Approved Drug Label (PDF)
5
Warnings and Precautions
5.1
Diarrhea
(Additions and/or revisions underlined)
Severe diarrhea associated
with dehydration and infection occurred in patients treated with
VERZENIO.
Across four clinical trials
in 3691 patients, diarrhea occurred in 81% to 90% of patients who
received VERZENIO. Grade 3 diarrhea occurred in 8% to 20% of
patients receiving VERZENIO [see
Adverse Reactions (6.1)].
Most patients experienced
diarrhea during the first month of VERZENIO treatment. The median
time to onset of the first diarrhea event ranged from 6 to 8 days; and
the median duration of Grade 2 and Grade 3 diarrhea ranged from 6 to
11 days and 5 to 8 days, respectively. Across trials, 19% to
26% of patients with diarrhea required a VERZENIO dose interruption
and 13% to 23% required a dose reduction.
Instruct patients to
start antidiarrheal therapy such as loperamide at the first sign of loose
stools, increase oral fluids, and notify their healthcare provider for
further instructions and appropriate follow up [see Patient Counseling Information (17)]. For Grade 3 or 4
diarrhea, or diarrhea that requires hospitalization, discontinue VERZENIO until
toxicity resolves to less than or equal to Grade 1, and then resume
VERZENIO at the next lower dose [see
Dosage and Administration (2.3)].
5.2
Neutropenia
(Additions and/or revisions underlined)
Neutropenia, including febrile
neutropenia and fatal neutropenic sepsis, occurred in patients treated
with VERZENIO.
Across four clinical trials
in 3691 patients, neutropenia occurred in a 37% to 46% of patients receiving
VERZENIO. A Grade greater than or equal to 3 decrease in neutrophil count
(based on laboratory findings) occurred in 19% to 32% of patients
receiving VERZENIO. Across trials, the median time to the first
episode of Grade greater than or equal to 3 neutropenia ranged from 29 days
to 33 days, and the median duration of Grade greater than or equal
to 3 neutropenia ranged from 11 days to 16 days [see Adverse Reactions (6.1)].
Febrile neutropenia has been
reported in <1% of patients exposed to VERZENIO across trials. Two deaths
due to neutropenic sepsis were observed in MONARCH 2. Inform patients to
promptly report any episodes of fever to their healthcare provider [see Patient Counseling Information (17)].
5.3
Interstitial Lung Disease (ILD) or Pneumonitis
(Additions and/or revisions underlined)
Severe, life-threatening, or fatal
interstitial lung disease (ILD) or pneumonitis can occur in patients treated
with VERZENIO and other CDK4/6 inhibitors. In VERZENIO-treated patients in
early breast cancer (monarchE, N=2791), 3% of patients experienced ILD or
pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one fatality
(0.1%). In VERZENIO- treated patients in advanced or metastatic breast cancer (N=900)
(MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of VERZENIO-treated patients had ILD
or pneumonitis of any grade: 0.6% had Grade 3 or 4, and 0.4% had fatal
outcomes. Additional cases of ILD or pneumonitis have been observed in
the postmarketing setting, with fatalities reported [see Adverse Reactions (6.2)].
5.4
Hepatotoxicity
(Additions and/or revisions underlined)
Grade greater than or equal to 3 ALT (2% to 6%) and
AST (2% to 3%) were reported in
patients receiving VERZENIO.
Across three clinical trials in 3559 patients
(monarchE, MONARCH 2, MONARCH 3), the median time to onset of Grade greater
than or equal to 3 ALT increases ranged from 57 to 87 days and the median time
to resolution to Grade <3 was 13 to 14 days. The median time to onset of
Grade greater than or equal to 3 AST increases ranged from 71 to 185 days and
the median time to resolution to Grade less than 3 ranged from 11 to 15 days.
Monitor liver function tests
(LFTs) prior to the start of VERZENIO therapy, every 2 weeks for the first 2
months, monthly for the next 2 months, and as clinically indicated. Dose
interruption, dose reduction, dose discontinuation, or delay in starting
treatment cycles is recommended for patients who develop persistent or
recurrent Grade 2, or any Grade 3 or Grade 4 hepatic transaminase
elevation [see Dosage and Administration
(2.3)].
5.5
Venous Thromboembolism
(Additions and/or revisions underlined)
Across three clinical trials in 3559
patients (monarchE, MONARCH 2, MONARCH 3), venous thromboembolic events
were reported in 2% to 5% of patients treated with VERZENIO. Venous
thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic
venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary
vein thrombosis, and inferior vena cava thrombosis. In clinical trials,
deaths due to venous thromboembolism have been reported in patients treated
with VERZENIO.
VERZENIO has not been studied in
patients with early breast cancer who had a history of venous thromboembolism.
Monitor patients for signs and symptoms of venous thrombosis and pulmonary
embolism and treat as medically appropriate. Dose interruption is
recommended for early breast cancer patients with any grade venous
thromboembolic event and for advanced or metastatic breast cancer patients with
a Grade 3 or 4 venous thromboembolic event [see
Dosage and Administration (2.3)].
6
Adverse Reactions
6.1
Clinical Studies Experience
(Extensive
changes; please refer to label)
8
Use in Specific Populations
8.3
Females and Males of Reproductive Potential
(Additions and/or revisions underlined)
Based on animal studies, VERZENIO can
cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy
Testing
Verify
pregnancy status in females of reproductive potential prior to initiating
treatment with VERZENIO.
8.5
Geriatric Use
(Additions and/or revisions underlined)
Of the 2791 VERZENIO-treated
patients in monarchE, 15% were 65 years of age or older and 2.7% were 75 years
of age or older.
Of the 900 patients who received VERZENIO in MONARCH 1,
MONARCH 2, and MONARCH 3, 38% were 65 years of age or older and 10% were 75
years of age or older.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17
PATIENT COUNSELING INFORMATION
(Additions and/or revisions underlined)
Embryo-Fetal Toxicity
Advise pregnant
women and females of reproductive potential of the potential risk to a
fetus. Advise females to inform their healthcare provider of a known or
suspected pregnancy [see Warnings and
Precautions (5.6) and Use in Specific Populations (8.1)].
Advise females of reproductive potential to use effective contraception
during VERZENIO treatment and for 3 weeks after the last dose [see Use in Specific Populations (8.1, 8.3)].
Lactation
Advise lactating women not to breastfeed
during VERZENIO treatment and for at least 3 weeks after the last dose [see Use in Specific Populations (8.2)].
Infertility
Inform males of reproductive potential
that VERZENIO may impair fertility [see
Use in Specific Populations (8.3)].
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1
Diarrhea
(Additions and/or revisions underlined)
Severe diarrhea associated
with dehydration and infection occurred in patients treated with
VERZENIO.
Across four clinical trials
in 3691 patients, diarrhea occurred in 81% to 90% of patients who
received VERZENIO. Grade 3 diarrhea occurred in 8% to 20% of
patients receiving VERZENIO [see
Adverse Reactions (6.1)].
Most patients experienced
diarrhea during the first month of VERZENIO treatment. The median
time to onset of the first diarrhea event ranged from 6 to 8 days; and
the median duration of Grade 2 and Grade 3 diarrhea ranged from 6 to
11 days and 5 to 8 days, respectively. Across trials, 19% to
26% of patients with diarrhea required a VERZENIO dose interruption
and 13% to 23% required a dose reduction.
Instruct patients to
start antidiarrheal therapy such as loperamide at the first sign of loose
stools, increase oral fluids, and notify their healthcare provider for
further instructions and appropriate follow up [see Patient Counseling Information (17)]. For Grade 3 or 4
diarrhea, or diarrhea that requires hospitalization, discontinue VERZENIO until
toxicity resolves to less than or equal to Grade 1, and then resume
VERZENIO at the next lower dose [see
Dosage and Administration (2.3)].
5.2
Neutropenia
(Additions and/or revisions underlined)
Neutropenia, including febrile
neutropenia and fatal neutropenic sepsis, occurred in patients treated
with VERZENIO.
Across four clinical trials
in 3691 patients, neutropenia occurred in a 37% to 46% of patients receiving
VERZENIO. A Grade greater than or equal to 3 decrease in neutrophil count
(based on laboratory findings) occurred in 19% to 32% of patients
receiving VERZENIO. Across trials, the median time to the first
episode of Grade greater than or equal to 3 neutropenia ranged from 29 days
to 33 days, and the median duration of Grade greater than or equal
to 3 neutropenia ranged from 11 days to 16 days [see Adverse Reactions (6.1)].
Febrile neutropenia has been
reported in <1% of patients exposed to VERZENIO across trials. Two deaths
due to neutropenic sepsis were observed in MONARCH 2. Inform patients to
promptly report any episodes of fever to their healthcare provider [see Patient Counseling Information (17)].
5.3
Interstitial Lung Disease (ILD) or Pneumonitis
(Additions and/or revisions underlined)
Severe, life-threatening, or fatal
interstitial lung disease (ILD) or pneumonitis can occur in patients treated
with VERZENIO and other CDK4/6 inhibitors. In VERZENIO-treated patients in
early breast cancer (monarchE, N=2791), 3% of patients experienced ILD or
pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one fatality
(0.1%). In VERZENIO- treated patients in advanced or metastatic breast cancer (N=900)
(MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of VERZENIO-treated patients had ILD
or pneumonitis of any grade: 0.6% had Grade 3 or 4, and 0.4% had fatal
outcomes. Additional cases of ILD or pneumonitis have been observed in
the postmarketing setting, with fatalities reported [see Adverse Reactions (6.2)].
5.4
Hepatotoxicity
(Additions and/or revisions underlined)
Grade greater than or equal to 3 ALT (2% to 6%) and
AST (2% to 3%) were reported in
patients receiving VERZENIO.
Across three clinical trials in 3559 patients
(monarchE, MONARCH 2, MONARCH 3), the median time to onset of Grade greater
than or equal to 3 ALT increases ranged from 57 to 87 days and the median time
to resolution to Grade <3 was 13 to 14 days. The median time to onset of
Grade greater than or equal to 3 AST increases ranged from 71 to 185 days and
the median time to resolution to Grade less than 3 ranged from 11 to 15 days.
Monitor liver function tests
(LFTs) prior to the start of VERZENIO therapy, every 2 weeks for the first 2
months, monthly for the next 2 months, and as clinically indicated. Dose
interruption, dose reduction, dose discontinuation, or delay in starting
treatment cycles is recommended for patients who develop persistent or
recurrent Grade 2, or any Grade 3 or Grade 4 hepatic transaminase
elevation [see Dosage and Administration
(2.3)].
5.5
Venous Thromboembolism
(Additions and/or revisions underlined)
Across three clinical trials in 3559
patients (monarchE, MONARCH 2, MONARCH 3), venous thromboembolic events
were reported in 2% to 5% of patients treated with VERZENIO. Venous
thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic
venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary
vein thrombosis, and inferior vena cava thrombosis. In clinical trials,
deaths due to venous thromboembolism have been reported in patients treated
with VERZENIO.
VERZENIO has not been studied in
patients with early breast cancer who had a history of venous thromboembolism.
Monitor patients for signs and symptoms of venous thrombosis and pulmonary
embolism and treat as medically appropriate. Dose interruption is
recommended for early breast cancer patients with any grade venous
thromboembolic event and for advanced or metastatic breast cancer patients with
a Grade 3 or 4 venous thromboembolic event [see
Dosage and Administration (2.3)].
6
Adverse Reactions
6.1
Clinical Studies Experience
(Extensive
changes; please refer to label)
8
Use in Specific Populations
8.3
Females and Males of Reproductive Potential
(Additions and/or revisions underlined)
Based on animal studies, VERZENIO can
cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy
Testing
Verify
pregnancy status in females of reproductive potential prior to initiating
treatment with VERZENIO.
8.5
Geriatric Use
(Additions and/or revisions underlined)
Of the 2791 VERZENIO-treated
patients in monarchE, 15% were 65 years of age or older and 2.7% were 75 years
of age or older.
Of the 900 patients who received VERZENIO in MONARCH 1,
MONARCH 2, and MONARCH 3, 38% were 65 years of age or older and 10% were 75
years of age or older.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17
PATIENT COUNSELING INFORMATION
(Additions and/or revisions underlined)
Embryo-Fetal Toxicity
Advise pregnant
women and females of reproductive potential of the potential risk to a
fetus. Advise females to inform their healthcare provider of a known or
suspected pregnancy [see Warnings and
Precautions (5.6) and Use in Specific Populations (8.1)].
Advise females of reproductive potential to use effective contraception
during VERZENIO treatment and for 3 weeks after the last dose [see Use in Specific Populations (8.1, 8.3)].
Lactation
Advise lactating women not to breastfeed
during VERZENIO treatment and for at least 3 weeks after the last dose [see Use in Specific Populations (8.2)].
Infertility
Inform males of reproductive potential
that VERZENIO may impair fertility [see
Use in Specific Populations (8.3)].
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1
Diarrhea
(Additions and/or revisions underlined)
Severe diarrhea associated
with dehydration and infection occurred in patients treated with
VERZENIO.
Across four clinical trials
in 3691 patients, diarrhea occurred in 81% to 90% of patients who
received VERZENIO. Grade 3 diarrhea occurred in 8% to 20% of
patients receiving VERZENIO [see
Adverse Reactions (6.1)].
Most patients experienced
diarrhea during the first month of VERZENIO treatment. The median
time to onset of the first diarrhea event ranged from 6 to 8 days; and
the median duration of Grade 2 and Grade 3 diarrhea ranged from 6 to
11 days and 5 to 8 days, respectively. Across trials, 19% to
26% of patients with diarrhea required a VERZENIO dose interruption
and 13% to 23% required a dose reduction.
Instruct patients to
start antidiarrheal therapy such as loperamide at the first sign of loose
stools, increase oral fluids, and notify their healthcare provider for
further instructions and appropriate follow up [see Patient Counseling Information (17)]. For Grade 3 or 4
diarrhea, or diarrhea that requires hospitalization, discontinue VERZENIO until
toxicity resolves to less than or equal to Grade 1, and then resume
VERZENIO at the next lower dose [see
Dosage and Administration (2.3)].
5.2
Neutropenia
(Additions and/or revisions underlined)
Neutropenia, including febrile
neutropenia and fatal neutropenic sepsis, occurred in patients treated
with VERZENIO.
Across four clinical trials
in 3691 patients, neutropenia occurred in a 37% to 46% of patients receiving
VERZENIO. A Grade greater than or equal to 3 decrease in neutrophil count
(based on laboratory findings) occurred in 19% to 32% of patients
receiving VERZENIO. Across trials, the median time to the first
episode of Grade greater than or equal to 3 neutropenia ranged from 29 days
to 33 days, and the median duration of Grade greater than or equal
to 3 neutropenia ranged from 11 days to 16 days [see Adverse Reactions (6.1)].
Febrile neutropenia has been
reported in <1% of patients exposed to VERZENIO across trials. Two deaths
due to neutropenic sepsis were observed in MONARCH 2. Inform patients to
promptly report any episodes of fever to their healthcare provider [see Patient Counseling Information (17)].
5.3
Interstitial Lung Disease (ILD) or Pneumonitis
(Additions and/or revisions underlined)
Severe, life-threatening, or fatal
interstitial lung disease (ILD) or pneumonitis can occur in patients treated
with VERZENIO and other CDK4/6 inhibitors. In VERZENIO-treated patients in
early breast cancer (monarchE, N=2791), 3% of patients experienced ILD or
pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one fatality
(0.1%). In VERZENIO- treated patients in advanced or metastatic breast cancer (N=900)
(MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of VERZENIO-treated patients had ILD
or pneumonitis of any grade: 0.6% had Grade 3 or 4, and 0.4% had fatal
outcomes. Additional cases of ILD or pneumonitis have been observed in
the postmarketing setting, with fatalities reported [see Adverse Reactions (6.2)].
5.4
Hepatotoxicity
(Additions and/or revisions underlined)
Grade greater than or equal to 3 ALT (2% to 6%) and
AST (2% to 3%) were reported in
patients receiving VERZENIO.
Across three clinical trials in 3559 patients
(monarchE, MONARCH 2, MONARCH 3), the median time to onset of Grade greater
than or equal to 3 ALT increases ranged from 57 to 87 days and the median time
to resolution to Grade <3 was 13 to 14 days. The median time to onset of
Grade greater than or equal to 3 AST increases ranged from 71 to 185 days and
the median time to resolution to Grade less than 3 ranged from 11 to 15 days.
Monitor liver function tests
(LFTs) prior to the start of VERZENIO therapy, every 2 weeks for the first 2
months, monthly for the next 2 months, and as clinically indicated. Dose
interruption, dose reduction, dose discontinuation, or delay in starting
treatment cycles is recommended for patients who develop persistent or
recurrent Grade 2, or any Grade 3 or Grade 4 hepatic transaminase
elevation [see Dosage and Administration
(2.3)].
5.5
Venous Thromboembolism
(Additions and/or revisions underlined)
Across three clinical trials in 3559
patients (monarchE, MONARCH 2, MONARCH 3), venous thromboembolic events
were reported in 2% to 5% of patients treated with VERZENIO. Venous
thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic
venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary
vein thrombosis, and inferior vena cava thrombosis. In clinical trials,
deaths due to venous thromboembolism have been reported in patients treated
with VERZENIO.
VERZENIO has not been studied in
patients with early breast cancer who had a history of venous thromboembolism.
Monitor patients for signs and symptoms of venous thrombosis and pulmonary
embolism and treat as medically appropriate. Dose interruption is
recommended for early breast cancer patients with any grade venous
thromboembolic event and for advanced or metastatic breast cancer patients with
a Grade 3 or 4 venous thromboembolic event [see
Dosage and Administration (2.3)].
6
Adverse Reactions
6.1
Clinical Studies Experience
(Extensive
changes; please refer to label)
8
Use in Specific Populations
8.3
Females and Males of Reproductive Potential
(Additions and/or revisions underlined)
Based on animal studies, VERZENIO can
cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy
Testing
Verify
pregnancy status in females of reproductive potential prior to initiating
treatment with VERZENIO.
8.5
Geriatric Use
(Additions and/or revisions underlined)
Of the 2791 VERZENIO-treated
patients in monarchE, 15% were 65 years of age or older and 2.7% were 75 years
of age or older.
Of the 900 patients who received VERZENIO in MONARCH 1,
MONARCH 2, and MONARCH 3, 38% were 65 years of age or older and 10% were 75
years of age or older.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17
PATIENT COUNSELING INFORMATION
(Additions and/or revisions underlined)
Embryo-Fetal Toxicity
Advise pregnant
women and females of reproductive potential of the potential risk to a
fetus. Advise females to inform their healthcare provider of a known or
suspected pregnancy [see Warnings and
Precautions (5.6) and Use in Specific Populations (8.1)].
Advise females of reproductive potential to use effective contraception
during VERZENIO treatment and for 3 weeks after the last dose [see Use in Specific Populations (8.1, 8.3)].
Lactation
Advise lactating women not to breastfeed
during VERZENIO treatment and for at least 3 weeks after the last dose [see Use in Specific Populations (8.2)].
Infertility
Inform males of reproductive potential
that VERZENIO may impair fertility [see
Use in Specific Populations (8.3)].
Approved Drug Label (PDF)
5
Warnings and Precautions
Interstitial Lung Disease (ILD)/Pneumonitis
Newly added
section:
Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or
pneumonitis can occur in patients
treated with VERZENIO and
other CDK 4/6
inhibitors. Across clinical trials (MONARCH 1, MONARCH 2, and MONARCH 3), 3.3% of VERZENIO-treated
patients had ILD/pneumonitis of any grade, 0.6% had Grade 3 or 4, and 0.4% had fatal outcomes.
Additional cases of
ILD/pneumonitis have been observed in the postmarketing setting, with
fatalities
reported.
Monitor patients for pulmonary
symptoms indicative of ILD/pneumonitis.
Symptoms may include hypoxia,
cough, dyspnea,
or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and
other causes for such symptoms
should be excluded by
means of appropriate investigations.
Dose interruption or dose reduction
is recommended
for patients who develop persistent
or recurrent
Grade 2 ILD/pneumonitis. Permanently discontinue VERZENIO in all
patients with Grade 3 or 4
ILD or pneumonitis.
6
Adverse Reactions
Newly added to
bulleted line listing:
·
Interstitial Lung
Disease (ILD)/Pneumonitis
Clinical Studies Experience
Additions and/or
revisions underlined:
Deaths due to adverse events
during treatment or during the 30-day
follow up were reported
in 2%
of patients. Cause of death in
these patients was due
to infection (2 patients)
or pneumonitis
(1 patient).
Postmarketing
Experience
Newly added
section:
The following adverse reactions have been identified during
post-approval use of VERZENIO. 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.
Respiratory
disorders: Interstitial lung disease (ILD)/pneumonitis.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Addition of the
following:
Interstitial Lung Disease/Pneumonitis
Advise patients to immediately report new or worsening
respiratory symptoms.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Diarrhea
(additions
underlined)
Diarrhea occurred in 81% of
patients receiving VERZENIO plus an aromatase inhibitor in MONARCH 3, 86%
of patients receiving VERZENIO plus fulvestrant in MONARCH 2, and 90% of
patients receiving VERZENIO alone in MONARCH 1. Grade 3 diarrhea occurred in 9%
of patients receiving VERZENIO plus an aromatase inhibitor in MONARCH 3,
13% of patients receiving VERZENIO plus fulvestrant in MONARCH 2, and in 20% of
patients receiving VERZENIO alone in MONARCH 1. Episodes of diarrhea have been
associated with dehydration and infection.
Diarrhea incidence was greatest
during the first month of VERZENIO dosing. In MONARCH 3, the median time to
onset of the first diarrhea event was 8 days, and the median duration of
diarrhea for Grades 2 and 3 were 11 and 8 days, respectively. In MONARCH 2, the
median time to onset of the first diarrhea event was 6 days, and the median
duration of diarrhea for Grades 2 and 3 were 9 days and 6 days, respectively. In
MONARCH 3, 19% of patients with diarrhea required a dose omission and 13%
required a dose reduction. In
MONARCH 2, 22% of patients with diarrhea required a dose omission and 22%
required a dose reduction. The time to onset and resolution for diarrhea
were similar across MONARCH 3, MONARCH 2, and MONARCH 1.
…
5.2 Neutropenia
(additions underlined)
Neutropenia occurred in 41% of patients receiving
VERZENIO plus an aromatase inhibitor in MONARCH 3, 46% of patients
receiving VERZENIO plus fulvestrant in MONARCH 2, and 37% of patients receiving
VERZENIO alone in MONARCH 1. A Grade greater than or equal to3 decrease in
neutrophil count (based on laboratory findings) occurred in 22% of patients
receiving VERZENIO plus an aromatase inhibitor in MONARCH 3, 32% of
patients receiving VERZENIO plus fulvestrant in MONARCH 2, and in 27% of
patients receiving VERZENIO in MONARCH 1. In MONARCH 3, the median time
to first episode of Grade greater than or equal to 3 neutropenia was 33
days, and in MONARCH 2 and MONARCH 1 was 29 days. In MONARCH 3,
median duration of Grade greater than or equal to 3 neutropenia was 11 days,
and for MONARCH 2 and MONARCH 1 was 15 days.
…
5.3 Hepatotoxicity
(additions underlined)
![]()
In
MONARCH 3, Grade greater than or equal to 3 increases in
ALT (6% versus 2%) and AST (3% versus 1%) were reported in the VERZENIO and
placebo arms, respectively. In MONARCH 2, Grade greater than or equal to 3
increases in ALT (4% versus 2%) and AST (2% versus 3%) were reported in the
VERZENIO and placebo arms, respectively.
![]()
In
MONARCH 3, for patients receiving VERZENIO plus an aromatase inhibitor with
Grade greater than or equal to 3 ALT increased, median time
to onset was 61 days, and median time to resolution to Grade <3 was 14 days.
In MONARCH 2, for patients receiving VERZENIO plus fulvestrant with Grade greater
than or equal to 3 ALT increased, median time to onset was 57 days, and median
time to resolution to Grade <3 was 14 days. In MONARCH 3, for patients
receiving VERZENIO plus an aromatase inhibitor with Grade greater than or
equal to 3 AST increased, median time to onset was 71 days, and median time
to resolution was 15 days. In MONARCH 2,
for patients receiving VERZENIO plus fulvestrant with Grade greater than or
equal to 3 AST increased, median time to onset was 185 days, and median time to
resolution was 13 days.
…
5.4 Venous Thromboembolism
(additions underlined)
![]()
![]()
In
MONARCH 3, venous thromboembolic events were reported in 5% of patients treated
with VERZENIO plus an aromatase inhibitor as compared to 0.6% of patients
treated with an aromatase inhibitor plus placebo. In
MONARCH 2, venous thromboembolic events were reported in 5% of patients treated
with VERZENIO plus fulvestrant as compared to 0.9% of patients treated with
fulvestrant plus placebo. Venous thromboembolic events included deep vein
thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral
venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior
vena cava thrombosis. Across the clinical development program, deaths due to
venous thromboembolism have been reported.
…
6
Adverse Reactions
6.1 Clinical Studies Experience
(extensive
additions, please refer to label)
7
Drug Interactions
7.1 Effect of Other Drugs on VERZENIO
(additions underlined)
CYP3A Inhibitors
Strong and moderate
CYP3A4 inhibitors increased the exposure of abemaciclib plus its active
metabolites to a clinically meaningful extent and may lead to increased
toxicity.
...
Other
Strong CYP3A Inhibitors
In patients with recommended
starting doses of 200 mg twice daily or 150 mg twice daily, reduce the VERZENIO
dose to 100 mg twice daily with concomitant use of strong CYP3A inhibitors other
than ketoconazole. In patients who have had a dose reduction to 100 mg
twice daily due to adverse reactions, further reduce the VERZENIO dose to 50 mg
twice daily
...
Moderate
CYP3A Inhibitors
With concomitant use of
moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing
the VERZENIO dose in 50 mg decrements as demonstrated in Table 1, if necessary.
Strong and Moderate CYP3A
Inducers
Coadministration of strong or
moderate CYP3A inducers decreased the plasma concentrations of
abemaciclib plus its active metabolites and may lead to reduced activity. Avoid
concomitant use of strong or moderate CYP3A inducers and consider
alternative agents.
8
Use in Specific Populations
8.5 Geriatric Use
(additions underlined)
Of the patients who received VERZENIO in MONARCH 1, MONARCH
2, and MONARCH 3, 38% were 65 years of age or older and 10% were 75
years of age or older. The most common adverse reactions (greater than
or equal to 5%) Grade 3 or 4 in patients greater than or equal to 65 years
of age across MONARCH 1, 2, and 3 were neutropenia, diarrhea, fatigue, nausea, dehydration,
leukopenia, anemia, infections, and ALT increased. No overall differences
in safety or effectiveness of VERZENIO were observed between these patients and
younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(additions
underlined)
…
Drug Interactions
Inform patients to avoid concomitant use of
ketoconazole. Dose reduction may be required for other strong CYP3A
inhibitors or for moderate CYP3A inhibitors.
Grapefruit may interact with VERZENIO. Advise
patients not to consume grapefruit products while on treatment with VERZENIO.
Advise patients to avoid concomitant use of strong
and moderate CYP3A inducers and to consider alternative agents.
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