INDICATIONS
AND USAGE
VERZENIO® is a kinase inhibitor indicated:
DOSAGE AND
ADMINISTRATION
VERZENIO tablets are taken orally with or without food.
DOSAGE FORMS
AND STRENGTHS
Tablets: 50 mg, 100 mg, 150 mg, and 200 mg.
WARNINGS AND
PRECAUTIONS
ADVERSE
REACTIONS
Most common adverse reactions (incidence ≥20%) were diarrhea, neutropenia,
nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased
appetite, vomiting, headache, alopecia, and thrombocytopenia.
To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at
1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG
INTERACTIONS
USE IN SPECIFIC
POPULATIONS
Pregnancy
Risk Summary
Based on findings in animals and its mechanism of action, VERZENIO can cause
fetal harm when administered to a pregnant woman. There are no available human
data informing the drug-associated risk. Advise pregnant women of the potential
risk to a fetus. In animal reproduction studies, administration of abemaciclib
during organogenesis was teratogenic and caused decreased fetal weight at
maternal exposures that were similar to human clinical exposure based on AUC at
the maximum recommended human dose. Advise pregnant women of the potential risk
to a fetus.
The background risk of major birth defects and miscarriage for the indicated
population is unknown. However, the background risk in the U.S. general
population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of
clinically recognized pregnancies.
Data
Animal Data
In an embryo-fetal development study, pregnant rats received oral doses of
abemaciclib up to 15 mg/kg/day during the period of organogenesis. Doses
≥4 mg/kg/day caused decreased fetal body weights and increased incidence
of cardiovascular and skeletal malformations and variations. These findings
included absent innominate artery and aortic arch, malpositioned subclavian
artery, unossified sternebra, bipartite ossification of thoracic centrum, and
rudimentary or nodulated ribs. At 4 mg/kg/day in rats, the maternal
systemic exposures were approximately equal to the human exposure (AUC) at the
recommended dose.
Lactation
Risk Summary
There are no data on the presence of abemaciclib in human milk, or its effects
on the breastfed child or on milk production. Because of the potential for
serious adverse reactions in breastfed infants from VERZENIO, advise lactating
women not to breastfeed during VERZENIO treatment and for at least 3 weeks
after the last dose.
Females and Males of Reproductive Potential
Pregnancy Testing
Based on animal studies, VERZENIO can cause fetal harm when administered to a
pregnant woman. Pregnancy testing is recommended for females of reproductive
potential prior to initiating treatment with VERZENIO.
Contraception
Females
VERZENIO can cause fetal harm when administered to a pregnant woman. Advise
females of reproductive potential to use effective contraception during
VERZENIO treatment and for at least 3 weeks after the last dose.
Infertility
Males
Based on findings in animals, VERZENIO may impair fertility in males of
reproductive potential.
Pediatric Use
The safety and effectiveness of VERZENIO have not been established in pediatric
patients.
Geriatric Use
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. The
most common adverse reactions (≥5%) Grade 3 or 4 in patients ≥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.
Renal Impairment
No dosage adjustment is required for patients with mild or moderate renal
impairment (CLcr ≥30-89 mL/min, estimated by Cockcroft-Gault [C-G]). The
pharmacokinetics of abemaciclib in patients with severe renal impairment (CLcr
<30 mL/min, C-G), end stage renal disease, or in patients on dialysis
is unknown.
Hepatic Impairment
No dosage adjustments are necessary in patients with mild or moderate hepatic
impairment (Child-Pugh A or B).
Reduce the dosing frequency when administering VERZENIO to patients with severe
hepatic impairment (Child-Pugh C).
ICD CODES
Hr(+),
HEr2(-) advanced female breast
cancer |
|
C50 |
Malignant neoplasm of breast |
C50.1 |
Malignant neoplasm of central portion of breast |
C50.11 |
Malignant neoplasm of central portion of breast,
female |
C50.111 |
Malignant neoplasm of central portion of right
female breast |
C50.112 |
Malignant neoplasm of central portion of left
female breast |
C50.119 |
Malignant neoplasm of central portion of
unspecified female breast |
C50.2 |
Malignant neoplasm of upper-inner quadrant of
breast |
C50.21 |
Malignant neoplasm of upper-inner quadrant of
breast, female |
C50.211 |
Malignant neoplasm of upper-inner quadrant of right
female breast |
C50.212 |
Malignant neoplasm of upper-inner quadrant of left
female breast |
C50.219 |
Malignant neoplasm of upper-inner quadrant of
unspecified female breast |
C50.3 |
Malignant neoplasm of lower-inner quadrant of
breast |
C50.31 |
Malignant neoplasm of lower-inner quadrant of
breast, female |
C50.311 |
Malignant neoplasm of lower-inner quadrant of right
female breast |
C50.312 |
Malignant neoplasm of lower-inner quadrant of left
female breast |
C50.319 |
Malignant neoplasm of lower-inner quadrant of
unspecified female breast |
C50.4 |
Malignant neoplasm of upper-outer quadrant of
breast |
C50.41 |
Malignant neoplasm of upper-outer quadrant of
breast, female |
C50.411 |
Malignant neoplasm of upper-outer quadrant of right
female breast |
C50.412 |
Malignant neoplasm of upper-outer quadrant of left
female breast |
C50.419 |
Malignant neoplasm of upper-outer quadrant of
unspecified female breast |
C50.5 |
Malignant neoplasm of lower-outer quadrant of
breast |
C50.51 |
Malignant neoplasm of lower-outer quadrant of
breast, female |
C50.511 |
Malignant neoplasm of lower-outer quadrant of right
female breast |
C50.512 |
Malignant neoplasm of lower-outer quadrant of left
female breast |
C50.519 |
Malignant neoplasm of lower-outer quadrant of
unspecified female breast |
C50.6 |
Malignant neoplasm of axillary tail of breast |
C50.61 |
Malignant neoplasm of axillary tail of breast,
female |
C50.611 |
Malignant neoplasm of axillary tail of right female
breast |
C50.612 |
Malignant neoplasm of axillary tail of left female
breast |
C50.619 |
Malignant neoplasm of axillary tail of unspecified
female breast |
C50.8 |
Malignant neoplasm of overlapping sites of breast |
C50.81 |
Malignant neoplasm of overlapping sites of breast,
female |
C50.811 |
Malignant neoplasm of overlapping sites of right
female breast |
C50.812 |
Malignant neoplasm of overlapping sites of left
female breast |
C50.819 |
Malignant neoplasm of overlapping sites of
unspecified female breast |
C50.9 |
Malignant neoplasm of breast of unspecified site |
C50.91 |
Malignant neoplasm of breast of unspecified site,
female |
C50.911 |
Malignant neoplasm of unspecified site of right
female breast |
C50.912 |
Malignant neoplasm of unspecified site of left
female breast |
C50.919 |
Malignant neoplasm of unspecified site of
unspecified female breast |
Z17.0 |
Estrogen receptor positive status [Er+] |
Z19.1 |
Hormone sensitive malignancy status |
This site is
intended for US healthcare providers only.
PP-AL-US-2508 11/2020 © Lilly USA, LLC
2020. All rights reserved.
Verzenio® is a registered trademark and Verzenio Continuous
Care™ is a trademark owned or licensed by Eli Lilly and
Company, its subsidiaries or affiliates.
Please see
full Prescribing
Information for Verzenio.
Indication
& Important Safety Information
Indication
Verzenio is indicated for the treatment of hormone receptor–positive (HR+),
human epidermal growth factor receptor 2-negative (HER2-) advanced or
metastatic breast cancer (MBC)1:
Important Safety Information
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.
Instruct patients that at the first sign of loose stools, they should start
antidiarrheal therapy such as loperamide, increase oral fluids, and notify
their healthcare provider for further instructions and appropriate follow-up.
For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization,
discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume
Verzenio at the next lower dose.
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 ≥3 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 alone in MONARCH 1. In MONARCH 3, the
median time to first episode of Grade ≥3 neutropenia was 33 days, and in
MONARCH 2 and MONARCH 1, was 29 days. In MONARCH 3, median duration of Grade ≥3
neutropenia was 11 days, and for MONARCH 2 and MONARCH 1 was 15 days.
Monitor complete blood counts 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, or delay in starting treatment
cycles is recommended for patients who develop Grade 3 or 4 neutropenia.
Febrile neutropenia has been reported in <1% of patients exposed to Verzenio
in the MONARCH studies. Two deaths due to neutropenic sepsis were observed in
MONARCH 2. Inform patients to promptly report any episodes of fever to their
healthcare provider.
Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or
pneumonitis can occur in patients treated with Verzenio and other
CDK4/6 inhibitors. Across clinical trials (MONARCH 1, MONARCH 2, 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 post-marketing 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 in patients who develop
persistent or recurrent Grade 2 ILD/pneumonitis. Permanently discontinue
Verzenio in all patients with grade 3 or 4 ILD/pneumonitis.
Grade ≥3 increases in alanine aminotransferase (ALT) (6%
versus 2%) and aspartate aminotransferase (AST) (3% versus 1%)
were reported in the Verzenio and placebo arms, respectively, in MONARCH 3.
Grade ≥3 increases in ALT (4% versus 2%) and AST (2% versus 3%) were reported
in the Verzenio and placebo arms respectively, in MONARCH 2.
In MONARCH 3, for patients receiving Verzenio plus an aromatase inhibitor with
Grade ≥3 increases in ALT or AST, median time to onset was 61 and 71 days,
respectively, and median time to resolution to Grade <3 was 14 and 15 days,
respectively. In MONARCH 2, for patients receiving Verzenio plus fulvestrant
with Grade ≥3 increases in ALT or AST, median time to onset was 57 and 185
days, respectively, and median time to resolution to Grade <3 was 14 and 13
days, respectively.
For assessment of potential hepatotoxicity, 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 Grade 3 or 4, hepatic transaminase elevation.
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 3. Venous
thromboembolic events were reported in 5% of patients treated with Verzenio
plus fulvestrant in MONARCH 2 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. Monitor patients for signs and symptoms of
venous thrombosis and pulmonary embolism and treat as medically appropriate.
Verzenio can cause fetal harm when administered to a pregnant
woman based on findings from animal studies and the mechanism of action. In
animal reproduction studies, administration of abemaciclib to pregnant rats
during the period of organogenesis caused teratogenicity and decreased fetal
weight at maternal exposures that were similar to the human clinical exposure
based on area under the curve (AUC) at the maximum recommended human dose.
Advise pregnant women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during treatment with
Verzenio and for at least 3 weeks after the last dose. There are no data on the
presence of Verzenio in human milk or its effects on the breastfed child or on
milk production. Advise lactating women not to breastfeed during Verzenio
treatment and for at least 3 weeks after the last dose because of the potential
for serious adverse reactions in breastfed infants. Based on findings in
animals, Verzenio may impair fertility in males of reproductive potential.
The most common adverse reactions (all grades, ≥10%) observed
in MONARCH 3 for Verzenio plus anastrozole or letrozole and ≥2%
higher than placebo plus anastrozole or letrozole vs placebo plus anastrozole
or letrozole were diarrhea (81% vs 30%), neutropenia (41% vs 2%),
fatigue (40% vs 32%), infections (39% vs 29%), nausea (39% vs 20%), abdominal
pain (29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia (27% vs
11%), decreased appetite (24% vs 9%), leukopenia (21% vs 2%), creatinine
increased (19% vs 4%), constipation (16% vs 12%), ALT increased (16% vs 7%),
AST increased (15% vs 7%), rash (14% vs 5%), pruritus (13% vs 9%), cough (13%
vs 9%), dyspnea (12% vs 6%), dizziness (11% vs 9%), weight decreased (10% vs
3%), influenza-like illness (10% vs 8%), and thrombocytopenia (10% vs 2%).
The most common adverse reactions (all grades, ≥10%) observed
in MONARCH 2 for Verzenio plus fulvestrant and ≥2% higher than placebo
plus fulvestrant vs placebo plus fulvestrant were diarrhea (86% vs
25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%),
infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%),
leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%),
headache (20% vs 15%), dysgeusia (18% vs 3%), thrombocytopenia (16% vs 3%),
alopecia (16% vs 2%), stomatitis (15% vs 10%), ALT increased (13% vs 5%),
pruritus (13% vs 6%), cough (13% vs 11%), dizziness (12% vs 6%), AST increased
(12% vs 7%), peripheral edema (12% vs 7%), creatinine increased (12% vs
<1%), rash (11% vs 4%), pyrexia (11% vs 6%), and weight decreased (10% vs
2%).
The most common adverse reactions (all grades, ≥10%) observed
in MONARCH 1 with Verzenio were diarrhea (90%), fatigue (65%),
nausea (64%), decreased appetite (45%), abdominal pain (39%), neutropenia
(37%), vomiting (35%), infections (31%), anemia (25%), thrombocytopenia (20%),
headache (20%), cough (19%), leukopenia (17%), constipation (17%), arthralgia
(15%), dry mouth (14%), weight decreased (14%), stomatitis (14%), creatinine
increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%), dizziness
(11%), and dehydration (10%).
The most frequently reported ≥5% Grade 3 or 4 adverse reactions that
occurred in the Verzenio arm vs the placebo arm of MONARCH 3 were
neutropenia (22% vs 2%), diarrhea (9% vs 1%), leukopenia (8% vs <1%), ALT
increased (7% vs 2%), and anemia (6% vs 1%).
The most frequently reported ≥5% Grade 3 or 4 adverse reactions that
occurred in the Verzenio arm vs the placebo arm of MONARCH 2 were
neutropenia (27% vs 2%), diarrhea (13% vs <1%), leukopenia (9% vs 0%),
anemia (7% vs 1%), and infections (6% vs 3%).
The most frequently reported ≥5% Grade 3 or 4 adverse reactions from MONARCH
1 with Verzenio were neutropenia (24%), diarrhea (20%), fatigue (13%),
infections (7%), leukopenia (6%), anemia (5%), and nausea (5%).
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3
in ≥10% for Verzenio plus anastrozole or letrozole and ≥2% higher than placebo
plus anastrozole or letrozole vs placebo plus anastrozole or letrozole were
increased serum creatinine (98% vs 84%; 2% vs 0%), decreased white blood cells
(82% vs 27%; 13% vs <1%), anemia (82% vs 28%; 2% vs 0%), decreased
neutrophil count (80% vs 21%; 22% vs 3%), decreased lymphocyte count (53% vs
26%; 8% vs 2%), decreased platelet count (36% vs 12%; 2% vs <1%), increased
ALT (48% vs 25%; 7% vs 2%), and increased AST (37% vs 23%; 4% vs <1%).
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2
in ≥10% for Verzenio plus fulvestrant and ≥2% higher than placebo plus
fulvestrant vs placebo plus fulvestrant were increased serum
creatinine (98% vs 74%; 1% vs 0%), decreased white blood cells (90% vs 33%; 23%
vs 1%), decreased neutrophil count (87% vs 30%; 33% vs 4%), anemia (84% vs 33%;
3% vs <1%), decreased lymphocyte count (63% vs 32%; 12% vs 2%), decreased
platelet count (53% vs 15%; 2% vs 0%), increased ALT (41% vs 32%; 5% vs 1%),
and increased AST (37% vs 25%; 4% vs 4%).
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 with
Verzenio were increased serum creatinine (98%; <1%), decreased white blood
cells (91%; 28%), decreased neutrophil count (88%; 27%), anemia (68%; 0%),
decreased lymphocyte count (42%; 14%), decreased platelet count (41%; 2%),
increased ALT (31%; 3%), and increased AST (30%; 4%).
Strong and moderate CYP3A inhibitors increased the exposure of
abemaciclib plus its active metabolites to a clinically meaningful extent and
may lead to increased toxicity. Avoid concomitant use of the strong CYP3A
inhibitor ketoconazole. Ketoconazole is predicted to increase the AUC of
abemaciclib by up to 16-fold. 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
with concomitant use of strong CYP3A inhibitors. If a patient taking Verzenio
discontinues a strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5
half-lives of the inhibitor) to the dose that was used before starting the
inhibitor. With concomitant use of moderate CYP3A inhibitors, monitor for
adverse reactions and consider reducing the Verzenio dose in 50 mg decrements.
Patients should avoid grapefruit products.
Avoid concomitant use of strong or moderate CYP3A inducers and consider
alternative agents. Coadministration of strong or moderate CYP3A
inducers decreased the plasma concentrations of abemaciclib plus its active
metabolites and may lead to reduced activity.
With severe hepatic impairment (Child-Pugh Class C), reduce the
Verzenio dosing frequency to once daily. The pharmacokinetics of Verzenio in
patients with severe renal impairment (CLcr <30 mL/min),
end stage renal disease, or in patients on dialysis is unknown. No
dosage adjustments are necessary in patients with mild or moderate hepatic
(Child-Pugh A or B) and/or renal impairment (CLcr ≥30-89 mL/min).
Please see full Prescribing Information for Verzenio.
AL HCP ISI 17SEP2019
Reference: 1. Verzenio [package insert]. Indianapolis, IN: Eli
Lilly and Company; 2020.