Approved Drug Label (PDF)
Boxed Warning
Newly added section
WARNING: RISKS OF HEPATOTOXICITY
Hepatotoxicity has occurred
with the use of VEOZAH
in the postmarketing setting (5.1).
- Perform
hepatic laboratory tests prior to initiation of treatment to evaluate for
hepatic function and injury. Do not start VEOZAH
if either aminotransferase is greater than or equal to 2 x the upper limit of normal (ULN) or if the total bilirubin is greater than or equal to 2 x ULN for the
evaluating laboratory.
- Perform follow-up
hepatic laboratory testing
monthly for the first 3 months, at 6 months,
and 9 months of treatment (2.1, 5.1).
- Advise
patients to discontinue VEOZAH immediately and seek medical attention including
hepatic laboratory tests if they experience signs or symptoms
that may suggest
liver injury (new onset fatigue, decreased appetite, nausea,
vomiting, pruritus, jaundice, pale feces, dark urine, or abdominal pain) (2.1, 5.1).
- Discontinue VEOZAH
if transaminase elevations are > 5 x ULN, or if transaminase elevations are > 3 x ULN and the total bilirubin
level is > 2 x ULN.
If transaminase elevations > 3 x ULN occur, perform
more frequent follow-up hepatic laboratory tests until resolution (5.1).
5
Warnings and Precautions
5.1 Hepatotoxicity
Subsection title revised
Additions and/or
revisions underlined:
In
three clinical trials, elevations in serum transaminase [alanine
aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels greater
than or equal to 3 x the upper limit of normal (ULN) occurred in 2.3% [exposure adjusted incidence rate (EAIR) of 2.7 per 100 person-years]
of women receiving VEOZAH and 0.9% (EAIR of 1.5 per 100 person-years) of women
receiving placebo. No elevations in serum total bilirubin (greater than or
equal to 2 x ULN) occurred. Women with ALT or AST elevations were generally
asymptomatic. Transaminase levels returned to pretreatment levels (or close to
these) without sequelae with dose continuation, and upon dose interruption, or
discontinuation. Women with cirrhosis were not studied [see Adverse Reactions (6.1)].
In
the postmarketing setting, cases of drug-induced liver injury with
elevations of ALT, AST, alkaline phosphatase (ALP), and total bilirubin occurred within 40 days of starting VEOZAH.
Patients reported a general sense of feeling unwell and
symptoms of fatigue, nausea, pruritus, jaundice, pale feces, and dark urine. The
patients’ signs and symptoms gradually resolved after discontinuation of
VEOZAH [see Adverse Reactions (6.2)].
Perform baseline
hepatic laboratory tests to evaluate
for hepatic function
and injury [including serum ALT, serum AST,
serum ALP, and serum bilirubin (total and direct)] prior to VEOZAH initiation.
Do not start VEOZAH if ALT or AST is greater than or equal to 2 x ULN or if the
total bilirubin is greater than or equal to 2 x ULN for the evaluating
laboratory.
Perform follow-up hepatic laboratory tests monthly for the first 3 months,
at 6 months, and 9 months after initiation of therapy.
Advise patients
to discontinue VEOZAH immediately and seek medical
attention including hepatic
laboratory tests if they experience signs or symptoms that
may suggest liver injury:
- new onset fatigue, decreased appetite, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or abdominal pain.
Discontinue VEOZAH
if:
- transaminase elevations are greater than or
equal to 5 x ULN.
- transaminase elevations are greater than or equal to 3 x ULN and total
bilirubin is greater than or equal to 2
x ULN.
If transaminase elevations greater
than or equal to 3 x ULN occur,
perform more frequent
follow-up hepatic laboratory tests until resolution.
Exclude alternative causes of hepatic
laboratory test elevations.
6
Adverse Reactions
6.1 Clinical
Trials Experience
Additions and/or
revisions underlined:
…
In
the pooled laboratory data of Trials 1, 2, and 3, elevated hepatic
transaminases (greater than or equal to 3 x ULN) occurred in 25 women
(2.3%, 2.7 EAIR) exposed to VEOZAH 45 mg (n=1100,
912.1 total person-years) as compared to 8 women (0.9%, 1.5 EAIR) exposed to placebo (n=952, 549.1
total person-years).
6.2 Postmarketing
Experience
Additions and/or revisions underlined:
The following adverse reactions have been identified during postapproval use of VEOZAH.
Because these 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.
Hepatic: Cases of serious drug-induced hepatotoxicity occurred within
40 days of starting VEOZAH.
Patients experienced elevated
transaminases (up to 50 x ULN at peak elevation), elevated alkaline
phosphatase (up to 4 x ULN at peak elevation), and bilirubin (up to 5
x ULN at peak elevation) coupled with symptoms of fatigue, nausea,
pruritus, jaundice, pale feces, and dark urine. After discontinuation of
VEOZAH, these abnormalities gradually resolved.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or
revisions underlined:
Advise patients
to read the FDA-approved patient
labeling (Patient Information).
Evaluation of Hepatic Injury During Treatment
with VEOZAH
Inform
patients that they will have to have a blood test to evaluate their liver
function before beginning VEOZAH and while using VEOZAH monthly for the first 3
months, at 6 months, and 9 months after initialization of therapy. Advise
patients to discontinue VEOZAH immediately and seek medical attention including
hepatic laboratory tests if they experience signs or symptoms that may suggest
liver abnormalities such as new onset fatigue,
decreased appetite, nausea, vomiting, pruritus, jaundice,
pale feces, dark urine, or abdominal pain [see Warnings and Precautions (5.1)].
…
PATIENT INFORMATION
Additions and/or
revisions underlined:
What is the most important information I should know about VEOZAH?
…
Stop
VEOZAH right away and call your healthcare provider if you have the following signs
or symptoms of liver problems:
feeling more tired than you do
usually
yellowing of the eyes or skin (jaundice)
decreased appetite
pale feces
nausea
dark urine
vomiting
pain in the stomach
(abdomen)
itching
See “What are the possible
side effects of VEOZAH?” for more information about side effects.
…
What are the
possible side effects of VEOZAH?
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Hepatic Transaminase Elevation and Hepatotoxicity
Subsection
title revised
Additions
and/or revisions underlined:
…
In
the postmarketing setting, a case of acute mixed hepatocellular cholestatic
drug-induced liver injury with elevations of ALT, AST, alkaline phosphatase
(ALP), and total bilirubin with symptoms of fatigue, nausea, pruritus,
jaundice, pale feces, and dark urine occurred in a woman receiving VEOZAH. The
individual’s signs and symptoms gradually resolved after discontinuation of the
drug [see Adverse Reactions (6.2)].
Perform
baseline hepatic laboratory tests to evaluate for hepatic function and
injury [including serum alanine aminotransferase (ALT), serum aspartate
aminotransferase (AST), serum alkaline phosphatase (ALP), and serum
bilirubin (total and direct)] prior to VEOZAH initiation. Do not start VEOZAH
if the concentration of ALT or AST is equal to or exceeds 2 times the ULN or if
the total bilirubin is elevated (for example, equal to or exceeds 2 times the
ULN) for the evaluating laboratory. If baseline hepatic transaminase evaluation
is less than 2 times the ULN and the total bilirubin is normal, VEOZAH can be
started.
Perform
follow-up hepatic laboratory tests monthly for the first 3 months, at 6
months, and 9 months after initiation of therapy.
Advise
patients to discontinue VEOZAH immediately and seek medical attention including
hepatic laboratory tests if they experience signs or symptoms that may suggest
liver injury:
- new onset fatigue, nausea, vomiting, pruritus,
jaundice, pale feces, dark urine, or right upper quadrant pain.
Discontinue
VEOZAH if:
- transaminase elevations are greater than 3 times the
ULN and the total bilirubin level is greater than 2 times the ULN.
If
transaminase elevations greater than 3 times the ULN occur, perform more
frequent follow-up hepatic laboratory tests until resolution.
Exclude
alternative causes of hepatic laboratory test elevations.
6
Adverse Reactions
Addition of the
following to the bulleted line listing:
The
following serious adverse reactions are discussed elsewhere in the labeling:
- Hepatic
Transaminase Elevation and Hepatotoxicity [see
Warnings and Precautions (5.1)].
6.2 Postmarketing
Experience
Newly added
subsection:
The
following adverse reactions have been identified during postapproval use of
VEOZAH. Because these 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.
Hepatic: A case of
serious drug-induced hepatotoxicity with elevated transaminases (greater than
10 times the ULN at peak elevation), elevated alkaline phosphatase (greater
than 4 times the ULN at peak elevation), and bilirubin (greater than 3 times
the ULN at peak elevation) coupled with symptoms of fatigue, nausea, pruritus,
jaundice, pale feces, and dark urine occurred within 40 days of starting
VEOZAH. After discontinuation of VEOZAH, these abnormalities gradually
resolved.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined:
Evaluation
of Hepatic Injury During Treatment with VEOZAH
Inform
patients that they will have to have a blood test to evaluate their liver function
before beginning VEOZAH and while using VEOZAH monthly for the first 3
months, at 6 months, and 9 months after initialization of therapy.
Advise patients to discontinue VEOZAH immediately and seek medical
attention including hepatic laboratory tests if they experience signs or
symptoms that may suggest liver abnormalities such as new onset
fatigue, nausea, vomiting, pruritus, jaundice, pale feces, dark
urine, or right upper quadrant pain [see Warnings and Precautions (5.1)].
Serious
Adverse Reactions with VEOZAH
Inform
patients of possible serious adverse reactions of VEOZAH including hepatic
transaminase elevation and liver injury [see Warnings and Precautions (5.1)].
PATIENT
INFORMATION
Additions and/or revisions underlined:
What
are the possible side effects of VEOZAH? VEOZAH can cause serious side effects,
including:
- increased liver blood test values and liver
problems. Your healthcare provider will do a blood test to
check your liver before you start taking VEOZAH. Your healthcare provider will
also do this blood test monthly for the first 3 months, at month 6, and
month 9 after you start taking VEOZAH or if you have signs or symptoms that
suggest liver problems. If your liver blood test values are elevated, your
healthcare provider may advise you to stop treatment or request additional
liver blood tests.
Stop
VEOZAH and
call your healthcare provider right away if you have the following signs or
symptoms of liver problems:
feeling more tired than you
do usually
nausea
vomiting
itching
yellowing of the eyes or skin (jaundice)
pale feces
dark urine
pain in the right upper stomach (abdomen)