Sofosbuvir and Velpatasvir- Epclusa-@-(June 2016) - Anti-Viral
Drug Name:Sofosbuvir and Velpatasvir- Epclusa-@-(June 2016) - Anti-Viral
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Other Information
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS
P-gp inducers and/or moderate to potent CYP inducers (e.g.,rifampin,
St. John’s wort, carbamazepine):
May decrease concentrations of sofosbuvir and/or velpatasvir.
Use of EPCLUSA with P-gp inducers and/or moderate to potent CYP
inducers is not recommended.
Indication:
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use
on Approval date
14. Epclusa Sofosbuvir and 6/28/2016
Velpatasvir
Approved by FDA on 6/28/2016 (Ref- FDA approved List- 2016)
To treat all six major forms of hepatitis C Virus
Press Release
Drug trials snapshot
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
EPCLUSA safely and effectively. See full prescribing information
for EPCLUSA.
EPCLUSA® (sofosbuvir and velpatasvir) tablets, for oral use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
EPCLUSA is a fixed-dose combination of sofosbuvir, a hepatitis C virus (HCV)
nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an HCV NS5A
inhibitor, and is indicated for the treatment of adult patients with chronic HCV
genotype 1, 2, 3, 4, 5 or 6 infection:
without cirrhosis or with compensated cirrhosis
with decompensated cirrhosis for use in combination with ribavirin
Adverse Reaction:
ADVERSE REACTIONS
The most common adverse reactions (incidence greater than or equal to 10%,
all grades) observed with treatment with EPCLUSA for 12 weeks are headache
and fatigue.
The most common adverse reactions (incidence greater than or equal to 10%,
all grades) observed with treatment with EPCLUSA and ribavirin for 12 weeks
in patients with decompensated cirrhosis are fatigue, anemia, nausea, headache,
insomnia and diarrhea.
Contra-Indications:
CONTRAINDICATIONS
EPCLUSA and ribavirin combination regimen is contraindicated in patients
for whom ribavirin is contraindicated
WARNINGS AND PRECAUTIONS
Bradycardia with amiodarone coadministration: Serious symptomatic
bradycardia may occur in patients taking amiodarone, particularly in patients
also receiving beta blockers, or those with underlying cardiac comorbidities
and/or advanced liver disease.
Coadministration of amiodarone with EPCLUSA is not recommended.
In patients without alternative viable treatment options, cardiac monitoring
is recommended.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
EPCLUSA is a fixed-dose combination of sofosbuvir, a hepatitis C virus (HCV)
nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an HCV NS5A
inhibitor, and is indicated for the treatment of adult patients with chronic HCV
genotype 1, 2, 3, 4, 5 or 6 infection:
without cirrhosis or with compensated cirrhosis
with decompensated cirrhosis for use in combination with ribavirin
DOSAGE AND ADMINISTRATION
Recommended dosage: One tablet (400 mg of sofosbuvir and
100 mg of velpatasvir) taken orally once daily with or without food
DOSAGE FORMS AND STRENGTHS
Tablets: 400 mg sofosbuvir and 100 mg velpatasvir
Other Information:
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to useEPCLUSA safely and effectively. See full prescribing information for EPCLUSA.
EPCLUSA® (sofosbuvir and velpatasvir) tablets, for oral use Initial U.S. Approval: 2016
-------------------------------INDICATIONS AND USAGE------------------------EPCLUSA
is a fixed-dose combination of sofosbuvir, a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor, and velpatasvir, an HCV NS5A inhibitor, and is indicated for the treatment of adult patients with chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection (1):
•
without cirrhosis or with compensated cirrhosis
•
with decompensated cirrhosis for use in combination with ribavirin
------------------------DOSAGE AND ADMINISTRATION----------------------•
Recommended dosage: One tablet (400 mg of sofosbuvir and 100 mg of velpatasvir) taken orally once daily with or without food
(2.1)
•
See recommended treatment regimen and duration i
--------------------------------CONTRAINDICATIONS-----------------------------EPCLUSA
and ribavirin combination regimen is contraindicated in patients for whom ribavirin is contraindicated (4)
-------------------------WARNINGS AND PRECAUTIONS---------------------Bradycardia
with amiodarone coadministration: Serious symptomatic bradycardia may occur in patients taking amiodarone, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with EPCLUSA is not recommended. In patients without alternative viable treatment options, cardiac monitoring is recommended. (5.1, 7.3)
-------------------------------ADVERSE REACTIONS----------------------------•
The most common adverse reactions (incidence greater than or equal to 10%, all grades) observed with treatment with EPCLUSA for 12 weeks are headache and fatigue. (6.1)
•
The most common adverse reactions (incidence greater than or equal to 10%, all grades) observed with treatment with EPCLUSA and ribavirin for 12 weeks in patients with decompensated cirrhosis are fatigue, anemia, nausea, headache, insomnia and diarrhea.
(6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
---------------------------------DRUG INTERACTIONS--------------------------•
P-gp inducers and/or moderate to potent CYP inducers (e.g., rifampin, St. John’s wort, carbamazepine): May decrease concentrations of sofosbuvir and/or velpatasvir. Use of EPCLUSA with P-gp inducers and/or moderate to potent CYP inducers is not recommended (5.2, 7)
•
Consult the full prescribing inform
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Serious Symptomatic Bradycardia When Sofosbuvir Is Coadministered with
Amiodarone and Another HCV Direct Acting Antiviral
Advise patients to seek medical evaluation immediately for symptoms of
bradycardia such as near-fainting or fainting, dizziness or lightheadedness,
malaise, weakness, excessive tiredness, shortness of breath, chest pain,
confusion or memory problems
.
Drug Interactions
Inform patients that EPCLUSA may interact with other drugs. Advise patients to
report to their healthcare provider the use of any other prescription or
nonprescription medication or herbal products including St. John’s wort.
Administration
Advise patients to take EPCLUSA once daily on a regular dosing schedule with or
without food. Inform patients that it is important not to miss or skip doses and to
take EPCLUSA for the duration that is recommended by the physician.
Pregnancy
Advise patients to avoid pregnancy during combination treatment with EPCLUSA
and ribavirin and for 6 months after completion of treatment. Inform patients to notify
their healthcare provider immediately in the event of a pregnancy..
Manufactured and distributed by:
Gilead Sciences, Inc.
Foster City, CA 94404
EPCLUSA, COMPLERA, GENVOYA, HARVONI, and STRIBILD are trademarks of
Gilead Sciences, Inc., or its related companies. ATRIPLA is a trademark of BristolMyers
Squibb & Gilead Sciences, LLC. All other trademarks referenced herein are the
property of their respective owners.
© 2016 Gilea
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
EPCLUSA is a fixed-dose combination of sofosbuvir and velpatasvir which are
direct-acting antiviral agents against the hepatitis C virus.
2. Pharmacokinetics
The pharmacokinetic properties of the components of EPCLUSA are provided in Table 3.
The multiple dose pharmacokinetic parameters of sofosbuvir and its metabolite,
GS-331007, and velpatasvir are provided in Table
Table Pharmacokinetic Properties of the Components of EPCLUSA
Sofosbuvir Velpatasvir
Absorption
Tmax (h) 0.5.1 3
Effect of moderate meal (relative to fasting) >60% > 34%
Effect of high fat meal (relative to fasting) > 78% > 21%
Distribution
% Bound to human plasma proteins 61-65 >99.5
61-65
Blood-to-plasma ratio 0.7 0.52-0.67
Metabolism
Metabolism Cathepsin A CYP2B6
CES1 HINT1 CYP2C8
CYP3A4
Elimination
Major route of elimination SOF: Biliary
metabolism excretion
GS-331007b as parent
glomerular (77%)
filtration and
active tubular
sectretion
t1/2 (h)c SOF: 0.5 15
% Of dose excreted in urine 80 0.4
% Of dose excreted in feces 14 94
Notes
CES1 = carboxylesterase 1; HINT1 = histidine triad nucleotide-binding protein 1
Values refer to mean systemic exposure.
Moderate meal = ~600 kcal, 30% fat;
high fat meal = ~800 kcal, 50% fat.
EPCLUSA can be taken with or without food.
GS-331007 is the primary circulating nucleoside metabolite of SOF.
.
t1/2 values refer to median terminal plasma half-life.
.
Single dose administration of [14C] SOF or [14C] VEL in mass balance studies.
.
Predominantly as GS-331007.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Risk Summary
If EPCLUSA is administered with ribavirin, the combination regimen is contraindicated in
pregnant women and in men whose female partners are pregnant. Refer to the ribavirin
prescribing information for more information on ribavirin-associated risks of use during
pregnancy
2. Lactation
Risk Summary
It is not known whether the components of EPCLUSA and its metabolites are
present in human breast milk, affect human milk production, or have effects
on the breastfed infant.
The predominant circulating metabolite of sofosbuvir (GS-331007) was the
primary component observed in the milk of lactating rats administered
sofosbuvir, without effect on nursing pups.
When administered to lactating rats, velpatasvir was detected in the milk of
lactating rats and in the plasma of nursing pups without effects on the
nursing pups .
3. Pediatric Use
Safety and effectiveness of EPCLUSA have not been established in pediatric
patients.
4. Geriatric Use
Clinical trials of EPCLUSA included 156 subjects aged 65 and over (12% of total
number of subjects in the Phase 3 clinical trials).
No overall differences in safety or effectiveness were observed between these
subjects and younger subjects, and other reported clinical experience has not
identified differences in responses between the elderly and younger patients,
but greater sensitivity of some older individuals cannot be ruled out.
No dosage adjustment of EPCLUSA is warranted in geriatric patients.
.
5.Renal Impairment
No dosage adjustment of EPCLUSA is required for patients with mild or moderate
renal impairment.
The safety and efficacy of EPCLUSA have not been established in patients with
severe renal impairment (eGFR less than 30 mL/min/1.73 m2 ) or ESRD requiring
hemodialysis. No dosage recommendation can be given for patients with severe renal
impairment or ESRD.
Refer to ribavirin prescribing information regarding use of ribavirin in patients
with renal impairment.
6. Hepatic Impairment
No dosage adjustment of EPCLUSA is required for patients with mild, moderate, or
severe hepatic impairment (Child-Pugh Class A, B, or C) ,
Clinical and hepatic laboratory monitoring (including direct bilirubin), as clinically
indicated, is recommended for patients with decompensated cirrhosis receiving
treatment with EPCLUSA and ribavirin.
