sofosbuvir/velpatasvir (Rx)

Brand and Other Names:Epclusa
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

sofosbuvir/velpatasvir

tablet

  • 400mg/100mg

Chronic Hepatitis C

Indicated for chronic hepatitis C virus (HCV) infection in adults with HCV genotypes 1, 2, 3, 4, 5, and 6 without cirrhosis or with compensated cirrhosis; or with decompensated cirrhosis for use in combination with ribavirin

1 tablet (400 mg sofosbuvir/100 mg velpatasvir) PO qDay

Treatment duration for treatment-naïve and treatment-experienced liver transplant recipients

  • Without cirrhosis or with compensated cirrhosis (Child-Pugh A): Sofosbuvir/velpatasvir for 12 weeks
  • With decompensated cirrhosis (Child-Pugh B or C): Sofosbuvir/velpatasvir plus ribavirin for 12 weeks
  • Weight-based ribavirin dose
    • <75 kg: 1000 mg/day PO divided BID
    • ≥75 kg: 1200 mg/day PO divided BID
    • Modify ribavirin starting dose and on-treatment dosage based on hemoglobin and creatinine clearance

Dosage Modifications

Refer to ribavirin prescribing information for dosage modifications

Renal impairment

  • Any degree of renal impairment, including patients requiring dialysis: No dosage adjustment required

Hepatic impairment

  • Mild, moderate, or severe (Child-Pugh A, B, or C): No dosage adjustment required

Dosing Considerations

  • Test for evidence of current or prior hepatitis B virus (HBV) infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment
  • The safety and effectiveness of therapy in subjects who self-reported injection drug use, including in those on concomitant medication-assisted treatment (MAT), were similar to the known safety and effectiveness profile of the drug combination; no dosage adjustment recommended for people who inject drug (PWID), including those on MAT for opioid use disorder

Dosage Forms & Strengths

sofosbuvir/velpatasvir

tablet

  • 200mg/50mg
  • 400mg/100mg

oral pellets

  • 150mg/37.5mg
  • 200mg/50mg

Chronic Hepatitis C

Indicated for chronic hepatitis C virus (HCV) infection in adults and children aged ≥3 years with HCV genotypes 1, 2, 3, 4, 5, and 6 without cirrhosis or with compensated cirrhosis; or with decompensated cirrhosis for use in combination with ribavirin

<3 years: Safety and efficacy not established

≥3 years

  • Oral pellets
    • <17 kg: 150 mg sofosbuvir/37.5 mg velpatasvir PO qDay
  • Oral tablet(s) or pellets
    • 17 to <30 kg: 200 mg sofosbuvir/50 mg velpatasvir PO qDay
    • ≥30 kg: 400 mg sofosbuvir/100 mg velpatasvir PO qDay
  • Treatment duration for treatment-naïve and treatment-experienced liver transplant recipients
    • Without cirrhosis or with compensated cirrhosis (Child-Pugh A): Sofosbuvir/velpatasvir for 12 weeks
    • With decompensated cirrhosis (Child-Pugh B or C): Sofosbuvir/velpatasvir plus ribavirin for 12 weeks
  • Weight-based ribavirin dose
    • <47 kg: 15 mg/kg/day PO (divided dose AM and PM)
    • 47-49 kg: 600 mg/day PO (1 x 200 mg AM, 2 x 200 mg PM)
    • 50-65 kg: 800 mg/day PO (2 x 200 mg AM, 2 x 200 mg PM)
    • 66-80 kg: 1000 mg/day PO (2 x 200 mg AM, 3 x 200 mg PM)
    • >80 kg: 1200 mg/day PO (3 x 200 mg AM, 3 x 200 mg PM)
    • Modify ribavirin starting dose and on-treatment dosage based on hemoglobin and creatinine clearance

Dosage Modifications

Refer to ribavirin prescribing information for dosage modifications

Renal impairment

  • Any degree of renal impairment, including patients requiring dialysis: No dosage adjustment required

Hepatic impairment

  • Mild, moderate, or severe (Child-Pugh A, B, or C): No dosage adjustment required
  • Monitor liver function (including direct bilirubin), as clinically indicated for patients with decompensated cirrhosis receiving treatment with ribavirin

Dosing Considerations

Test for evidence of current or prior hepatitis B virus (HBV) infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment

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Interactions

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              Serious - Use Alternative (44)

              • amiodarone

                sofosbuvir/velpatasvir increases toxicity of amiodarone by unknown mechanism. Avoid or Use Alternate Drug. Postmarketing reports describe bradycardia resulting in death or pacemaker insertion when amiodarone was coadministered with sofosbuvir in combination with another direct acting antiviral. Patients also taking beta blockers (7 of 9 of the postmarketing reports), or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. If coadministration is required, cardiac monitoring in an inpatient setting for the first 48 hr of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

              • apalutamide

                apalutamide will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

              • armodafinil

                armodafinil will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • bosentan

                bosentan will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • carbamazepine

                carbamazepine will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                carbamazepine will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                carbamazepine will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • clobazam

                clobazam will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • colchicine

                sofosbuvir/velpatasvir will increase the level or effect of colchicine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid use of colchicine with P-gp inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with P-gp inhibitors is contraindicated in patients with renal or hepatic impairment.

              • dabrafenib

                dabrafenib will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • dexamethasone

                dexamethasone will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • dexlansoprazole

                dexlansoprazole will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Coadministration of sofosbuvir/velpatasvir with omeprazole or other PPIs is not recommended. If considered medically necessary, give sofosbuvir/velpatasvir with food 4 hr before omeprazole 20 mg. Use with other PPIs has not been studied.

              • efavirenz

                efavirenz will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • enzalutamide

                enzalutamide will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • eslicarbazepine acetate

                eslicarbazepine acetate will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • esomeprazole

                esomeprazole will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Coadministration of sofosbuvir/velpatasvir with omeprazole or other PPIs is not recommended. If considered medically necessary, give sofosbuvir/velpatasvir with food 4 hr before omeprazole 20 mg. Use with other PPIs has not been studied.

              • etravirine

                etravirine will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                fosphenytoin will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                fosphenytoin will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • lansoprazole

                lansoprazole will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Coadministration of sofosbuvir/velpatasvir with omeprazole or other PPIs is not recommended. If considered medically necessary, give sofosbuvir/velpatasvir with food 4 hr before omeprazole 20 mg. Use with other PPIs has not been studied.

              • lonafarnib

                lonafarnib will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

              • lorlatinib

                lorlatinib will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • mitotane

                mitotane will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • nafcillin

                nafcillin will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • nefazodone

                nefazodone will increase the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              • neratinib

                sofosbuvir/velpatasvir will increase the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inhibitors.

              • nevirapine

                nevirapine will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                nevirapine will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • omeprazole

                omeprazole will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Coadministration of sofosbuvir/velpatasvir with omeprazole or other PPIs is not recommended. If considered medically necessary, give sofosbuvir/velpatasvir with food 4 hr before omeprazole 20 mg. Use with other PPIs has not been studied.

              • oxcarbazepine

                oxcarbazepine will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • pantoprazole

                pantoprazole will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Coadministration of sofosbuvir/velpatasvir with omeprazole or other PPIs is not recommended. If considered medically necessary, give sofosbuvir/velpatasvir with food 4 hr before omeprazole 20 mg. Use with other PPIs has not been studied.

              • pentobarbital

                pentobarbital will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • phenobarbital

                phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • phenytoin

                phenytoin will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                phenytoin will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                phenytoin will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • primidone

                primidone will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                primidone will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                primidone will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • rabeprazole

                rabeprazole will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Coadministration of sofosbuvir/velpatasvir with omeprazole or other PPIs is not recommended. If considered medically necessary, give sofosbuvir/velpatasvir with food 4 hr before omeprazole 20 mg. Use with other PPIs has not been studied.

              • rifabutin

                rifabutin will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • rifampin

                rifampin will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                rifampin will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                rifampin will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • rifapentine

                rifapentine will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • rimegepant

                sofosbuvir/velpatasvir will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              • sotorasib

                sotorasib will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

              • St John's Wort

                St John's Wort will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                St John's Wort will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • tepotinib

                tepotinib will increase the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

              • tipranavir

                tipranavir will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

                tipranavir will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • topotecan

                sofosbuvir/velpatasvir will increase the level or effect of topotecan by Other (see comment). Avoid or Use Alternate Drug. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • vinblastine

                vinblastine will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

              • voxelotor

                voxelotor will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

              Monitor Closely (87)

              • acalabrutinib

                sofosbuvir/velpatasvir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.

              • alfentanil

                sofosbuvir/velpatasvir increases levels of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • alprazolam

                sofosbuvir/velpatasvir increases levels of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • aluminum hydroxide

                aluminum hydroxide will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Separate administration of sofosbuvir/velpatasvir from antacids by at least 4 hr.

              • aluminum hydroxide/magnesium carbonate

                aluminum hydroxide/magnesium carbonate will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Separate administration of sofosbuvir/velpatasvir from antacids by at least 4 hr.

              • aluminum hydroxide/magnesium trisilicate

                aluminum hydroxide/magnesium trisilicate will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Separate administration of sofosbuvir/velpatasvir from antacids by at least 4 hr.

              • ambrisentan

                sofosbuvir/velpatasvir increases levels of ambrisentan by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • armodafinil

                sofosbuvir/velpatasvir increases levels of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • aspirin/citric acid/sodium bicarbonate

                aspirin/citric acid/sodium bicarbonate will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Separate administration of sofosbuvir/velpatasvir from antacids by at least 4 hr.

              • atazanavir

                atazanavir will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • atorvastatin

                sofosbuvir/velpatasvir increases levels of atorvastatin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Velpatasvir is an inhibitor of OATP1B1, OATP1B3, and OATP2B1 transporters. Coadministration may increase systemic exposure of drugs that are substrates of these transporters. Coadministration may significantly increase atorvastatin serum concentration, which is associated with increased risk of myopathy, including rhabdomyolysis.

                sofosbuvir/velpatasvir will increase the level or effect of atorvastatin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of sofosbuvir/velpatasvir with atorvastatin may be associated withincreased risk of myopathy,including rhabdomyolysis. Monitor closely.

              • betrixaban

                sofosbuvir/velpatasvir increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.

              • calcium carbonate

                calcium carbonate will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Separate administration of sofosbuvir/velpatasvir from antacids by at least 4 hr.

              • caspofungin

                sofosbuvir/velpatasvir increases levels of caspofungin by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • chloramphenicol

                chloramphenicol will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • chlorothiazide

                sofosbuvir/velpatasvir will increase the level or effect of chlorothiazide by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • cimetidine

                cimetidine will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). H2 receptor antagonists may be administered simultaneously with or 12 hr apart from sofosbuvir/velpatasvir at a dose that does not exceed doses comparable to famotidine 40 mg BID.

                sofosbuvir/velpatasvir will increase the level or effect of cimetidine by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • citric acid/sodium bicarbonate

                citric acid/sodium bicarbonate will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Separate administration of sofosbuvir/velpatasvir from antacids by at least 4 hr.

              • clarithromycin

                clarithromycin will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • clonidine

                sofosbuvir/velpatasvir increases levels of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • colchicine

                sofosbuvir/velpatasvir increases levels of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • conivaptan

                conivaptan will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • daunorubicin

                sofosbuvir/velpatasvir will increase the level or effect of daunorubicin by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • deflazacort

                sofosbuvir/velpatasvir will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

              • diazepam

                sofosbuvir/velpatasvir increases levels of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • digoxin

                sofosbuvir/velpatasvir will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Velpatasvir inhibits P-gp. Monitor digoxin levels if coadministered. Refer to digoxin prescribing information for monitoring and dose modification recommendations for digoxin concentration increases of <50%.

              • dihydroergotamine

                sofosbuvir/velpatasvir increases levels of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • dipyridamole

                sofosbuvir/velpatasvir will increase the level or effect of dipyridamole by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • disopyramide

                sofosbuvir/velpatasvir increases levels of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • doxorubicin

                sofosbuvir/velpatasvir will increase the level or effect of doxorubicin by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • elagolix

                elagolix decreases levels of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

              • elbasvir/grazoprevir

                sofosbuvir/velpatasvir increases levels of elbasvir/grazoprevir by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • eluxadoline

                sofosbuvir/velpatasvir increases levels of eluxadoline by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • enalapril

                sofosbuvir/velpatasvir increases levels of enalapril by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • ergotamine

                sofosbuvir/velpatasvir increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • everolimus

                sofosbuvir/velpatasvir will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Velpatasvir inhibits P-gp. Closely monitor P-gp substrates, particularly those with a narrow therapeutic index. Modify dose if needed.

                sofosbuvir/velpatasvir increases levels of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • ezetimibe

                sofosbuvir/velpatasvir increases levels of ezetimibe by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • famotidine

                famotidine will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). H2 receptor antagonists may be administered simultaneously with or 12 hr apart from sofosbuvir/velpatasvir at a dose that does not exceed doses comparable to famotidine 40 mg BID.

              • fexofenadine

                sofosbuvir/velpatasvir increases levels of fexofenadine by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • fluvastatin

                sofosbuvir/velpatasvir increases levels of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • fluvoxamine

                fluvoxamine will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

              • glyburide

                sofosbuvir/velpatasvir will increase the level or effect of glyburide by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • guanfacine

                sofosbuvir/velpatasvir will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.

              • ibuprofen/famotidine

                ibuprofen/famotidine will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). H2 receptor antagonists may be administered simultaneously with or 12 hr apart from sofosbuvir/velpatasvir at a dose that does not exceed doses comparable to famotidine 40 mg BID.

              • imatinib

                sofosbuvir/velpatasvir will increase the level or effect of imatinib by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • indinavir

                indinavir will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • irinotecan

                sofosbuvir/velpatasvir will increase the level or effect of irinotecan by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • istradefylline

                istradefylline will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              • itraconazole

                itraconazole will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ivosidenib

                ivosidenib will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lapatinib

                sofosbuvir/velpatasvir will increase the level or effect of lapatinib by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • leflunomide

                sofosbuvir/velpatasvir will increase the level or effect of leflunomide by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • lemborexant

                lemborexant will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Monitor CYP2B6 substrate for adequate clinical response. Consider increasing the CYP2B6 substrate dose according to specific prescribing recommendations.

              • lenvatinib

                sofosbuvir/velpatasvir will increase the level or effect of lenvatinib by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • levoketoconazole

                levoketoconazole will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lonafarnib

                lonafarnib will increase the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

              • magnesium oxide

                magnesium oxide will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Separate administration of sofosbuvir/velpatasvir from antacids by at least 4 hr.

              • methotrexate

                sofosbuvir/velpatasvir will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • midazolam

                sofosbuvir/velpatasvir increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • mifepristone

                mifepristone will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • mitoxantrone

                sofosbuvir/velpatasvir will increase the level or effect of mitoxantrone by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • modafinil

                sofosbuvir/velpatasvir increases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • naldemedine

                sofosbuvir/velpatasvir increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.

                sofosbuvir/velpatasvir increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.

              • nefazodone

                nefazodone will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nelfinavir

                nelfinavir will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nirmatrelvir

                nirmatrelvir will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nitrofurantoin

                sofosbuvir/velpatasvir will increase the level or effect of nitrofurantoin by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • nizatidine

                nizatidine will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). H2 receptor antagonists may be administered simultaneously with or 12 hr apart from sofosbuvir/velpatasvir at a dose that does not exceed doses comparable to famotidine 40 mg BID.

              • olmesartan

                sofosbuvir/velpatasvir increases levels of olmesartan by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • pitavastatin

                sofosbuvir/velpatasvir increases levels of pitavastatin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Velpatasvir is an inhibitor of OATP1B1, OATP1B3, and OATP2B1 transporters. Coadministration may increase systemic exposure of drugs that are substrates of these transporters. Coadministration may significantly increase pitavastatin serum concentration, which is associated with increased risk of myopathy, including rhabdomyolysis.

              • posaconazole

                posaconazole will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • quinidine

                sofosbuvir/velpatasvir increases levels of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • regorafenib

                regorafenib will increase the level or effect of sofosbuvir/velpatasvir by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.

              • repaglinide

                sofosbuvir/velpatasvir increases levels of repaglinide by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • riociguat

                sofosbuvir/velpatasvir will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • rosuvastatin

                sofosbuvir/velpatasvir will increase the level or effect of rosuvastatin by Other (see comment). Modify Therapy/Monitor Closely. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates. Coadministration may significantly increase rosuvastatin serum concentration, which is associated with increased risk of myopathy, including rhabdomyolysis. If coadministered, do not exceed rosuvastatin dose of 10 mg/day.

                sofosbuvir/velpatasvir will increase the level or effect of rosuvastatin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of sofosbuvir/velpatasvir with rosuvastatin may significantly increase the concentration of rosuvastatin, which may increase risk of myopathy,including rhabdomyolysis. Rosuvastatin may beadministered with sofosbuvir/velpatasvir at a dose that does not exceed 10 mg.

              • safinamide

                safinamide will increase the level or effect of sofosbuvir/velpatasvir by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

              • saquinavir

                saquinavir will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • selexipag

                sofosbuvir/velpatasvir will increase the level or effect of selexipag by Other (see comment). Use Caution/Monitor. Selexipag is a ABCG2 (BCRP) substrate. Monitor selexipag for increased pharmacologic or adverse effects when coadministered with ABCG2 (BCRP) inhibitors.

              • simvastatin

                sofosbuvir/velpatasvir will increase the level or effect of simvastatin by Other (see comment). Modify Therapy/Monitor Closely. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates. Coadministration may significantly increase simvastatin serum concentration, which is associated with increased risk of myopathy, including rhabdomyolysis.

              • sirolimus

                sofosbuvir/velpatasvir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Velpatasvir inhibits P-gp. Closely monitor P-gp substrates, particularly those with a narrow therapeutic index. Modify dose if needed.

                sofosbuvir/velpatasvir increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • sulfasalazine

                sofosbuvir/velpatasvir will increase the level or effect of sulfasalazine by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.

              • temsirolimus

                sofosbuvir/velpatasvir will increase the level or effect of temsirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Velpatasvir inhibits P-gp. Closely monitor P-gp substrates, particularly those with a narrow therapeutic index. Modify dose if needed.

              • tenofovir DF

                sofosbuvir/velpatasvir will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for tenofovir-associated adverse reactions in patients receiving EPCLUSA concomitantly with a regimen containing tenofovir DF

              • triazolam

                sofosbuvir/velpatasvir increases levels of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • valsartan

                sofosbuvir/velpatasvir increases levels of valsartan by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

              • voriconazole

                voriconazole will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              Minor (2)

              • nirmatrelvir/ritonavir

                nirmatrelvir/ritonavir will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

              • ribociclib

                ribociclib will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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              Adverse Effects

              >10%

              Without cirrhosis or with compensated cirrhosis

              • Headache (22%)
              • Fatigue (15%)

              With decompensated cirrhosis

              • Fatigue (32%)
              • Anemia (26%)
              • Hemoglobin <10 g/dL (23%)
              • Nausea (15%)
              • Headache 11%)
              • Insomnia (11%)

              1-10%

              Without cirrhosis or with compensated cirrhosis

              • Nausea (9%)
              • Asthenia (5%)
              • Insomnia (5%)
              • Lipase increase >3 x ULN (3%)
              • Rash (2%)
              • Depression (1%)
              • Increased creatinine kinase ≥10 x ULN (1%)

              With decompensated cirrhosis

              • Diarrhea (10%)
              • Hemoglobin <3.5 g/dL (7%)
              • Rash (5%)
              • Increased creatinine kinase ≥10 x ULN (2%)

              Postmarketing Reports

              Cardiac disorders: Serious symptomatic bradycardia has been reported in patients taking amiodarone who initiated treatment with sofosbuvir in combination with another HCV direct-acting antiviral

              Skin and subcutaneous tissue disorders: Angioedema

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              Warnings

              Black Box Warnings

              Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct acting antivirals (DDAs)

              HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with DDAs 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

              Contraindications

              Sofosbuvir/velpatasvir plus ribavirin combination regimen is contraindicated in patients for whom ribavirin is contraindicated

              Cautions

              Hepatitis B virus reactivation

              • Hepatitis B virus (HBV) reactivation reported in HCV/HBV coinfected patients undergoing or who completed treatment with HCV DDAs, and were not receiving HBV antiviral therapy
              • HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level (see Black Box Warnings and Dosing Considerations)
              • HBV reactivation also reported in patients receiving certain immunosuppressants or chemotherapeutic agents
              • Risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may increase in these patients
              • Reactivation of HBV replication may be accompanied by hepatitis, eg, increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death may occur
              • In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment and during post-treatment follow-up; initiate appropriate patient management for HBV infection as clinically indicated
              • If administered with ribavirin, warnings and precautions for ribavirin apply to this combination; see ribavirin prescribing information

              Bradycardia

              • Coadministration with amiodarone is not recommended
              • Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention reported when amiodarone coadministered with regimen
              • Serious symptomatic bradycardia may occur if sofosbuvir is coadministered with amiodarone in combination with another direct-acting antiviral (eg, daclatasvir, simeprevir)
              • Bradycardia has generally occurred within hours to days, but reports have been observed up to 2 weeks after initiating HCV treatment
              • Patients also taking beta-blockers, or those with underlying cardiac comorbidities, and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone
              • For patients taking amiodarone who have no other alternative viable treatment options and who will require coadministration, counsel patients about risk of symptomatic bradycardia and monitor cardiac activity in an in-patient setting for first 48 hours of coadministration, after which outpatient or self-monitoring of heart rate should occur on a daily basis through at least first 2 weeks of treatment
              • Patients receiving therapy who need to start amiodarone therapy due to no other alternative viable treatment options should undergo similar cardiac monitoring as outlined above
              • Because of amiodarone’s long half-life, patients discontinuing amiodarone just prior to starting therapy should also undergo similar cardiac monitoring

              Drug interaction overview

              • Drugs affecting sofosbuvir/velpatasvir
                • Sofosbuvir and velpatasvir are substrates of drug transporters P-gp and BCRP while GS-331007 (the predominant circulating metabolite of sofosbuvir) is not
                • In vitro, slow metabolic turnover of velpatasvir by CYP2B6, CYP2C8, and CYP3A4 was observed
                • Drugs that are potent P-gp inducers and/or moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 (eg, rifampin, carbamazepine, St. John’s wort) may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect; avoid coadministration
              • Drugs that increase gastric pH
                • Coadministration with drugs that increase gastric pH are expected to decrease velpatasvir serum concentration
                • See the Administration section for how long is needed between sofosbuvir/velpatasvir doses and drugs that increase gastric pH
              • Sofosbuvir/velpatasvir effect on other drugs
                • Velpatasvir inhibits drug transporters P-gp, BCRP, OATP1B1, OATP1B3, and OATP2B1
                • Coadministration with drugs that are substrates of these transporters may increase the exposure of such drugs
                • Frequent monitoring of relevant laboratory parameters (eg, International Normalized Ratio [INR] in patients taking warfarin, blood glucose levels in diabetic patients) or drug concentrations of concomitant medications such as cytochrome P450 substrates with a narrow therapeutic index (eg, certain immunosuppressants) recommended to ensure safe and effective use; dose adjustments of concomitant medications may be necessary
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              Pregnancy

              Pregnancy

              Contraindicated if administered with ribavirin in pregnant women and in men whose female partners are pregnant

              There are no adequate data available to establish pregnancy risk for sofosbuvir or velpatasvir

              Lactation

              Unknown if sofosbuvir, velpatasvir, or their metabolites are distributed in human breast milk

              Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

              If regimen includes ribavirin, refer to ribavirin prescribing information

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Sofosbuvir: Inhibitor of HCV NS5B RNA-dependent polymerase; its inhibition, in turn, suppresses viral replication

              Velpatasvir: Pangenotypic HCV NS5A inhibitor; the NS5A protein is required for viral replication

              Absorption

              Velpatasvir solubility decreases as gastric pH increases; practically insoluble (<0.1 mg/mL) at pH >5

              Peak concentration time

              • Sofosbuvir: 0.5-1 hr
              • Velpatasvir: 3 hr

              Peak plasma concentration

              • Sofosbuvir: 567 ng/mL
              • Velpatasvir: 259 ng/mL

              AUC

              • Sofosbuvir: 1268 ng·hr/mL
              • Velpatasvir: 2980 ng·hr/mL

              Distribution

              Protein bound

              • Sofosbuvir: 61-65%
              • Velpatasvir: >99.5%

              Metabolism

              Sofosbuvir

              • Liver metabolism by cathepsin A, CES1, and HINT1
              • Substrate of P-gp transporter and breast cancer resistance protein (substrate for sofosbuvir but not metabolite GS-331007)

              Velpatasvir

              • Substrate of P-gp transporter, CYP2B6, 2C8, and 3A4

              Elimination

              Half-life

              • Sofosbuvir: 0.5 hr; GS-33107 25 hr (active metabolite)
              • Velpatasvir: 15 hr

              Excretion

              • Major route of elimination
                • Sofosbuvir: Metabolism
                • GS-33107: Glomerular filtration and active tubular secretion
                • Velpatasvir: Biliary excretion as parent compound (77%)
              • Urine
                • Sofosbuvir: 80%
                • Velpatasvir: 14%
              • Feces
                • Sofosbuvir: 0.4%
                • Velpatasvir: 94%
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              Administration

              See oral pellets full instructions for use

              Oral Pellet Preparation

              Do not chew oral pellets to avoid a bitter aftertaste

              Oral pellets can be taken directly in the mouth or mixed with food

              Administer with food to increase tolerability/palatability in children aged <6 years of age

              Sprinkle oral pellets on ≥1 spoonfuls of nonacidic soft food (eg, pudding, chocolate syrup, ice cream) at or below room temperature

              Take oral pellets within 15 minutes of gently mixing with food and swallow the entire contents without chewing

              Do not store and reuse any leftover oral pellets or mixture

              Oral Administration

              Take regularly at about the same time each day

              May take with or without food

              Oral pellets: Do not chew

              If coadministered with ribavirin, take with food

              Use with drugs that increase gastric pH

              • Coadministration with drugs that increase gastric pH are expected to decrease velpatasvir serum concentration
              • Antacids: Separate administration of sofosbuvir/velpatasvir by at least 4 hr
              • H2-antagonists: May be administered simultaneously with or 12 hr apart from sofosbuvir/velpatasvir at a dose that does not exceed doses comparable to famotidine 40 mg BID
              • PPIs: Coadministration with omeprazole or other PPIs is not recommended; if considered medically necessary, give sofosbuvir/velpatasvir with food 4 hr before omeprazole 20 mg; use with other PPIs has not been studied

              Storage

              Tablets or pellets: Store below 30°C (86 ºF)

              Dispense only in original container

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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              sofosbuvir-velpatasvir oral
              -
              400-100 mg tablet
              Epclusa oral
              -
              400-100 mg tablet

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.