir: Urine: 94%, feces: 0.4%; Sofosbuvir: Urine: 80%; feces: 14%
Velpatasvir: 3 hours; Sofosbuvir: 0.5 to 1 hour
Velpatasvir: 15 hours; Sofosbuvir: 0.5 hours
Velpatasvir: >99.5%; Sofosbuvir: 61% to 65%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience loss of strength and energy, headache, nausea, or insomnia (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.