EPCLUSA (sofosbuvir 400 mg/velpatasvir 100 mg, 200 mg/50 mg tablets; 200 mg/50 mg, 150 mg/37.5 mg oral pellets) is indicated for the treatment of patients 3 years of age and older with chronic hepatitis C virus (HCV) genotype 1-6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis.
Please see below for Important Safety Information for EPCLUSA.
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.
If EPCLUSA is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.
Coadministration of amiodarone with EPCLUSA is not recommended due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir-containing regimen. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
For patients taking amiodarone who have no other alternative viable treatment options and who will be coadministered EPCLUSA:
Patients who are taking EPCLUSA who need to start amiodarone therapy due to no other alternative viable treatment options and patients discontinuing amiodarone just prior to starting EPCLUSA should undergo similar cardiac monitoring as outlined above.
Drugs that are inducers of P-gp and/or moderate to strong inducers of CYP2B6, CYP2C8, or CYP3A4 (eg, rifampin, St. John’s wort, carbamazepine) may significantly decrease plasma concentrations of sofosbuvir and/or velpatasvir, leading to potentially reduced therapeutic effect of EPCLUSA. The use of these agents with EPCLUSA is not recommended.
Adverse Reactions |
(N=624) |
---|---|
Headache | 22% |
Fatigue | 15% |
Nausea | 9% |
Asthenia | 5% |
Insomnia | 5% |
EPCLUSA (n=1/624)
vs 2%
placebo (n=2/116)
EPCLUSA (n=1/134)
vs 0%
SOF + RBV (n=0/132)
EPCLUSA (n=0/277)
vs 3%
SOF + RBV (n=9/275)
Concomitant Drug Class | Effect on Concentrationb | Clinical Effect/Recommendation |
---|---|---|
Acid-reducing agents |
Velpatasvir solubility decreases as pH increases. Drugs that increase gastric pH are expected to decrease concentration of velpatasvir. |
|
antacids (eg, aluminum and magnesium hydroxide) |
velpatasvir |
Separate antacid and EPCLUSA administration by 4 hours. |
H2-receptor antagonistsc (eg, famotidine) |
velpatasvir |
H2-receptor antagonists may be administered simultaneously with or 12 hours apart from EPCLUSA at a dose that does not exceed doses comparable to famotidine 40 mg twice daily. |
proton-pump inhibitorsc (eg, omeprazole) |
velpatasvir |
Coadministration of omeprazole or other proton-pump inhibitors is not recommended. If it is considered medically necessary to coadminister, EPCLUSA should be administered with food and taken 4 hours before omeprazole 20 mg. Use with other proton-pump inhibitors has not been studied. |
Antiarrhythmics | ||
amiodarone |
Effect on amiodarone, sofosbuvir, and velpatasvir concentrations unknown |
Coadministration of amiodarone with a sofosbuvir-containing regimen may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with EPCLUSA is not recommended; if coadministration is required, cardiac monitoring is recommended. |
digoxinc |
digoxin |
Therapeutic concentration monitoring of digoxin is recommended when coadministered with EPCLUSA. Refer to digoxin prescribing information for monitoring and dose modification recommendations for concentration increases of less than 50%. |
Anticancers | ||
topotecan |
topotecan |
Coadministration is not recommended. |
Anticonvulsants | ||
carbamazepinec, phenytoin, phenobarbital |
sofosbuvir velpatasvir |
Coadministration is not recommended. |
Antimycobacterials | ||
rifabutinc, rifampinc, rifapentine |
sofosbuvir velpatasvir |
Coadministration is not recommended. |
HIV Antiretrovirals | ||
efavirenzc |
velpatasvir |
Coadministration of EPCLUSA with efavirenz-containing regimens is not recommended. |
regimens containing tenofovir DF |
tenofovir |
Monitor for tenofovir-associated adverse reactions in patients receiving EPCLUSA concomitantly with a regimen containing tenofovir DF. Refer to the prescribing information of the tenofovir DF-containing product for recommendations on renal monitoring. |
tipranavir/ritonavir |
sofosbuvir velpatasvir |
Coadministration is not recommended. |
Herbal Supplements | ||
St. John’s wort (Hypericum perforatum) |
sofosbuvir velpatasvir |
Coadministration is not recommended. |
HMG-CoA Reductase Inhibitors | ||
rosuvastatinc |
rosuvastatin |
Coadministration of EPCLUSA with rosuvastatin may significantly increase the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis. Rosuvastatin may be administered with EPCLUSA at a dose that does not exceed 10 mg. |
atorvastatinc |
atorvastatin |
Coadministration of EPCLUSA with atorvastatin may be associated with increased risk of myopathy, including rhabdomyolysis. Monitor closely for HMG-CoA reductase inhibitor-associated adverse reactions, such as myopathy and rhabdomyolysis. |
Acid-reducing agents |
---|
Clinical Effect/Recommendation |
Velpatasvir solubility decreases as pH increases. Drugs that increase gastric pH are expected to decrease concentration of velpatasvir. |
antacids (eg, aluminum and magnesium hydroxide) |
Effect on Concentrationb |
velpatasvir |
Clinical Effect/Recommendation |
Separate antacid and EPCLUSA administration by 4 hours. |
H2-receptor antagonistsc (eg, famotidine) |
Effect on Concentrationb |
velpatasvir |
Clinical Effect/Recommendation |
H2-receptor antagonists may be administered simultaneously with or 12 hours apart from EPCLUSA at a dose that does not exceed doses comparable to famotidine 40 mg twice daily. |
proton-pump inhibitorsc (eg, omeprazole) |
Effect on Concentrationb |
velpatasvir |
Clinical Effect/Recommendation |
Coadministration of omeprazole or other proton-pump inhibitors is not recommended. If it is considered medically necessary to coadminister, EPCLUSA should be administered with food and taken 4 hours before omeprazole 20 mg. Use with other proton-pump inhibitors has not been studied. |
Antiarrhythmics |
---|
amiodarone |
Effect on Concentrationb |
Effect on amiodarone, sofosbuvir, and velpatasvir concentrations unknown |
Clinical Effect/Recommendation |
Coadministration of amiodarone with a sofosbuvir-containing regimen may result in serious symptomatic bradycardia. The mechanism of this effect is unknown. Coadministration of amiodarone with EPCLUSA is not recommended; if coadministration is required, cardiac monitoring is recommended. |
digoxinc |
Effect on Concentrationb |
digoxin |
Clinical Effect/Recommendation |
Therapeutic concentration monitoring of digoxin is recommended when coadministered with EPCLUSA. Refer to digoxin prescribing information for monitoring and dose modification recommendations for concentration increases of less than 50%. |
Anticancers |
---|
topotecan |
Effect on Concentrationb |
topotecan |
Clinical Effect/Recommendation |
Coadministration is not recommended. |
Anticonvulsants |
---|
carbamazepinec, phenytoin, phenobarbital |
Effect on Concentrationb |
sofosbuvir velpatasvir |
Clinical Effect/Recommendation |
Coadministration is not recommended. |
Antimycobacterials |
---|
rifabutinc, rifampinc, rifapentine |
Effect on Concentrationb |
sofosbuvir velpatasvir |
Clinical Effect/Recommendation |
Coadministration is not recommended. |
HIV Antiretrovirals |
---|
efavirenzc |
Effect on Concentrationb |
velpatasvir |
Clinical Effect/Recommendation |
Coadministration of EPCLUSA with efavirenz-containing regimens is not recommended. |
regimens containing tenofovir DF |
Effect on Concentrationb |
tenofovir |
Clinical Effect/Recommendation |
Monitor for tenofovir-associated adverse reactions in patients receiving EPCLUSA concomitantly with a regimen containing tenofovir DF. Refer to the prescribing information of the tenofovir DF-containing product for recommendations on renal monitoring. |
tipranavir/ritonavir |
Effect on Concentrationb |
sofosbuvir velpatasvir |
Clinical Effect/Recommendation |
Coadministration is not recommended. |
Herbal Supplements |
---|
St. John’s wort (Hypericum perforatum) |
Effect on Concentrationb |
sofosbuvir velpatasvir |
Clinical Effect/Recommendation |
Coadministration is not recommended. |
HMG-CoA Reductase Inhibitors |
---|
rosuvastatinc |
Effect on Concentrationb |
rosuvastatin |
Clinical Effect/Recommendation |
Coadministration of EPCLUSA with rosuvastatin may significantly increase the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis. Rosuvastatin may be administered with EPCLUSA at a dose that does not exceed 10 mg. |
atorvastatinc |
Effect on Concentrationb |
atorvastatin |
Clinical Effect/Recommendation |
Coadministration of EPCLUSA with atorvastatin may be associated with increased risk of myopathy, including rhabdomyolysis. Monitor closely for HMG-CoA reductase inhibitor-associated adverse reactions, such as myopathy and rhabdomyolysis. |
aThis table is not all inclusive
b = decrease, = increase
cThese interactions have been studied in healthy adults.
Consult the full Prescribing Information for EPCLUSA (sofosbuvir/velpatasvir) for more information on potentially significant drug interactions, including clinical comments.
Click here to download the full Prescribing Information (PI) or Package Insert for EPCLUSA.
Adverse Events (All Grades) Reported in ≥5% of Subjects in POLARIS-2 and -3
Adverse Events |
POLARIS-2
(N=440) |
POLARIS-3
(N=109) |
---|---|---|
Headache | 23% | 29% |
Fatigue | 20% | 28% |
Nausea | 9% | 9% |
Diarrhea | 7% | 5% |
Asthenia | 6% | 5% |
Insomnia | 5% | 5% |
Arthralgia | 5% | <5% |
Myalgia | <5% | 6% |
Upper abdominal pain | <5% | 6% |
Back pain | <5% | 6% |
Abdominal pain | <5% | 5% |
Discontinuations due to AEs in POLARIS-2: <1% (n=2/440).5
Discontinuations due to AEs in POLARIS-3: 1% (n=1/109).5
aDerived from the HCV-TARGET, HepaC, HELIOS, and Mangia cohorts. Adverse reaction data were not reported in the other cohorts.
Most Common Adverse Reactions
Adverse Events |
(n=103) |
---|---|
Fatigue | 18% |
Headache | 11% |
Nausea | 13% |
Single-arm trial of TN and TE adults
with
ESRD without cirrhosis
or with compensated cirrhosis
Low rates of AEs leading to EPCLUSA discontinuation and low rates of treatment-related Grade 3 or 4 or serious AEs were similarly observed among patients taking EPCLUSA with or without concomitant PPI use
AEs |
EPCLUSA With PPI Use (n=87) n (%) |
EPCLUSA Without PPI Use (n=2517) n (%) |
---|---|---|
Treatment-emergent |
68 (78) |
1662 (66) |
Grade 3 or 4 |
7 (8) |
58 (2) |
Treatment-related Grade 3 or 4 |
1 (1) |
11 (<1) |
Serious |
10 (11) |
45 (2) |
Treatment-related Serious |
0 (0) |
0 (0) |
Discontinuations due to AEs |
1 (1) |
9 (<1) |
Deaths |
0 (0) |
5 (<1) |
BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. 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.
EPCLUSA (sofosbuvir 400 mg/velpatasvir 100 mg, 200 mg/50 mg tablets; 200 mg/50 mg, 150 mg/37.5 mg oral pellets) is indicated for the treatment of patients 3 years of age and older with chronic hepatitis C virus (HCV) genotype 1-6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis.
Consult the full Prescribing Information for EPCLUSA for more information on potentially significant drug interactions, including clinical comments.
Please see full Prescribing Information for EPCLUSA, including BOXED WARNING.
BOXED WARNING: RISK OF HEPATITIS B : REACTIVATIONTest all patients for evidence of current or prior hepatitis B virus (HBV)...
EPCLUSA (sofosbuvir 400 mg/velpatasvir 100 mg, 200 mg/50 mg tablets; 200 mg/50 mg, 150 mg/37.5 mg oral pellets) is indicated for the treatment of patients 3 years of age and older with chronic hepatitis C virus (HCV) genotype 1-6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis.
AE = adverse event; DF = disoproxil fumarate; ESRD = end-stage renal disease; GT = genotype; HIV = human immunodeficiency virus; INR = international normalized ratio; PPI = proton-pump inhibitor; RBV = ribavirin; SOF = sofosbuvir, TE = treatment-experienced; TN = treatment-naïve.
References: