Download Epclusa (sofosbuvir/velpatasvir)

New Drug Introduction: Epclusa®/ sofosbuvir/velpatasvir
Pharmacology
Manufacturer
Approval Date
Indications
Contraindications
Black Box Warnings
Warnings/
Precautions
Pregnancy
Lactation
Pharmacokinetics
Drug Interactions –
Object Drugs
Drug Interactions –
Precipitant drugs

Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor that
disrupts viral replication by acting as a RNA chain terminator.
 Velpatasvir prevents viral replication via inhibition of NS5A protein.
Gilead Sciences, Inc
June 28, 2016
Treatment of adult patients with chronic hepatitis C virus (HCV) genotype
1, 2, 3, 4, 5, or 6 infection
 Without cirrhosis or with compensated cirrhosis (Child-Pugh A)
 With decompensated cirrhosis (Child-Pugh B or C) in combination
with ribavirin
Same as patients for whom ribavirin is contraindicated
 Hemoglobinopathy
 Renal impairment (CrCl < 50 mL/min;
Ribasphere/Rebetol forumalation only)
 Pregnant women
 Coadministration with didanosine
Ribavirin may cause hemolytic anemia which can result in worsening
cardiac disease and lead to fatal/nonfatal myocardial infarctions. Do not
treat patients with a history of significant or unstable cardiac disease.
 Serious symptomatic bradycardia may occur in patients taking
amiodarone, especially in patients also taking beta blockers, underlying
cardiac comorbidities and/or advanced liver disease
 Coadministration of amiodarone is not recommended. If used with
amiodarone, cardiac monitoring in an inpatient setting for the first 48
hours of coadministration followed by outpatient daily heart rate
monitoring for at least the first 2 weeks of treatment
 Risk of reduced therapeutic effect due to concomitant inducers of PGP
and/or moderate to potent inducers of CYP 2B6/3A4/2C8
 Contraindicated in pregnant women and men whose female partners
are pregnant if administered with ribavirin
 No human data available to establish risk to pregnancy outcomes.
Unknown if excreted in human breast milk but was excreted in the milk of
treated rats; benefits and risks should be weighed
Sofosbuvir
Velpatasvir
A Tmax
0.5-1h
3h
Effect of high fat meal
78%
21%
(relative to fasting)
D % Bound
61-65
>99.5
Blood to plasma ratio
0.7
0.52-0.67
M Metabolism
Active Metabolite GSCYP2B6
461203; Inactive Metabolite
CYP2C8
GS-331007
CYP3A4
E % Urine
80
0.4
% Fecal
14
94
T1/2 (h)
SOF: 0.5; GS-331007: 25
15
Velpatasvir is an inhibitor of P-gp, BCRP, and OAT.
Sofosbuvir/velpatasvir may increase the concentration of topotecan,
digoxin, tenofovir, rosuvastatin, and atorvastatin
Antacids, H2RA, PPI, and efavirenz may decrease the concentration of
velpatasvir.
Carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifampin,
tipranavir/ritonavir, and St. John’s wort may decrease concentration of
sofosbuvir/velpatasvir.
Adverse Effects
Results shown for
ASTRAL-1 trial
Monitoring
Efficacy/Toxicity
Dosing –
Initial/Usual/Max
Renal Adjustment
Hepatic Adjustment
Headache (29) [28]
Fatigue (20) [20]
Nasopharyngitis (13) [10]
Nausea (12) [11]
Diarrhea (8) [7]
Asthenia (7) [8]
Determine hepatitis C genotype prior to initiation of therapy. A reduction in
HCV RNA viral load may indicate efficacy. Monitor hemoglobin (at
baseline, weeks 2 & 4, then periodically) in patients with decompensated
cirrhosis who are coadministered ribavirin.
Pts w/o cirrhosis and patients with compensated cirrhosis (Child-Pugh A)
 Sofosbuvir 400 mg / velpatasvir 100 mg once daily +/- food for 12
weeks
Patients with decompensated cirrhosis
 Sofosbuvir 400 mg / velpatasvir 100 mg once daily with or without
food + ribavirin for 12 weeks
 <75 kg: Ribavirin 1000 mg/day with food in 2 divided doses
 ≥ 75 kg: Ribavirin 1200 mg/day with food in 2 divided doses
No dose adjustment for mild or moderate renal impairment
The safety and efficacy in severe renal impairment (eGFR <30
mL/min/1.73m2) or ESRD requiring hemodialysis has not been established.
No adjustment necessary
Cost: Source: UpToDate 09/26/16
Drug Name
Zepatier (elbasvir/grazoprevir)
Harvoni (ledipasvir/sofosbuvir)
Epclusa (sofosbuvir/velpatasvir)
Dosing
$ (tablets)
elbasvir 50 mg/grazoprevir 100 mg daily
Ledispavir 90 mg/ sofosbuvir 400 mg daily
Sofosbuvir 400 mg/100 mg daily
10,920(14)
37,800 (28)
29,9904 (28)
Summary
 Epclusa is a fixed dose combination of sofosbuvir, a hepatitis C virus nucleotide
analog NS5B polymerase inhibitor and velpatasvir a HCV NS5A inhibitor indicated for
the treatment of chronic HCV genotype 1, 2, 3, 4, 5, or 6.
 Dosing is sofosbuvir 400 mg / velpatasvir 100 mg by mouth daily for 12 weeks for
patients without cirrhosis and patients with compensated cirrhosis. Ribavirin is added
for 12 weeks for patients with decompensated cirrhosis.
 Ribavirin may cause hemolytic anemia. Monitor hemoglobin (at baseline, weeks 2 & 4,
then periodically) in patients with decompensated cirrhosis coadministered ribavirin.
 Ribavirin is contraindicated in pregnancy and patients with hemoglobinopathies.
 Place in therapy: Epclusa is a first line option for HCV genotypes 1, 2, 3, 4, 5, or 6
References:
1. https://www.epclusainfo.com/
2. Epclusa (sofosbuvir and velpatasvir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; June 2016.
3. Feld, J.J, et al. Sofosbuvir and velpatasvir for hcv genotype 1, 2, 3, 4, 5, and 6 infection. N Engl J Med 2015;
373:2599-607.
4. Foster, G.R., et al. Sofosbuvir and velpatasvir for hcv genotype 2 and 3 infection. N Engl J Med 2015; 373:2608-17.
5. Curry, M.P., et al. Sofosbuvir and velpatasvir for hcv in patients with decompensated cirrhosis. N Engl J Med 2015;
373:2618-28.
Date Prepared: 09/25/2016
Editor: Peter G. Koval, Pharm.D., BCPS
Author: Kelsy Combs, Pharm.D, PGY1 Ambulatory Care Pharmacy Resident