Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
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 (88)
- 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.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir 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 (1)
- ribociclib
ribociclib will increase the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
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
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
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.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%
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
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.
Formulary
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.
