6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Diarrhea [see Warnings and Precautions (5.1)].
Neutropenia [see Warnings and Precautions (5.2)].
Interstitial Lung Disease (ILD) or Pneumonitis [see Warnings and Precautions (5.3)].
Hepatotoxicity [see Warnings and Precautions (5.4)].
Venous Thromboembolism [see Warnings and Precautions (5.5)].

6.1 Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety population described in the Warnings and Precautions reflect exposure to VERZENIO in 3691 patients from four clinical trials: monarchE, MONARCH 1, MONARCH 2, and MONARCH 3. The safety population includes exposure to VERZENIO as a single agent at 200 mg twice daily in 132 patients in MONARCH 1 and to VERZENIO at 150 mg twice daily in 3559 patients administered in combination with fulvestrant, tamoxifen, or an aromatase inhibitor in monarchE, MONARCH 2, and MONARCH 3. The median duration of exposure ranged from 4.5 months in MONARCH 1 to 24 months in monarchE. The most common adverse reactions (incidence ≥20%) across clinical trials were: diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia.

Early Breast Cancer

monarchE: VERZENIO in Combination with Tamoxifen or an Aromatase Inhibitor as Adjuvant Treatment

Adult patients with HR-positive, HER2-negative, node-positive early breast cancer at a high risk of recurrence

The safety of VERZENIO was evaluated in monarchE, a study of 5591 adult patients receiving VERZENIO plus endocrine therapy (tamoxifen or an aromatase inhibitor) or endocrine therapy (tamoxifen or an aromatase inhibitor) alone [see Clinical Studies (14.1)]. Patients were randomly assigned to receive 150 mg of VERZENIO orally, twice daily, plus tamoxifen or an aromatase inhibitor, or tamoxifen or an aromatase inhibitor, for two years or until discontinuation criteria were met. The median duration of VERZENIO treatment was 24 months.

The most frequently reported (≥5%) Grade 3 or 4 adverse reactions were neutropenia, leukopenia, diarrhea, and lymphopenia.

Fatal adverse reactions occurred in 0.8% of patients who received VERZENIO plus endocrine therapy (tamoxifen or an aromatase inhibitor), including: cardiac failure (0.1%), cardiac arrest, myocardial infarction, ventricular fibrillation, cerebral hemorrhage, cerebrovascular accident, pneumonitis, hypoxia, diarrhea, and mesenteric artery thrombosis (0.03% each).

Permanent VERZENIO treatment discontinuation due to an adverse reaction was reported in 19% of patients receiving VERZENIO, plus tamoxifen or an aromatase inhibitor. Of the patients receiving tamoxifen or an aromatase inhibitor, 1% permanently discontinued due to an adverse reaction. The most common adverse reactions leading to VERZENIO discontinuations were diarrhea (5%), fatigue (2%), and neutropenia (0.9%).

Dose interruption of VERZENIO due to an adverse reaction occurred in 62% of patients receiving VERZENIO plus tamoxifen or aromatase inhibitors. Adverse reactions leading to VERZENIO dose interruptions in ≥5% of patients were diarrhea (20%), neutropenia (16%), leukopenia (7%), and fatigue (5%).

Dose reductions of VERZENIO due to an adverse reaction occurred in 44% of patients receiving VERZENIO plus endocrine therapy (tamoxifen or an aromatase inhibitor). Adverse reactions leading to VERZENIO dose reductions in ≥5% were diarrhea (17%), neutropenia (8%), and fatigue (5%).

The most common adverse reactions reported (≥20%) in the VERZENIO, plus tamoxifen or an aromatase inhibitor, arm and ≥2% higher than the tamoxifen or an aromatase inhibitor arm were: diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache. Adverse reactions are shown in Table 8 and laboratory abnormalities are shown in Table 9.

Table 8: Adverse Reactions (≥10%) of Patients Receiving VERZENIO Plus Tamoxifen or an Aromatase Inhibitor [with a Difference between Arms of ≥2%] in monarchE
a Includes the following fatal adverse reactions: diarrhea (n=1), and infections (n=4)
b Includes the following fatal adverse reactions: infections (n=5)
c Includes mouth ulceration, mucosal inflammation, oropharyngeal pain, stomatitis.
d Includes all reported preferred terms that are part of the Infections and Infestations system organ class. Most common infections (>5%) include upper respiratory tract infection, urinary tract infection, and nasopharyngitis.
e Includes asthenia, fatigue.
f Includes exfoliative rash, mucocutaneous rash, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculo-papular, rash maculovesicular, rash morbilliform, rash papular, rash papulosquamous, rash pruritic, rash vesicular, vulvovaginal rash.
	VERZENIO Plus Tamoxifen or an Aromatase Inhibitor N=2791			Tamoxifen or an Aromatase Inhibitor N=2800
	All Gradesa %	Grade 3 %	Grade 4 %	All Gradesb %	Grade 3 %	Grade 4 %
Gastrointestinal Disorders
Diarrhea	84	8	0	9	0.2	0
Nausea	30	0.5	0	9	<0.1	0
Vomiting	18	0.5	0	4.6	0.1	0
Stomatitisc	14	0.1	0	5	0	0
Infections and Infestations
Infectionsd	51	4.9	0.6	39	2.7	0.1
General Disorders and Administration Site Conditions
Fatiguee	41	2.9	0	18	0.1	0
Nervous System Disorders
Headache	20	0.3	0	15	0.2	0
Dizziness	11	0.1	0	7	<0.1	0
Metabolism and Nutrition Disorders
Decreased appetite	12	0.6	0	2.4	<0.1	0
Skin and Subcutaneous Tissue Disorders
Rashf	11	0.4	0	4.5	0	0
Alopecia	11	0	0	2.7	0	0

Clinically relevant adverse reactions in <10% of patients who received VERZENIO in combination with tamoxifen or an aromatase inhibitor in monarchE include:

Pruritus-9%
Dyspepsia-8%
Nail disorder-6% (includes nail bed disorder, nail bed inflammation, nail discoloration, nail disorder, nail dystrophy, nail pigmentation, nail ridging, nail toxicity, onychalgia, onychoclasis, onycholysis, onychomadesis)
Lacrimation increased-6%
Dysgeusia-5%
Interstitial lung disease (ILD)/pneumonitis-3% (includes pneumonitis, radiation pneumonitis, interstitial lung disease, pulmonary fibrosis, organizing pneumonia, radiation fibrosis – lung, lung opacity, sarcoidosis)
Venous thromboembolic events (VTEs)-3% (includes catheter site thrombosis, cerebral venous thrombosis, deep vein thrombosis, device related thrombosis, embolism, hepatic vein thrombosis, jugular vein occlusion, jugular vein thrombosis, ovarian vein thrombosis, portal vein thrombosis, pulmonary embolism, subclavian vein thrombosis, venous thrombosis limb)

Table 9: Laboratory Abnormalities (≥10%) in Patients Receiving VERZENIO Plus Tamoxifen or an Aromatase Inhibitor [with a Difference between Arms of ≥2%] in monarchE
	VERZENIO Plus Tamoxifen or an Aromatase Inhibitor N=2791			Tamoxifen or an Aromatase Inhibitor N=2800
	All Grades %	Grade 3 %	Grade 4 %	All Grades %	Grade 3 %	Grade 4 %
Creatinine increased	99	0.5	0	91	<0.1	0
White blood cell decreased	89	19	<0.1	28	1.1	0
Neutrophil count decreased	84	18	0.7	23	1.6	0.3
Anemia	68	1.0	0	17	0.1	0
Lymphocyte count decreased	59	13	0.2	24	2.4	0.1
Platelet count decreased	37	0.7	0.2	10	0.1	0.1
Alanine aminotransferase increased	37	2.5	<0.1	24	1.2	0
Aspartate aminotransferase increased	31	1.5	<0.1	18	0.9	0
Hypokalemia	11	1.2	0.1	3.8	0.1	0.1

Advanced or Metastatic Breast Cancer

MONARCH 3: VERZENIO in Combination with an Aromatase Inhibitor (Anastrozole or Letrozole) as Initial Endocrine-Based Therapy

Postmenopausal Women with HR-positive, HER2-negative locoregionally recurrent or metastatic breast cancer with no prior systemic therapy in this disease setting

The safety of VERZENIO was evaluated in MONARCH 3, a study of 488 women receiving VERZENIO plus an aromatase inhibitor or placebo plus an aromatase inhibitor [see Clinical Studies (14.2)]. Patients were randomly assigned to receive 150 mg of VERZENIO or placebo orally twice daily, plus physician's choice of anastrozole or letrozole once daily. Median duration of treatment was 15.1 months for the VERZENIO arm and 13.9 months for the placebo arm.

The most frequently reported (≥5%) Grade 3 or 4 adverse reactions were neutropenia, diarrhea, leukopenia, increased ALT, and anemia.

Deaths during treatment or during the 30-day follow up, regardless of causality, were reported in 11 cases (3%) of VERZENIO plus an aromatase inhibitor treated patients versus 3 cases (2%) of placebo plus an aromatase inhibitor treated patients. Causes of death for patients receiving VERZENIO plus an aromatase inhibitor included: 3 (0.9%) patient deaths due to underlying disease, 3 (0.9%) due to lung infection, 3 (0.9%) due to VTE, 1 (0.3%) due to pneumonitis, and 1 (0.3%) due to cerebral infarction.

Permanent treatment discontinuation due to an adverse reaction was reported in 13% of patients receiving VERZENIO plus an aromatase inhibitor and in 3% of patients receiving placebo plus an aromatase inhibitor. Adverse reactions leading to permanent discontinuation for patients receiving VERZENIO plus an aromatase inhibitor were diarrhea (2%), ALT increased (2%), infection (1%), venous thromboembolic events (VTE) (1%), neutropenia (0.9%), renal impairment (0.9%), AST increased (0.6%), dyspnea (0.6%), pulmonary fibrosis (0.6%) and anemia, rash, weight decreased and thrombocytopenia (each 0.3%).

Dose interruption of VERZENIO due to an adverse reaction occurred in 56% of patients receiving VERZENIO plus anastrozole or letrozole. Adverse reactions leading to VERZENIO dose interruptions in ≥5% of patients were neutropenia (16%) and diarrhea (15%).

Dose reductions due to an adverse reaction occurred in 43% of patients receiving VERZENIO plus anastrozole or letrozole. Adverse reactions leading to dose reductions in ≥5% of patients were diarrhea and neutropenia. VERZENIO dose reductions due to diarrhea of any grade occurred in 13% of patients receiving VERZENIO plus an aromatase inhibitor compared to 2% of patients receiving placebo plus an aromatase inhibitor. VERZENIO dose reductions due to neutropenia of any grade occurred in 11% of patients receiving VERZENIO plus an aromatase inhibitor compared to 0.6% of patients receiving placebo plus an aromatase inhibitor.

The most common adverse reactions reported (≥20%) in the VERZENIO arm and ≥2% than the placebo arm were: diarrhea, neutropenia, fatigue, infections, nausea, abdominal pain, anemia, vomiting, alopecia, decreased appetite, and leukopenia. Adverse reactions are shown in Table 10 and laboratory abnormalities in Table 11. Diarrhea incidence was greatest during the first month of VERZENIO dosing. The median time to onset of the first diarrhea event was 8 days, and the median durations of diarrhea for Grades 2 and for Grade 3 were 11 days and 8 days, respectively. Most diarrhea events recovered or resolved (88%) with supportive treatment and/or dose reductions [see Dosage and Administration (2.2) and Patient Counseling Information (17)]. Nineteen percent of patients with diarrhea required a dose omission and 13% required a dose reduction. The median time to the first dose reduction due to diarrhea was 38 days.

Table 10: Adverse Reactions (≥10%) in Patients Receiving VERZENIO Plus Anastrozole or Letrozole [with a Difference between Arms of ≥2%] in MONARCH 3
a Includes all reported preferred terms that are part of the Infections and Infestations system organ class. Most common infections (>1%) include upper respiratory tract infection, lung infection, and pharyngitis.
	VERZENIO plus Anastrozole or Letrozole N=327			Placebo plus Anastrozole or Letrozole N=161
	All Grades %	Grade 3 %	Grade 4 %	All Grades %	Grade 3 %	Grade 4 %
Gastrointestinal Disorders
Diarrhea	81	9	0	30	1.2	0
Nausea	39	0.9	0	20	1.2	0
Abdominal pain	29	1.2	0	12	1.2	0
Vomiting	28	1.2	0	12	1.9	0
Constipation	16	0.6	0	12	0	0
Infections and Infestations
Infectionsa	39	4.0	0.9	29	2.5	0.6
General Disorders and Administration Site Conditions
Fatigue	40	1.8	0	32	0	0
Influenza like illness	10	0	0	8	0	0
Skin and Subcutaneous Tissue Disorders
Alopecia	27	0	0	11	0	0
Rash	14	0.9	0	5	0	0
Pruritus	13	0	0	9	0	0
Metabolism and Nutrition Disorders
Decreased appetite	24	1.2	0	9	0.6	0
Investigations
Weight decreased	10	0.6	0	3.1	0.6	0
Respiratory, Thoracic, and Mediastinal Disorders
Cough	13	0	0	9	0	0
Dyspnea	12	0.6	0.3	6	0.6	0
Nervous System Disorders
Dizziness	11	0.3	0	9	0	0

Additional adverse reactions in MONARCH 3 include venous thromboembolic events (deep vein thrombosis, pulmonary embolism, and pelvic venous thrombosis), which were reported in 5% of patients treated with VERZENIO plus anastrozole or letrozole as compared to 0.6% of patients treated with anastrozole or letrozole plus placebo.

Table 11: Laboratory Abnormalities (≥10%) in Patients Receiving VERZENIO Plus Anastrozole or Letrozole [with a Difference Between Arms of ≥2%] in MONARCH 3
	VERZENIO plus Anastrozole or Letrozole N=327			Placebo plus Anastrozole or Letrozole N=161
Laboratory Abnormality	All Grades %	Grade 3 %	Grade 4 %	All Grades %	Grade 3 %	Grade 4 %
Creatinine increased	98	2.2	0	84	0	0
White blood cell decreased	82	13	0	27	0.6	0
Anemia	82	1.6	0	28	0	0
Neutrophil count decreased	80	19	2.9	21	2.6	0
Lymphocyte count decreased	53	7	0.6	26	1.9	0
Platelet count decreased	36	1.3	0.6	12	0.6	0
Alanine aminotransferase increased	48	6	0.6	25	1.9	0
Aspartate aminotransferase increased	37	3.8	0	23	0.6	0

Creatinine Increased

Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters, without affecting glomerular function [see Clinical Pharmacology (12.3)]. Across the clinical studies, increases in serum creatinine (mean increase, 0.2-0.3 mg/dL) occurred within the first 28-day cycle of VERZENIO dosing, remained elevated but stable through the treatment period, and were reversible upon treatment discontinuation. Alternative markers such as BUN, cystatin C, or calculated GFR, which are not based on creatinine, may be considered to determine whether renal function is impaired.

MONARCH 2: VERZENIO in Combination with Fulvestrant

Women with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression on or after prior adjuvant or metastatic endocrine therapy

The safety of VERZENIO (150 mg twice daily) plus fulvestrant (500 mg) versus placebo plus fulvestrant was evaluated in MONARCH 2 [see Clinical Studies (14.2)]. The data described below reflect exposure to VERZENIO in 441 patients with HR-positive, HER2-negative advanced breast cancer who received at least one dose of VERZENIO plus fulvestrant in MONARCH 2.

Median duration of treatment was 12 months for patients receiving VERZENIO plus fulvestrant and 8 months for patients receiving placebo plus fulvestrant.

The most frequently reported (≥5%) Grade 3 or 4 adverse reactions were neutropenia, diarrhea, leukopenia, anemia, and infections.

Deaths during treatment or during the 30-day follow up, regardless of causality, were reported in 18 cases (4%) of VERZENIO plus fulvestrant treated patients versus 10 cases (5%) of placebo plus fulvestrant treated patients. Causes of death for patients receiving VERZENIO plus fulvestrant included: 7 (2%) patient deaths due to underlying disease, 4 (0.9%) due to sepsis, 2 (0.5%) due to pneumonitis, 2 (0.5%) due to hepatotoxicity, and one (0.2%) due to cerebral infarction.

Permanent study treatment discontinuation due to an adverse reaction were reported in 9% of patients receiving VERZENIO plus fulvestrant and in 3% of patients receiving placebo plus fulvestrant. Adverse reactions leading to permanent discontinuation for patients receiving VERZENIO plus fulvestrant were infection (2%), diarrhea (1%), hepatotoxicity (1%), fatigue (0.7%), nausea (0.2%), abdominal pain (0.2%), acute kidney injury (0.2%), and cerebral infarction (0.2%).

Dose interruption of VERZENIO due to an adverse reaction occurred in 52% of patients receiving VERZENIO plus fulvestrant. Adverse reactions leading to VERZENIO dose interruptions in ≥5% of patients were diarrhea (19%) and neutropenia (16%).

Dose reductions due to an adverse reaction occurred in 43% of patients receiving VERZENIO plus fulvestrant. Adverse reactions leading to reductions in ≥5% of patients were diarrhea and neutropenia. VERZENIO dose reductions due to diarrhea of any grade occurred in 19% of patients receiving VERZENIO plus fulvestrant compared to 0.4% of patients receiving placebo and fulvestrant. VERZENIO dose reductions due to neutropenia of any grade occurred in 10% of patients receiving VERZENIO plus fulvestrant compared to no patients receiving placebo plus fulvestrant.

The most common adverse reactions reported (≥20%) in the VERZENIO arm were: diarrhea, fatigue, neutropenia, nausea, infections, abdominal pain, anemia, leukopenia, decreased appetite, vomiting, and headache. Adverse reactions are shown in Table 12 and laboratory abnormalities in Table 13.

Table 12: Adverse Reactions (≥10%) in Patients Receiving VERZENIO Plus Fulvestrant [with a Difference Between Arms of ≥2%] in MONARCH 2
a Includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, abdominal tenderness.
b Includes upper respiratory tract infection, urinary tract infection, lung infection, pharyngitis, conjunctivitis, sinusitis, vaginal infection, sepsis.
c Includes asthenia, fatigue.
	VERZENIO plus Fulvestrant N=441			Placebo plus Fulvestrant N=223
	All Grades %	Grade 3 %	Grade 4 %	All Grades %	Grade 3 %	Grade 4 %
Gastrointestinal Disorders
Diarrhea	86	13	0	25	0.4	0
Nausea	45	2.7	0	23	0.9	0
Abdominal paina	35	2.5	0	16	0.9	0
Vomiting	26	0.9	0	10	1.8	0
Stomatitis	15	0.5	0	10	0	0
Infections and Infestations
Infectionsb	43	5	0.7	25	3.1	0.4
General Disorders and Administration Site Conditions
Fatiguec	46	2.7	0	32	0.4	0
Edema peripheral	12	0	0	7	0	0
Pyrexia	11	0.5	0.2	6	0.4	0
Metabolism and Nutrition Disorders
Decreased appetite	27	1.1	0	12	0.4	0
Respiratory, Thoracic and Mediastinal Disorders
Cough	13	0	0	11	0	0
Skin and Subcutaneous Tissue Disorders
Alopecia	16	0	0	1.8	0	0
Pruritus	13	0	0	6	0	0
Rash	11	1.1	0	4.5	0	0
Nervous System Disorders
Headache	20	0.7	0	15	0.4	0
Dysgeusia	18	0	0	2.7	0	0
Dizziness	12	0.7	0	6	0	0
Investigations
Weight decreased	10	0.2	0	2.2	0.4	0

Additional adverse reactions in MONARCH 2 include venous thromboembolic events (deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, subclavian vein thrombosis, axillary vein thrombosis, and DVT inferior vena cava), which were reported in 5% of patients treated with VERZENIO plus fulvestrant as compared to 0.9% of patients treated with fulvestrant plus placebo.

Table 13: Laboratory Abnormalities (≥10%) in Patients Receiving VERZENIO Plus Fulvestrant [with a Difference Between Arms of ≥2%]in MONARCH 2
	VERZENIO plus Fulvestrant N=441			Placebo plus Fulvestrant N=223
	All Grades %	Grade 3 %	Grade 4 %	All Grades %	Grade 3 %	Grade 4 %
Creatinine increased	98	1.2	0	74	0	0
White blood cell decreased	90	23	0.7	33	0.9	0
Neutrophil count decreased	87	29	3.5	30	3.7	0.5
Anemia	84	2.6	0	34	0.5	0
Lymphocyte count decreased	63	12	0.2	32	1.8	0
Platelet count decreased	53	0.9	1.2	15	0	0
Alanine aminotransferase increased	41	3.9	0.7	32	1.4	0
Aspartate aminotransferase increased	37	3.9	0	25	3.7	0.5

Creatinine Increased

Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters, without affecting glomerular function [see Clinical Pharmacology (12.3)]. In clinical studies, increases in serum creatinine (mean increase, 0.2-0.3 mg/dL) occurred within the first 28-day cycle of VERZENIO dosing, remained elevated but stable through the treatment period, and were reversible upon treatment discontinuation. Alternative markers such as BUN, cystatin C, or calculated glomerular filtration rate (GFR), which are not based on creatinine, may be considered to determine whether renal function is impaired.

MONARCH 1: VERZENIO Administered as a Monotherapy in Metastatic Breast Cancer

Patients with HR-positive, HER2-negative breast cancer who received prior endocrine therapy and 1-2 chemotherapy regimens in the metastatic setting

The safety of VERZENIO was evaluated in MONARCH 1, a single-arm, open-label, multicenter study in 132 women with measurable HR-positive, HER2-negative metastatic breast cancer [see Clinical Studies (14.2)]. Patients received 200 mg VERZENIO orally twice daily until development of progressive disease or unmanageable toxicity. Median duration of treatment was 4.5 months.

The most frequently reported (≥5%) Grade 3 or 4 adverse reactions were diarrhea, neutropenia, fatigue, and leukopenia.

Deaths due to adverse reactions 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).

Ten patients (8%) discontinued study treatment from adverse reactions due to (1 patient each), abdominal pain, arterial thrombosis, aspartate aminotransferase (AST) increased, blood creatinine increased, chronic kidney disease, diarrhea, ECG QT prolonged, fatigue, hip fracture, and lymphopenia.

Dose interruption of VERZENIO due to an adverse reaction occurred in 58% of patients. The most frequent (≥5%) adverse reactions leading to dose interruptions were diarrhea (24%), neutropenia (16%), fatigue (10%), vomiting (6%), and nausea (5%).

Forty-nine percent of patients had dose reductions due to an adverse reaction. The most frequent adverse reactions that led to dose reductions were diarrhea (20%), neutropenia (11%), and fatigue (9%).

The most common reported adverse reactions (≥20%) were: diarrhea, fatigue, nausea, decreased appetite, abdominal pain, neutropenia, vomiting, infections, anemia, headache, and thrombocytopenia. Adverse reactions are shown in Table 14 and laboratory abnormalities in Table 15.

Table 14: Adverse Reactions (≥10%) of Patients in MONARCH 1
a Includes asthenia, fatigue.
	VERZENIO N=132
	All Grades %	Grade 3 %	Grade 4 %
Gastrointestinal Disorders
Diarrhea	90	20	0
Nausea	64	4.5	0
Abdominal pain	39	2.3	0
Vomiting	35	1.5	0
Constipation	17	0.8	0
Dry mouth	14	0	0
Stomatitis	14	0	0
Infections and Infestations
Infections	31	4.5	0
General Disorders and Administration Site Conditions
Fatiguea	65	13	0
Pyrexia	11	0	0
Metabolism and Nutrition Disorders
Decreased appetite	45	3.0	0
Dehydration	10	2.3	0
Respiratory, Thoracic and Mediastinal Disorders
Cough	19	0	0
Musculoskeletal and Connective Tissue Disorders
Arthralgia	15	0	0
Nervous System Disorders
Headache	20	0	0
Dysgeusia	12	0	0
Dizziness	11	0	0
Skin and Subcutaneous Tissue Disorders
Alopecia	12	0	0
Investigations
Weight decreased	14	0	0

Table 15: Laboratory Abnormalities for Patients Receiving VERZENIO in MONARCH 1
	VERZENIO N=132
	All Grades %	Grade 3 %	Grade 4 %
Creatinine increased	99	0.8	0
White blood cell decreased	91	28	0
Neutrophil count decreased	88	22	4.6
Anemia	69	0	0
Lymphocyte count decreased	42	13	0.8
Platelet count decreased	41	2.3	0
ALT increased	31	3.1	0
AST increased	30	3.8	0

Creatinine Increased

Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters, without affecting glomerular function [see Clinical Pharmacology (12.3)]. In clinical studies, increases in serum creatinine (mean increase, 0.2-0.3 mg/dL) occurred within the first 28-day cycle of VERZENIO dosing, remained elevated but stable through the treatment period, and were reversible upon treatment discontinuation. Alternative markers such as BUN, cystatin C, or calculated GFR, which are not based on creatinine, may be considered to determine whether renal function is impaired.

6.2 Postmarketing Experience

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 [see Warnings and Precautions (5.3)].

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