Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease
(newly added subsection)
Postmarketing cases of hepatic
decompensation/failure, including
those with fatal outcomes,
have been reported
in patients
treated with HCV NS3/4A protease
inhibitor- containing regimens, including treatment with VOSEVI.
Reported cases occurred in patients with
baseline cirrhosis with and without
moderate or severe liver impairment (Child-Pugh
B or C). Because these
events are reported voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency
or establish
a causal
relationship to drug exposure.
In patients
with compensated cirrhosis (Child-Pugh A) or evidence of
advanced liver disease such as portal hypertension, perform hepatic laboratory
testing as clinically indicated;
and monitor for signs and symptoms
of hepatic
decompensation such as the presence
of jaundice, ascites, hepatic encephalopathy,
and variceal hemorrhage.
Discontinue VOSEVI in
patients who develop evidence
of hepatic decompensation/failure.
VOSEVI is not recommended
in
patients with moderate
to severe hepatic impairment (Child-Pugh B or C)
or those
with any history of prior
hepatic decompensation.
6
Adverse Reactions
6.2 Postmarketing Experience
(additions and/or
revisions are underlined)
The following adverse reactions have been identified
during post approval use of sofosbuvir-containing regimens. Because postmarketing
reactions are reported voluntarily
from a population of uncertain size, it is not
always possible to reliably
estimate their frequency
or establish
a causal relationship to drug exposure.
Hepatobiliary Disorders
Hepatic decompensation,
hepatic failure with NS3/4A protease
inhibitor-containing regimens.
Cardiac Disorders
Serious symptomatic
bradycardia has been reported in
patients taking amiodarone who initiated treatment with a sofosbuvir-containing regimen.
Skin and Subcutaneous Tissue Disorders
Skin rashes, sometimes
with blisters or angioedema-like
swelling Angioedema
7
Drug Interactions
7.3 Established and Potentially Significant Drug Interactions
(additions and/or
revisions are underlined)
Clearance of HCV
infection with direct acting antivirals
may lead to changes in hepatic
function, which may
impact the safe and effective use of concomitant
medications. For example,
altered blood glucose control
resulting in serious symptomatic hypoglycemia has been
reported in diabetic patients in
postmarketing case reports and
published epidemiological studies. Management
of
hypoglycemia in
these cases required either discontinuation or dose modification of concomitant medications used for diabetes treatment.
Frequent monitoring of relevant laboratory
parameters (e.g. 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 (e.g. certain immunosuppressants) is recommended to ensure safe
and effective use. Dose adjustments
of
concomitant medications may be necessary.
8
Use in Specific Populations
8.7 Hepatic Impairment
(additions and/or
revisions are underlined)
No
dosage adjustment of VOSEVI is
required for patients with mild
hepatic impairment (Child-Pugh A). VOSEVI is not
recommended in patients with moderate
or severe hepatic
impairment (Child-Pugh B or C)
due to the higher exposures of voxilaprevir (up to
6-fold in non-HCV infected subjects); the safety and efficacy have not been established in HCV-infected patients with moderate or
severe hepatic impairment. Postmarketing cases
of hepatic
decompensation/failure have been
reported in these patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(additions and/or
revisions are underlined)
Advise the patient
to read the FDA-approved patient labeling
(Patient Information).
Risk of Hepatitis B Virus Reactivation in Patients
Coinfected with HCV and HBV Inform patients that
HBV reactivation can occur in
patients coinfected with HBV during
or after treatment of HCV virus infection. Advise patients
to tell their healthcare provider
if they have a history of
hepatitis B infection.
Riskr of Hepatic Decompensation/Failure
in
Patients with Evidence
of
Advanced Liver Disease
Advise patients to seek medical evaluation immediately for symptoms
of worsening
liver problems such as
nausea, tiredness, yellowing of the
skin or white part of
the eyes, bleeding or bruising
more easily than normal, confusion,
loss of appetite, diarrhea, dark or brown
urine, dark or bloody stool, swelling of the
stomach area (abdomen) or pain in the
upper right side of the stomach
area, sleepiness, or vomiting of
blood.
PATIENT INFORMATION
(additions and/or
revisions are underlined)
What
are the possible side effects of VOSEVI? VOSEVI may cause serious side effects, including:
Hepatitis B virus (HBV) reactivation. See “What is the most important information I should know about VOSEVI?”
In people who had or have advanced liver problems before starting
treatment with VOSEVI:
rare risk of worsening
liver problems, liver failure and death.
Your healthcare provider will check you
for signs and symptoms of worsening liver problems during
treatment with VOSEVI. Tell your
healthcare provider right away if you have any of the following signs
and symptoms:
nausea
diarrhea
tiredness
dark or brown (tea-colored) urine
yellowing of your skin
or white part of your
eyes
swelling of your stomach
area (abdomen) or pain on the upper right side of your stomach area
bleeding or bruising more easily than normal
sleepiness
confusion
vomiting of blood
dark, black, or bloody stool
lightheadedness
loss of appetite
Slow heart rate
(bradycardia). VOSEVI treatment may result in slowing of the heart rate along with other symptoms when taken with amiodarone (Cordarone®, Nexterone®, Pacerone®), a medicine
used to treat certain heart problems.
In some cases, bradycardia
has led to death or the need for a
heart pacemaker when amiodarone is
taken with medicines similar to VOSEVI
that contain sofosbuvir. Get medical help right away if you take amiodarone with VOSEVI and get any of the
following symptoms:
The most common side effects of VOSEVI include
headache, tiredness, diarrhea, and
nausea.
These are not all the possible side effects of VOSEVI.
Call your doctor
for medical advice about side effects. You may
report side effects to FDA at 1-800-
FDA-1088.
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