VERZENIO ® (abemaciclib) is indicated: in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence. VERZENIO (abemaciclib) is indicated: in combination with an aromatase inhibitor as initial endocrine-based ...
VERZENIO in Combination with Imlunestrant Select patients for treatment of ER-positive, HER2-negative advanced or metastatic breast cancer with VERZENIO in combination with imlunestrant based on the presence of ESR1 mutation(s) in a plasma specimen using an FDA authorized test [see Indications and Usage ( 1.2 ) and Clinical Studies ( 14.2 )] . Information on FDA-authorized tests for the detection of ESR1 mutations...
How Supplied Strength Description Blister Pack Configuration NDC 200 mg Oval beige tablet with "Lilly" debossed on one side and "200" on the other side Blister pack containing 14 tablets (7-day supply) 0002-6216-54 150 mg Oval yellow tablet with "Lilly" debossed on one side and "150" on the other side Blister pack containing 14 tablets (7-day supply) 0002-5337-54 100 mg Oval white to practically white tablet with ...
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www.verzenio.comVERZENIO® (abemaciclib) is indicated:
VERZENIO (abemaciclib) is indicated:
VERZENIO in Combination with Imlunestrant
Select patients for treatment of ER-positive, HER2-negative advanced or metastatic breast cancer with VERZENIO in combination with imlunestrant based on the presence of ESR1 mutation(s) in a plasma specimen using an FDA authorized test [see Indications and Usage (1.2) and Clinical Studies (14.2)].
Information on FDA-authorized tests for the detection of ESR1 mutations in breast cancer is available at: www.fda.gov/CompanionDiagnostics.
VERZENIO in Combination with Fulvestrant, Tamoxifen, Imlunestrant or An Aromatase Inhibitor
The recommended dosage of VERZENIO is 150 mg orally twice daily.
For premenopausal and perimenopausal women and men treated with VERZENIO in combination with an aromatase inhibitor, imlunestrant, or fulvestrant should be treated with a gonadotropin-releasing hormone agonist (GnRH) according to current clinical practice standards.
Refer to the Prescribing Information for the recommended dose of the fulvestrant, tamoxifen, imlunestrant or aromatase inhibitor being used.
VERZENIO Monotherapy
The recommended dosage of VERZENIO as monotherapy is 200 mg orally twice daily.
Administration
Take VERZENIO orally, with or without food, at approximately the same times every day [see Clinical Pharmacology (12.3)].
Swallow VERZENIO tablets whole. Do not chew, crush, or split tablets. Do not ingest VERZENIO tablets if broken, cracked, or otherwise not intact.
Missed Dose
If a dose of VERZENIO is missed, skip the missed dose and take the next dose at the next scheduled time.
Vomited Dose
If vomiting occurs after taking a dose of VERZENIO, do not take an additional dose. Take the next dose at the next scheduled time.
The recommended VERZENIO dose reductions for adverse reactions are provided in Table 1. Permanently discontinue VERZENIO for patients unable to tolerate 50 mg twice daily.
| Dosage Level | VERZENIO Dose in Combination with Fulvestrant, Tamoxifen, Imlunestrant or an Aromatase Inhibitor | VERZENIO Dose for Monotherapy |
| Recommended starting dosage | 150 mg twice daily | 200 mg twice daily |
| First dosage reduction | 100 mg twice daily | 150 mg twice daily |
| Second dosage reduction | 50 mg twice daily | 100 mg twice daily |
| Third dosage reduction | not applicable | 50 mg twice daily |
The recommended VERZENIO dosage modifications for adverse reactions are provided in Tables 2-7.
| |
| |
| 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. | |
| CTCAE Grade | VERZENIO Dosage Modifications |
| Grade 1 or 2 | No dosage modification is required. |
| Grade 3 | Withhold until toxicity resolves to ≤Grade 2. Dosage reduction is not required. |
| Grade 3 recurrent, or Grade 4 | Withhold until toxicity resolves to ≤Grade 2. Resume at next lower dose. |
| At the first sign of loose stools, start treatment with antidiarrheal agents and increase intake of oral fluids. | |
| CTCAE Grade | VERZENIO Dosage Modifications |
| Grade 1 | No dosage modification is required. |
| Grade 2 | If toxicity does not resolve within 24 hours to ≤Grade 1, Withhold until resolution. No dosage reduction is required. |
| Grade 2 that persists or recurs after resuming the same dose despite maximal supportive measures | Withhold until toxicity resolves to ≤Grade 1. Resume at next lower dose. |
| Grade 3 or 4 or requires hospitalization | Withhold until toxicity resolves to ≤Grade 1. Resume at next lower dose. |
| |
| Monitor ALT, AST, and serum bilirubin 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. | |
| CTCAE Grade for ALT and AST | VERZENIO Dosage Modifications |
| Grade 1 (>ULN-3.0 x ULN) Grade 2 (>3.0-5.0 x ULN), WITHOUT increase in total bilirubin above 2 x ULN | No dosage modification is required. |
| Persistent or Recurrent Grade 2, or Grade 3 (>5.0-20.0 x ULN), WITHOUT increase in total bilirubin above 2 x ULN | Withhold until toxicity resolves to baseline or Grade 1. Resume at next lower dose. |
| Elevation in AST and/or ALT >3 x ULN WITH total bilirubin >2 x ULN, in the absence of cholestasis | Discontinue VERZENIO. |
| Grade 4 (>20.0 x ULN) | Discontinue VERZENIO. |
| CTCAE Grade | VERZENIO Dosage Modifications |
| Grade 1 or 2 | No dosage modification is required. |
| Persistent or recurrent Grade 2 toxicity that does not resolve with maximal supportive measures within 7 days to baseline or Grade 1 | Withhold until toxicity resolves to baseline or ≤Grade 1. Resume at next lower dose. |
| Grade 3 or 4 | Discontinue VERZENIO. |
| CTCAE Grade | VERZENIO Dosage Modifications |
| Early Breast Cancer | |
| Any Grade | Withhold and treat as clinically indicated. Resume VERZENIO when the patient is clinically stable. |
| Advanced or Metastatic Breast Cancer | |
| Grade 1 or 2 | No dosage modification is required. |
| Grade 3 or 4 | Withhold and treat as clinically indicated. Resume VERZENIO when the patient is clinically stable. |
| |
| CTCAE Grade | VERZENIO Dosage Modifications |
| Grade 1 or 2 | No dosage modification is required. |
| Persistent or recurrent Grade 2 toxicity that does not resolve with maximal supportive measures within 7 days to baseline or Grade 1 | Withhold until toxicity resolves to baseline or ≤Grade 1. Resume at next lower dose. |
| Grade 3 or 4 | Withhold until toxicity resolves to baseline or ≤Grade 1. Resume at next lower dose. |
Refer to the Prescribing Information for coadministered fulvestrant, tamoxifen, imlunestrant or an aromatase inhibitor for dose modifications and other relevant safety information.
Avoid concomitant use of the strong CYP3A inhibitor ketoconazole.
With concomitant use of strong CYP3A inhibitors other than ketoconazole, in patients with recommended starting dosage of 200 mg twice daily or 150 mg twice daily, reduce the VERZENIO dosage to 100 mg twice daily. In patients who have had a dosage reduction to 100 mg twice daily due to adverse reactions, further reduce the VERZENIO dosage to 50 mg twice daily. If a patient taking VERZENIO discontinues a CYP3A inhibitor, increase the VERZENIO dosage (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the strong inhibitor [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
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.
For patients with severe hepatic impairment (Child Pugh-C), reduce the VERZENIO dosage frequency to once daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Refer to the Full Prescribing Information for the coadministered fulvestrant, tamoxifen, imlunestrant or aromatase inhibitor for dose modification requirements for severe hepatic impairment.
50 mg tablets: oval beige tablet with “Lilly” debossed on one side and “50” on the other side.
100 mg tablets: oval white to practically white tablet with “Lilly” debossed on one side and “100” on the other side.
150 mg tablets: oval yellow tablet with “Lilly” debossed on one side and “150” on the other side.
200 mg tablets: oval beige tablet with “Lilly” debossed on one side and “200” on the other side.
None.
Severe diarrhea associated with dehydration and infection occurred in patients treated with VERZENIO.
Across five clinical trials in 3899 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, withhold VERZENIO until resolution to ≤Grade 1, and then resume VERZENIO at the next lower dose [see Dosage and Administration (2.2)].
Neutropenia, including febrile neutropenia and fatal neutropenic sepsis, occurred in patients treated with VERZENIO.
Across five clinical trials in 3899 patients, neutropenia occurred in 37% to 51% of patients receiving VERZENIO. A Grade ≥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 ≥3 neutropenia ranged from 29 days to 34 days, and the median duration of Grade ≥3 neutropenia ranged from 10 days to 16 days [see Adverse Reactions (6.1)].
Febrile neutropenia has been reported in <1% of patients receiving 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)].
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 [see Dosage and Administration (2.2)].
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=1108) (MONARCH 1, MONARCH 2, MONARCH 3, EMBER-3), 3.2% of VERZENIO-treated patients had ILD or pneumonitis of any grade: 0.5% had Grade 3 or 4, and 0.5% had fatal outcomes. Additional cases of ILD or pneumonitis have been observed in the postmarketing setting, with fatalities reported [see Adverse Reactions (6.2)].
Monitor patients for pulmonary symptoms indicative of ILD or 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.
Withhold or reduce dose for patients who develop persistent or recurrent Grade 2 ILD or pneumonitis. Permanently discontinue VERZENIO in all patients with Grade 3 or 4 ILD or pneumonitis [see Dosage and Administration (2.2)].
Grade ≥3 ALT (2% to 6%) and AST (2% to 3%) were reported in patients receiving VERZENIO.
Across four clinical trials in 3767 patients (monarchE, MONARCH 2, MONARCH 3, EMBER-3), the median time to onset of Grade ≥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 ≥3 AST increases ranged from 71 to 185 days and the median time to resolution to Grade <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 (2.2)].
Across four clinical trials in 3767 patients (monarchE, MONARCH 2, MONARCH 3, EMBER-3), venous thromboembolic (VTE) events occurred in 2% to 5% of patients treated with VERZENIO. VTE events included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, inferior vena cava thrombosis, jugular vein thrombosis, peripheral vein thrombosis and superficial vein thrombosis. In clinical trials, deaths due to VTE occurred in patients treated with VERZENIO.
VERZENIO has not been studied in patients with early breast cancer who had a history of VTE. 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 VTE event and for advanced or metastatic breast cancer patients with a Grade 3 or 4 VTE event [see Dosage and Administration (2.2)].
Based on findings from animal studies and the mechanism of action, VERZENIO can cause fetal harm when administered to a pregnant woman. 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 3 weeks after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
VERZENIO can increase serum creatinine. Across five clinical trials in 3899 patients (monarchE, MONARCH 1, MONARCH 2, MONARCH 3, and EMBER-3), increases in serum creatinine (mean increase, 0.2-0.3 mg/dL) occurred within the first 28-day cycle of VERZENIO treatment, remained elevated through the treatment, and were reversible upon treatment discontinuation. These increases were not associated with changes in glomerular function [see Adverse Reactions (6.1)]. The increases in serum creatinine may be due to inhibition of renal tubular secretion transporters [see Clinical Pharmacology (12.3)]. During VERZENIO treatment, use alternative measures that are not based on serum creatinine to assess renal function such as BUN, cystatin C, or calculated GFR.
The following adverse reactions are discussed in greater detail in other sections of the labeling:
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 3899 patients from five clinical trials including 132 patients treated with VERZENIO as monotherapy at 200 mg twice daily in MONARCH 1, 3767 patients treated with VERZENIO in combination with fulvestrant, tamoxifen, imlunestrant or an aromatase inhibitor at 150 mg twice daily in MONARCH 2, monarchE, EMBER-3, 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, infections, neutropenia, fatigue, abdominal pain, nausea, leukopenia, anemia, and vomiting.
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 in combination with 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, in combination with 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 (range: 1-28 months).
Serious adverse reactions occurred in 15% of patients who received VERZENIO in combination with endocrine therapy (tamoxifen or an aromatase inhibitor). Serious adverse reactions in ≥1% of patients included venous thromboembolism (VTE) (1.2%) and pneumonia (1%). 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 discontinuation of VERZENIO due to an adverse reaction occurred in 19% of patients. Adverse reactions which resulted in permanent discontinuation in >1% of patients were diarrhea (5%), and fatigue (2%).
Dosage interruptions of VERZENIO due to an adverse reaction occurred in 62% of patients. Adverse reactions which required dosage 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. Adverse reactions which required dose reductions in ≥5% of patients were diarrhea (17%), neutropenia (8%), and fatigue (5%).
The most common (>20%) adverse reactions, including laboratory abnormalities in the VERZENIO plus tamoxifen or an aromatase inhibitor arm and ≥2% higher than the tamoxifen or an aromatase inhibitor arm were: increased creatinine, decreased neutrophils, diarrhea, decreased hemoglobin, decreased lymphocytes, infections, fatigue, increased alanine aminotransferase (ALT), decreased platelets, increased aspartate aminotransferase (AST), nausea, and headache.
Adverse reactions are shown in Table 8 and laboratory abnormalities are shown in Table 9.
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Adverse Reactiona | 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 % | |
| 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 |
| Stomatitisb | 14 | 0.1 | 0 | 5 | 0 | 0 |
| Infections and Infestations | ||||||
| Infectionsb | 51 | 4.9 | 0.6 | 39 | 2.7 | 0.1 |
| General Disorders and Administration Site Conditions | ||||||
| Fatigueb | 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 | ||||||
| Rashb | 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%), increased lacrimation (6%), dysgeusia (5%), ILD/pneumonitis (3%), and VTE (3%).
| 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 % | |
| Chemistry | ||||||
| Creatinine increased | 99 | 0.5 | 0 | 91 | <0.1 | 0 |
| ALT increased | 37 | 2.5 | <0.1 | 24 | 1.2 | 0 |
| AST increased | 31 | 1.5 | <0.1 | 18 | 0.9 | 0 |
| Potassium decreased | 11 | 1.2 | 0.1 | 3.8 | 0.1 | 0.1 |
| Hematology | ||||||
| Neutrophils decreased | 84 | 18 | 0.7 | 23 | 1.6 | 0.3 |
| Hemoglobin decreased | 68 | 1 | 0 | 17 | 0.1 | 0 |
| Lymphocytes decreased | 59 | 13 | 0.2 | 24 | 2.4 | 0.1 |
| Platelets decreased | 37 | 0.7 | 0.2 | 10 | 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 in combination with an aromatase inhibitor or placebo in combination with an aromatase inhibitor [see Clinical Studies (14.2)]. Patients were randomly assigned to receive 150 mg of VERZENIO or placebo orally twice daily, in combination with investigator's choice of anastrozole or letrozole once daily until discontinuation criteria were met. The median duration of VERZENIO treatment was 15.1 months (range: 5 days – 27.4 months).
Serious adverse reactions occurred in 28% of patients who received VERZENIO plus an aromatase inhibitor. Serious adverse reactions in ≥1.5% of patients included infections (6%), VTE (2.5%) and diarrhea and anemia (1.5%, each). Fatal adverse reactions occurred in 3% of patients who received VERZENIO including underlying disease (0.9%), lung infection (0.9%), VTE (0.9%), pneumonitis (0.3%), and cerebral infarction (0.3%).
Permanent discontinuation of VERZENIO due to an adverse reaction occurred in 13% of patients. Adverse reactions which resulted in permanent discontinuation in >1% of patients were diarrhea (2%), ALT increased (2%), infection (1%), and VTE (1%).
Dosage interruptions of VERZENIO due to an adverse reaction occurred in 56% of patients. Adverse reactions which required dosage interruptions in ≥5% of patients were neutropenia (16%) and diarrhea (15%).
Dose reductions of VERZENIO due to an adverse reaction occurred in 43% of patients. Adverse reactions which required dose reductions in ≥5% of patients were diarrhea (13%) and neutropenia (11%).
The most common (≥20%) adverse reactions including laboratory abnormalities in the VERZENIO plus aromatase inhibitor arm and ≥2% higher than the placebo arm were: increased creatinine, decreased hemoglobin, diarrhea, decreased neutrophils, decreased lymphocytes, increased ALT, fatigue, infections, nausea, increased AST, decreased platelets, abdominal pain, anemia, vomiting, alopecia, and decreased appetite.
Adverse reactions are shown in Table 10 and laboratory abnormalities in Table 11.
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| Adverse Reactiona | 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 | ||||||
| Infectionsb | 39 | 4 | 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 |
| 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 |
| Investigations | ||||||
| Decreased weight | 10 | 0.6 | 0 | 3.1 | 0.6 | 0 |
Clinically relevant adverse reactions (<10%) in patients who received VERZENIO in combination with an aromatase inhibitor included: VTE (5%).
| 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 % |
| Chemistry | ||||||
| Creatinine increased | 98 | 2.2 | 0 | 84 | 0 | 0 |
| ALT increased | 48 | 6 | 0.6 | 25 | 1.9 | 0 |
| AST increased | 37 | 3.8 | 0 | 23 | 0.6 | 0 |
| Hematology | ||||||
| Hemoglobin decreased | 82 | 1.6 | 0 | 28 | 0 | 0 |
| Neutrophils decreased | 80 | 19 | 2.9 | 21 | 2.6 | 0 |
| Lymphocytes decreased | 53 | 7 | 0.6 | 26 | 1.9 | 0 |
| Platelets decreased | 36 | 1.3 | 0.6 | 12 | 0.6 | 0 |
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 in combination with fulvestrant versus placebo was evaluated in 664 patients with HR-positive, HER2-negative advanced breast cancer in MONARCH 2 [see Clinical Studies (14.2)]. Patients were randomized (2:1) to receive VERZENIO 150 mg orally twice daily in combination with fulvestrant (N=441) or placebo in combination with fulvestrant (N=223). Among patients treated with VERZENIO plus fulvestrant, the median duration of exposure was 12 months (range: 1 day – 27.8 months).
Serious adverse reactions occurred in 22% of patients who received VERZENIO in combination with fulvestrant. Serious adverse reactions in >1% of patients included VTE and pneumonia (1.8%, each), diarrhea (1.6%), cough (1.4%), sepsis (1.4%) and nausea and acute kidney injury (1.1% each). Fatal adverse reactions occurred in 4% of patients who received VERZENIO plus fulvestrant including underlying disease (2%), sepsis (0.9%), pneumonitis and hepatotoxicity (0.5% each), and cerebral infarction (0.2%).
Permanent discontinuation of VERZENIO due to an adverse reaction occurred in 9% of patients. Adverse reactions which resulted in permanent discontinuation in >1% of patients were infection (2%), and diarrhea and hepatotoxicity (1%, each).
Dosage interruptions of VERZENIO due to an adverse reaction occurred in 52% of patients. Adverse reactions which required dosage interruptions in ≥5% of patients were diarrhea (19%) and neutropenia (16%).
Dose reductions of VERZENIO due to an adverse reaction occurred in 43% of patients. Adverse reactions which required dose reductions in ≥5% of patients were diarrhea (19%) and neutropenia (10%).
The most common (≥20%) adverse reactions, including laboratory abnormalities, in the VERZENIO plus fulvestrant arm and with a ≥ 2% higher than the placebo plus fulvestrant arm were: increased creatinine, decreased neutrophils, diarrhea, decreased hemoglobin, decreased platelets, fatigue, nausea, infections, increased ALT, increased AST, abdominal pain, decreased appetite, vomiting, and headache.
Adverse reactions are shown in Table 12 and laboratory abnormalities in Table 13.
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Adverse Reactiona | 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 painb | 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 |
| General Disorders and Administration Site Conditions | ||||||
| Fatigueb | 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 |
| Infections and Infestations | ||||||
| Infectionsb | 43 | 5 | 0.7 | 25 | 3.1 | 0.4 |
| Metabolism and Nutrition Disorders | ||||||
| Decreased appetite | 27 | 1.1 | 0 | 12 | 0.4 | 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 |
| 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 |
| Respiratory, Thoracic and Mediastinal Disorders | ||||||
| Cough | 13 | 0 | 0 | 11 | 0 | 0 |
| Investigations | ||||||
| Weight decreased | 10 | 0.2 | 0 | 2.2 | 0.4 | 0 |
Clinically relevant adverse reactions (<10%) in patients who received VERZENIO in combination with fulvestrant included:
VTE (5%)
| VERZENIO plus Fulvestrant N=441 | Placebo plus Fulvestrant N=223 | |||||
| All Grades % | Grade 3 % | Grade 4 % | All Grades % | Grade 3 % | Grade 4 % | |
| Chemistry | ||||||
| Creatinine increased | 98 | 1.2 | 0 | 74 | 0 | 0 |
| ALT increased | 41 | 3.9 | 0.7 | 32 | 1.4 | 0 |
| AST increased | 37 | 3.9 | 0 | 25 | 3.7 | 0.5 |
| Hematology | ||||||
| Neutrophils decreased | 87 | 29 | 3.5 | 30 | 3.7 | 0.5 |
| Hemoglobin decreased | 84 | 2.6 | 0 | 34 | 0.5 | 0 |
| Lymphocytes decreased | 63 | 12 | 0.2 | 32 | 1.8 | 0 |
| Platelets decreased | 53 | 0.9 | 1.2 | 15 | 0 | 0 |
EMBER-3: VERZENIO in Combination with Imlunestrant in Advanced or Metastatic Breast Cancer
The safety of VERZENIO in combination with imlunestrant was evaluated in 535 patients with ER+, HER2- locally advanced or metastatic breast cancer previously treated with endocrine therapy with or without a prior CDK4/6 inhibitor in EMBER-3 [see Clinical Studies (14.2)]. Patients received VERZENIO 150 mg orally twice daily in combination with imlunestrant 400 mg orally once daily (N=208), or imlunestrant monotherapy 400 mg, once daily (n=327). Among patients who were treated with VERZENIO in combination with imlunestrant, the median duration of exposure was 7.7 months (range 1 day to 25.3 months).
Serious adverse reactions occurred in 21% of patients who received VERZENIO in combination with imlunestrant. Serious adverse reactions in >1% of patients included pneumonia (2.4%), abdominal pain, and renal failure (each 1.4%). Fatal adverse reactions occurred in 3.8% of patients who received VERZENIO in combination with imlunestrant, including pneumonia (1.4%), myocardial infarction, interstitial lung disease and sepsis (0.5%, each).
Permanent discontinuation of VERZENIO due to an adverse reaction occurred in 3.4% of patients. Adverse reactions which resulted in permanent discontinuation of VERZENIO included: increased ALT (1.4%), bile duct stone, diarrhea, drug-induced liver injury, prolonged QT interval, fatigue, maculo-papular rash, renal failure, and vomiting (0.5% each).
Dosage interruptions of VERZENIO due to an adverse reaction occurred in 59% of patients. Adverse reactions which required dosage interruptions of VERZENIO in ≥2% of patients included diarrhea (20%), neutropenia (10%), decreased neutrophils (8%), anemia (6%), nausea (6%), increased AST (2.4%), fatigue (2.4%), and vomiting (2.4%).
Dose reductions of VERZENIO due to an adverse reaction occurred in 42% of patients. Adverse reactions which required dose reductions of VERZENIO in ≥1% of patients included: diarrhea (20%), neutropenia (5%), nausea (3.4%), decreased neutrophils (3.4%), fatigue (2.4%), anemia (1.9%), increased AST (1.9%), increased ALT (1.4%).
The most common (≥10%) adverse reactions, including laboratory abnormalities were: decreased neutrophils, diarrhea, decreased hemoglobin, decreased lymphocytes, nausea, decreased platelets, fatigue, increased triglycerides, infections, increased AST, increased creatinine, increased ALT, vomiting, musculoskeletal pain, abdominal pain, decreased appetite, increased cholesterol, rash, cough, headache and decreased weight.
Table 14 and 15 summarizes the adverse reactions and laboratory abnormalities, respectively, in EMBER-3.
| ||||
| ||||
| Adverse Reactiona | VERZENIO plus Imlunestrant N=208 | Imlunestrant N=327 | ||
| All Grades % | Grades 3 or 4 % | All Grades % | Grades 3 or 4 % | |
| Gastrointestinal Disorders | ||||
| Diarrhea | 86 | 9 | 23 | 0.3 |
| Nausea | 51 | 1.9 | 18 | 0.3 |
| Vomiting | 32 | 0.5 | 10 | 0.6 |
| Abdominal painb | 24 | 1.9 | 11 | 0.3 |
| General Disorders and Administration Site Conditions | ||||
| Fatigueb | 41 | 5 | 24 | 0.3 |
| Infections and Infestations | ||||
| Infectionsb | 36 | 7 | 25 | 3.4 |
| Musculoskeletal Disorders | ||||
| Musculoskeletal painb | 25 | 1.4 | 31 | 2.8 |
| Metabolism and Nutrition Disorders | ||||
| Decreased appetiteb | 22 | 1 | 9 | 0.3 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Rashb | 14 | 1.4 | 4.9 | 0 |
| Respiratory, Thoracic and Mediastinal Disorders | ||||
| Coughb | 13 | 0 | 9 | 0 |
| Nervous System Disorders | ||||
| Headacheb | 10 | 0.5 | 9 | 0 |
| Investigations | ||||
| Decreased weight | 10 | 0 | 4.6 | 0 |
Clinically relevant adverse reactions (<10%) in patients who received VERZENIO in combination with imlunestrant included: constipation (9%), stomatitis (9%), fever (9%), urinary tract infection (8%), dizziness (8%), hot flush (6%), insomnia (6%), arrhythmia (6%), alopecia (5%), back pain (4.8%), venous thromboembolic event (4.8%) and interstitial lung disease or pneumonitis (2.9%).
| ||||
| ||||
| Lab Abnormalitya | VERZENIO plus Imlunestrant b | Imlunestrantb | ||
| All Grades % | Grades 3 or 4 % | All Grades % | Grades 3 or 4 % | |
| Hematology | ||||
| Neutrophils decreased | 86 | 21 | 28 | 4.3 |
| Hemoglobin decreased | 81 | 9 | 34 | 2.2 |
| Lymphocytes decreased | 58 | 9 | 29 | 2.2 |
| Platelets count decreased | 48 | 2.4 | 18 | 2.8 |
| Chemistry | ||||
| Triglycerides increased | 40 | 2.3 | 22 | 0 |
| AST increased | 36 | 2.5 | 27 | 1.9 |
| Creatinine increased | 36 | 1.1 | 6 | 0.3 |
| ALT increased | 33 | 5 | 22 | 1.3 |
| Cholesterol increased | 18 | 0 | 12 | 0.4 |
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 132 women with HR-positive, HER2-negative metastatic breast cancer whose disease progressed during or after endocrine therapy, had received a taxane in any setting, and who had received 1 or 2 prior chemotherapy regimens in the metastatic setting [see Clinical Studies (14.2)]. Patients received VERZENIO 200 mg orally twice daily. The median duration of exposure to VERZENIO was 4.5 months (range: 8 days – 20.4 months).
Serious adverse reactions occurred in 24% of patients who received VERZENIO. Serious adverse reactions in >2% of patients included infections (4.5%), increased creatinine (3%), dehydration, nausea, and abdominal pain (2.3%, each). Fatal adverse reactions occurred in 2.3% of patients who received VERZENIO including infection (1.5%) and pneumonitis (0.8%).
Permanent discontinuation of VERZENIO due to adverse reactions occurred in 8% of patients. Adverse reactions which resulted in permanent discontinuation of VERZENIO included abdominal pain, arterial thrombosis, increased AST, increased creatinine, chronic kidney disease, diarrhea, prolonged QT interval, fatigue, hip fracture, and lymphopenia (0.8% each).
Dosage interruptions of VERZENIO due to an adverse reaction occurred in 58% of patients. Adverse reactions which required dosage interruptions in ≥5% of patients were diarrhea (24%), neutropenia (16%), fatigue (10%), vomiting (6%), and nausea (5%).
Dose reductions of VERZENIO due to an adverse reaction occurred in 49% of patients. Adverse reactions which resulted in dose reductions in ≥5% of patients were diarrhea (20%), neutropenia (11%), and fatigue (9%).
The most common (≥20%) adverse reactions, including laboratory abnormalities, in patients treated with VERZENIO were: increased creatinine, diarrhea, decreased hemoglobin, fatigue, nausea, decreased appetite, decreased lymphocytes, decreased platelets, abdominal pain, vomiting, infections, increased ALT, increased AST and headache.
Adverse reactions are shown in Table 16 and laboratory abnormalities in Table 17.
| |||
| |||
Adverse Reactiona | 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 |
| General Disorders and Administration Site Conditions | |||
| Fatigueb | 65 | 13 | 0 |
| Pyrexia | 11 | 0 | 0 |
| Metabolism and Nutrition Disorders | |||
| Decreased appetite | 45 | 3.0 | 0 |
| Dehydration | 10 | 2.3 | 0 |
| Infections and Infestations | |||
| Infections | 31 | 4.5 | 0 |
| Nervous System Disorders | |||
| Headache | 20 | 0 | 0 |
| Dysgeusia | 12 | 0 | 0 |
| Dizziness | 11 | 0 | 0 |
| Respiratory, Thoracic and Mediastinal Disorders | |||
| Cough | 19 | 0 | 0 |
| Musculoskeletal and Connective Tissue Disorders | |||
| Arthralgia | 15 | 0 | 0 |
| Investigations | |||
| Weight decreased | 14 | 0 | 0 |
| Skin and Subcutaneous Tissue Disorders | |||
| Alopecia | 12 | 0 | 0 |
| VERZENIO N=132 | |||
| All Grades % | Grade 3 % | Grade 4 % | |
| Chemistry | |||
| Creatinine increased | 99 | 0.8 | 0 |
| ALT increased | 31 | 3.1 | 0 |
| AST increased | 30 | 3.8 | 0 |
| Hematology | |||
| Neutrophils decreased | 88 | 22 | 4.6 |
| Hemoglobin decreased | 69 | 0 | 0 |
| Lymphocytes decreased | 42 | 13 | 0.8 |
| Platelets decreased | 41 | 2.3 | 0 |
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)].
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.
Ketoconazole
Avoid concomitant use of ketoconazole. Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold [see Clinical Pharmacology (12.3)].
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 with concomitant use of strong CYP3A inhibitors. If a patient taking VERZENIO discontinues a strong CYP3A inhibitor, increase the VERZENIO dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor. Patients should avoid grapefruit products [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
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 [see Clinical Pharmacology (12.3)].
Refer to the Prescribing Information of the agents administered in combination with VERZENIO for pregnancy information.
Risk Summary
Based on findings in animals and its mechanism of action, VERZENIO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. 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 (see Data). 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.
Refer to the Prescribing Information of the agents administered in combination with VERZENIO for lactation information. When used in combination, advise patients to not breastfeed during treatment and for the longest post-treatment duration recommended in the prescribing information of any of the individual products.
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 3 weeks after the last dose.
Refer to the Prescribing Information of the agents administered in combination with VERZENIO for contraception and infertility information. When used in combination, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the prescribing information of the individual products.
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.
Contraception
Females
Advise females of reproductive potential to use effective contraception during VERZENIO treatment and for 3 weeks after the last dose.
Infertility
Males
Based on findings in animals, VERZENIO may impair fertility in males of reproductive potential [see Nonclinical Toxicology (13.1)].
The safety and effectiveness of VERZENIO have not been established in pediatric patients.
The safety and effectiveness of VERZENIO in combination with chemotherapy was assessed but not established in an open label, dose-finding trial (NCT04238819) in 43 pediatric patients aged 1 to < 17 years with relapsed/refractory solid tumors. No new safety signals were observed in pediatric patients in this study. Abemaciclib exposure in pediatric patients was within the range of the values previously observed in adults given a similar dose per body surface area.
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.
No overall differences in safety or effectiveness of VERZENIO as monotherapy or in combination with fulvestrant, tamoxifen, or an aromatase inhibitor have been observed between these patients and younger patients.
Of the 208 patients who received VERZENIO in combination with imlunestrant in EMBER-3, 90 patients were ≥65 years of age and 27 patients were ≥75 years of age. There was a higher rate of nausea in patients aged 65 years or older (59%) compared with younger patients (44%). The EMBER-3 study did not include sufficient numbers of patients 65 years of age and older with ESR1 mutations treated with VERZENIO in combination with imlunestrant to determine whether they respond differently than younger patients.
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 [see Clinical Pharmacology (12.3)].
Abemaciclib is a kinase inhibitor for oral administration. It is a white to yellow powder with the empirical formula C27H32F2N8 and a molecular weight 506.59.
The chemical name for abemaciclib is 2-Pyrimidinamine, N-[5-[(4-ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-. Abemaciclib has the following structure:
VERZENIO (abemaciclib) tablets are provided as immediate-release oval white, beige, or yellow tablets. Inactive ingredients are as follows: Excipients—microcrystalline cellulose 102, microcrystalline cellulose 101, lactose monohydrate, croscarmellose sodium, sodium stearyl fumarate, silicon dioxide. Color mixture ingredients—polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, iron oxide yellow, and iron oxide red.
Abemaciclib is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). These kinases are activated upon binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation. In vitro, continuous exposure to abemaciclib inhibited Rb phosphorylation and blocked progression from G1 into S phase of the cell cycle, resulting in senescence and apoptosis. In breast cancer xenograft models, abemaciclib dosed daily without interruption as a single agent or in combination with antiestrogens resulted in reduction of tumor size.
Cardiac Electrophysiology
Based on evaluation of the QTc interval in patients and in a healthy volunteer study, abemaciclib did not cause large mean increases (i.e., 20 ms) in the QTc interval.
The pharmacokinetics of abemaciclib were characterized in patients with solid tumors, including breast cancer, and in healthy subjects.
Following single and repeated twice daily dosing of 50 mg (0.3 times the approved recommended 150 mg dosage) to 200 mg of abemaciclib, the increase in plasma exposure (AUC) and Cmax was approximately dose proportional. Steady state was achieved within 5 days following repeated twice daily dosing, and the estimated geometric mean accumulation ratio was 2.3 (50% CV) and 3.2 (59% CV) based on Cmax and AUC, respectively.
Absorption
The absolute bioavailability of abemaciclib after a single oral dose of 200 mg is 45% (19% CV). The median Tmax of abemaciclib is 8.0 hours (range: 4.1-24.0 hours).
Effect of Food
A high-fat, high-calorie meal (approximately 800 to 1000 calories with 150 calories from protein, 250 calories from carbohydrate, and 500 to 600 calories from fat) administered to healthy subjects increased the AUC of abemaciclib plus its active metabolites by 9% and increased Cmax by 26%.
Distribution
In vitro, abemaciclib was bound to human plasma proteins, serum albumin, and alpha-1-acid glycoprotein in a concentration independent manner from 152 ng/mL to 5066 ng/mL. In a clinical study, the mean (standard deviation, SD) bound fraction was 96.3% (1.1) for abemaciclib, 93.4% (1.3) for M2, 96.8% (0.8) for M18, and 97.8% (0.6) for M20. The geometric mean systemic volume of distribution is approximately 690.3 L (49% CV).
In patients with advanced cancer, including breast cancer, concentrations of abemaciclib and its active metabolites M2 and M20 in cerebrospinal fluid are comparable to unbound plasma concentrations.
Elimination
The geometric mean hepatic clearance (CL) of abemaciclib in patients was 26.0 L/h (51% CV), and the mean plasma elimination half-life for abemaciclib in patients was 18.3 hours (72% CV).
Metabolism
Hepatic metabolism is the main route of clearance for abemaciclib. Abemaciclib is metabolized to several metabolites primarily by cytochrome P450 (CYP) 3A4, with formation of N-desethylabemaciclib (M2) representing the major metabolism pathway. Additional metabolites include hydroxyabemaciclib (M20), hydroxy-N-desethylabemaciclib (M18), and an oxidative metabolite (M1). M2, M18, and M20 are equipotent to abemaciclib and their AUCs accounted for 25%, 13%, and 26% of the total circulating analytes in plasma, respectively.
Excretion
After a single 150 mg oral dose of radiolabeled abemaciclib, approximately 81% of the dose was recovered in feces and approximately 3% recovered in urine. The majority of the dose eliminated in feces was metabolites.
Specific Populations
Age, Gender, and Body Weight
Based on a population pharmacokinetic analysis in patients with cancer, age (range 24-91 years), gender (134 males and 856 females), and body weight (range 36-175 kg) had no effect on the exposure of abemaciclib.
Patients with Renal Impairment
In a population pharmacokinetic analysis of 990 individuals, in which 381 individuals had mild renal impairment (60 mL/min ≤ CLcr <90 mL/min) and 126 individuals had moderate renal impairment (30 mL/min ≤ CLcr <60 mL/min), mild and moderate renal impairment had no effect on the exposure of abemaciclib [see Use in Specific Populations (8.6)]. The effect of severe renal impairment (CLcr <30 mL/min) on pharmacokinetics of abemaciclib is unknown.
Patients with Hepatic Impairment
Following a single 200 mg oral dose of abemaciclib, the relative potency adjusted unbound AUC0-INF of abemaciclib plus its active metabolites (M2, M18, M20) in plasma increased 1.2-fold in subjects with mild hepatic impairment (Child-Pugh A, n=9), 1.1-fold in subjects with moderate hepatic impairment (Child-Pugh B, n=10), and 2.4-fold in subjects with severe hepatic impairment (Child-Pugh C, n=6) relative to subjects with normal hepatic function (n=10) [see Use in Specific Populations (8.7)]. In subjects with severe hepatic impairment, the mean plasma elimination half-life of abemaciclib increased to 55 hours compared to 24 hours in subjects with normal hepatic function.
Drug Interaction Studies
Effects of Other Drugs on Abemaciclib
Strong CYP3A Inhibitors: Ketoconazole (a strong CYP3A inhibitor) is predicted to increase the AUC of abemaciclib by up to 16-fold.
Coadministration of 500 mg twice daily doses of clarithromycin (a strong CYP3A inhibitor) with a single 50 mg dose of VERZENIO (0.3 times the approved recommended 150 mg dosage) increased the relative potency adjusted unbound AUC0-INF of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold relative to abemaciclib alone in cancer patients.
Moderate CYP3A Inhibitors: Verapamil and diltiazem (moderate CYP3A inhibitors) are predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6-fold and 2.4-fold, respectively.
Strong CYP3A Inducers: Coadministration of 600 mg daily doses of rifampin (a strong CYP3A inducer) with a single 200 mg dose of VERZENIO decreased the relative potency adjusted unbound AUC0-INF of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 70% in healthy subjects.
Moderate CYP3A Inducers: Efavirenz, bosentan, and modafinil (moderate CYP3A inducers) are predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29%, respectively.
Loperamide: Co-administration of a single 8 mg dose of loperamide with a single 400 mg dose of abemaciclib in healthy subjects increased the relative potency adjusted unbound AUC0-INF of abemaciclib plus its active metabolites (M2 and M20) by 12%, which is not considered clinically relevant.
Endocrine Therapies: In clinical studies in patients with breast cancer, there was no clinically relevant effect of fulvestrant, imlunestrant, anastrozole, letrozole, exemestane, or tamoxifen on abemaciclib pharmacokinetics.
Effects of Abemaciclib on Other Drugs
Loperamide: In a clinical drug interaction study in healthy subjects, coadministration of a single 8 mg dose of loperamide with a single 400 mg abemaciclib (2.7 times the approved recommended 150 mg dosage) increased loperamide AUC0-INF by 9% and Cmax by 35% relative to loperamide alone. These increases in loperamide exposure are not considered clinically relevant.
Metformin: In a clinical drug interaction study in healthy subjects, coadministration of a single 1000 mg dose of metformin, a clinically relevant substrate of renal OCT2, MATE1, and MATE2-K transporters, with a single 400 mg dose of abemaciclib (2.7 times the approved recommended 150 mg dosage) increased metformin AUC0-INF by 37% and Cmax by 22% relative to metformin alone. Abemaciclib reduced the renal clearance and renal secretion of metformin by 45% and 62%, respectively, relative to metformin alone, without any effect on glomerular filtration rate (GFR) as measured by iohexol clearance and serum cystatin C.
Endocrine Therapies: In clinical studies in patients with breast cancer, there was no clinically relevant effect of abemaciclib on the pharmacokinetics of fulvestrant, imlunestrant, anastrozole, letrozole, exemestane, or tamoxifen.
CYP Metabolic Pathways: In a clinical drug interaction study in patients with cancer, multiple doses of abemaciclib (200 mg twice daily for 7 days) did not result in clinically meaningful changes in the pharmacokinetics of CYP1A2, CYP2C9, CYP2D6 and CYP3A4 substrates. Abemaciclib is a substrate of CYP3A4, and time-dependent changes in pharmacokinetics of abemaciclib as a result of autoinhibition of its metabolism were not observed.
In Vitro Studies
Transporter Systems: Abemaciclib and its major active metabolites inhibit the renal transporters OCT2, MATE1, and MATE2-K at concentrations achievable at the approved recommended dosage. The observed serum creatinine increase in clinical studies with abemaciclib is likely due to inhibition of tubular secretion of creatinine via OCT2, MATE1, and MATE2-K [see Adverse Effects (6.1)]. Abemaciclib and its major metabolites at clinically relevant concentrations do not inhibit the hepatic uptake transporters OCT1, OATP1B1, and OATP1B3 or the renal uptake transporters OAT1 and OAT3.
Abemaciclib is a substrate of P-gp and BCRP. Abemaciclib and its major active metabolites, M2 and M20, are not substrates of hepatic uptake transporters OCT1, organic anion transporting polypeptide 1B1 (OATP1B1), or OATP1B3.
Abemaciclib inhibits P-gp and BCRP. The clinical consequences of this finding on sensitive P-gp and BCRP substrates are unknown.
P-gp and BCRP Inhibitors: In vitro, abemaciclib is a substrate of P-gp and BCRP. The effect of P-gp or BCRP inhibitors on the pharmacokinetics of abemaciclib has not been studied.
Abemaciclib was assessed for carcinogenicity in a 2-year rat study. Abemaciclib was not carcinogenic in male and female rats at oral doses up to 3 mg/kg/day (approximately 1 time the exposure at the maximum recommended human dose based on AUC).
Abemaciclib and its active human metabolites M2 and M20 were not mutagenic in a bacterial reverse mutation (Ames) assay or clastogenic in an in vitro chromosomal aberration assay in Chinese hamster ovary cells or human peripheral blood lymphocytes. Abemaciclib, M2, and M20 were not clastogenic in an in vivo rat bone marrow micronucleus assay.
Abemaciclib may impair fertility in males of reproductive potential. In repeat-dose toxicity studies up to 3-months duration, abemaciclib-related findings in the testis, epididymis, prostate, and seminal vesicle at doses ≥10 mg/kg/day in rats and ≥0.3 mg/kg/day in dogs included decreased organ weights, intratubular cellular debris, hypospermia, tubular dilatation, atrophy, and degeneration/necrosis. These doses in rats and dogs resulted in approximately 2 and 0.02 times, respectively, the exposure (AUC) in humans at the maximum recommended human dose. In a rat male fertility study, abemaciclib had no effects on mating and fertility at oral doses up to 10 mg/kg/day (approximately 2 times the exposure at the maximum recommended human dose based on AUC).
In a rat female fertility and early embryonic development study, abemaciclib did not affect mating and fertility at doses up to 20 mg/kg/day (approximately 3 times the exposure at the maximum recommended human dose based on AUC).
In repeat-dose toxicity studies up to 6-months duration, oral administration of abemaciclib resulted in retinal atrophy of the eyes in mice at a dose of 150 mg/kg/day (approximately 10 times the exposure at the maximum recommended human dose based on AUC) and in rats at a dose of 30 mg/kg/day (approximately 5 times the exposure at the maximum recommended human dose based on AUC). In a 2-year rat carcinogenicity study, oral administration of abemaciclib resulted in retinal atrophy in the eyes at doses ≥0.3 mg/kg/day (approximately 0.05 times the exposure at the maximum recommended human dose based on AUC).
VERZENIO in Combination with Endocrine Therapy (monarchE)
Patients with HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence
The efficacy of VERZENIO in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) was evaluated in monarchE (NCT03155997), a randomized, open-label, two cohort, multicenter study in 5637 adults with HR-positive, HER2-negative, node-positive, resected, early breast cancer with clinical and pathological features consistent with a high risk of disease recurrence of which 5120 (91%) were randomized in cohort 1. To be enrolled, patients had to have HR-positive HER2-negative early breast cancer with tumor involvement in at least 1 axillary lymph node (pALN) and to be enrolled in cohort 1 had to have either:
Patients enrolled in cohort 2 could not have met the eligibility criteria for cohort 1. To be enrolled in cohort 2, patients had to have 1-3 pALN and Ki-67 score ≥20%. Breast tumor samples were tested at central sites using the Ki-67 IHC MIB-1 pharmDx (Dako Omnis) assay to establish if the Ki-67 score was ≥20%.
Patients were randomized 1:1 to receive VERZENIO 150 mg orally once daily for 2 years in combination with endocrine therapy (tamoxifen or an aromatase inhibitor); or endocrine therapy alone. Randomization was stratified by prior treatment (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy); menopausal status (premenopausal versus postmenopausal); and region (North America/Europe versus Asia versus other). Men were stratified as postmenopausal. After the end of the study treatment period, standard adjuvant endocrine therapy was continued for a duration of at least 5 years if deemed medically appropriate.
The major efficacy outcome for VERZENIO in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) was invasive disease–free survival (IDFS). IDFS was defined as the time from randomization to the first occurrence of: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, or death attributable to any cause. Overall survival (OS) was an additional outcome measure.
A statistically significant difference in IDFS was observed in the intent-to-treat (ITT) population which was primarily attributed to the patients treated in cohort 1.
Of the 5120 patients randomized in cohort 1, the median age was 51 years (range, 22-89 years), 99% were women, 70% were White, 24% were Asian, 1.7% were Black or African American, 2.1% were American Indian or Alaska Native, and 0.1% were Native Hawaiian or Other Pacific Islander; 8% were Hispanic/Latino and 92% were not Hispanic/Latino and 0.2% were not reported/missing. Forty-three percent of patients were premenopausal. Most patients received prior chemotherapy (37% neoadjuvant, 59% adjuvant) and prior radiotherapy (96%). Sixty-five percent of the patients had 4 or more positive lymph nodes with 22% having ≥10 positive lymph nodes, 41% had Grade 3 tumor, and 24% had pathological tumor size ≥50 mm. The majority of patients (99%) had estrogen receptor positive disease and 87% had progesterone receptor positive disease. Initial endocrine therapy received by patients included letrozole (39%), tamoxifen (31%), anastrozole (22%), or exemestane (8%).
Efficacy results for cohort 1 are summarized in Table 18 and Figure 1.
| ||
| VERZENIO Plus Tamoxifen or an Aromatase Inhibitor N=2555 | Tamoxifen or an Aromatase Inhibitor N=2565 | |
| Invasive Disease–Free Survival (IDFS) | ||
| Number of patients with an event, n (%) | 317 (12) | 474 (18) |
| Hazard ratio (95% CI) | 0.65 (0.57, 0.75) | |
| IDFS at 48 months, % (95% CI) | 85.5 (83.8, 87.0) | 78.6 (76.7, 80.4) |
Figure 1: Kaplan-Meier Curves of Invasive Disease–Free Survival VERZENIO plus Tamoxifen or an Aromatase Inhibitor versus Tamoxifen or an Aromatase Inhibitor in Cohort 1 (monarchE)
A final OS analysis was conducted after 630 death events were observed in cohort 1. Exploratory OS results showed a HR of 0.84 (95% CI: 0.71, 0.98) for patients treated with VERZENIO plus Tamoxifen or an Aromatase Inhibitor compared with patients treated with Tamoxifen or an Aromatase Inhibitor in cohort 1.
VERZENIO in Combination with an Aromatase Inhibitor (Anastrozole or Letrozole) (MONARCH 3)
Postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer with no prior systemic therapy in this disease setting
The efficacy of VERZENIO in combination with an aromatase inhibitor was evaluated in MONARCH 3 (NCT02246621), a randomized, double-blinded, placebo-controlled, multicenter study in 493 postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with a nonsteroidal aromatase inhibitor as initial endocrine-based therapy, including patients not previously treated with systemic therapy for breast cancer. Patients were randomized 2:1 to VERZENIO 150 mg orally twice daily in combination with an aromatase inhibitor or placebo in combination with an aromatase inhibitor. Randomization was stratified by disease site (visceral, bone only, or other) and by prior (neo)adjuvant endocrine therapy (aromatase inhibitor versus other versus no prior endocrine therapy). Patients were treated until disease progression or unacceptable toxicity.
The major efficacy outcome for VERZENIO in combination with an aromatase inhibitor was progression free survival (PFS) by investigator assessment using Response Evaluation Criteria (RECIST) v1.1. Other efficacy measures included OS and objective response rate (ORR).
The median age was 63 years (range, 32-88 years), 45% age 65 or older; 58% White, 30% Asian, 1.6% Black or African American, 1.4% American Indian or Alaska Native, 0.2% Native Hawaiian or Other Pacific Islander, and 0.4% multiple races, and race was not reported for 7.9%; 8.9% were Hispanic/Latino and 72% were not Hispanic/Latino and 19% not reported/missing; and baseline ECOG performance status was 0 (60%), or 1 (40%). Most patients had visceral metastasis (53%) at baseline and 22% had bone-only disease. Of the patients enrolled, 51% had received prior systemic therapy and 39% of patients had received chemotherapy. Overall, 80% of patients received letrozole as investigator's choice aromatase inhibitor and 20% received anastrozole.
Efficacy results are summarized in Table 19 and Figure 2. PFS assessment based on a blinded independent radiologic review was consistent with the investigator assessment. Consistent PFS results were observed across patient stratification subgroups of disease site and prior (neo)adjuvant endocrine therapy.
| ||
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| VERZENIO plus Anastrozole or Letrozole | Placebo plus Anastrozole or Letrozole | |
| Progression-Free Survival | N=328 | N=165 |
| Number of patients with an event, n (%) | 138 (42) | 108 (65) |
| Median in months (95% CI) | 28.2 (23.5, NR) | 14.8 (11.2, 19.2) |
| Hazard ratio (95% CI) | 0.54 (0.42, 0.70) | |
| p-value | <0.0001 | |
| Overall Survival | N=328 | N=165 |
| Number of patients with an event, n (%) | 198 (60) | 116 (70) |
| Median in months (95% CI) | 66.8 (59.2, 74.8) | 53.7 (44.7, 59.3) |
| Hazard ratio (95% CI) | 0.80 (0.64, 1.02) | |
| p-value | NS | |
| Objective Response for Patients with Measurable Diseasea | N=267 | N=132 |
| Objective response rate, n (%)a,b | 148 (55) | 53 (40) |
| 95% CI | 49, 61 | 32, 49 |
Figure 2: Kaplan-Meier Curves of Progression-Free Survival: VERZENIO plus Anastrozole or Letrozole versus Placebo plus Anastrozole or Letrozole in Intent-to-Treat Population (MONARCH 3)
VERZENIO in Combination with Fulvestrant (MONARCH 2)
Patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression on or after prior adjuvant or metastatic endocrine therapy
The efficacy of VERZENIO in combination with fulvestrant was evaluated in MONARCH 2 (NCT02107703), a randomized, placebo-controlled, multicenter study in 669 women with HR-positive, HER2-negative metastatic breast cancer with disease progression following endocrine therapy who had not received chemotherapy in the metastatic setting. Patients were randomized 2:1 to VERZENIO 150 mg orally twice daily or placebo orally twice daily in combination with fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then on day 1 of cycle 2 and beyond (28-day cycles). Randomization was stratified by disease site (visceral, bone only, or other) and by sensitivity to prior endocrine therapy (primary or secondary resistance). Primary endocrine therapy resistance was defined as relapse while on the first 2 years of adjuvant endocrine therapy or progressive disease within the first 6 months of first line endocrine therapy for metastatic breast cancer. Pre/perimenopausal women were enrolled in the study and received the gonadotropin-releasing hormone agonist goserelin for at least 4 weeks prior to and for the duration of MONARCH 2. Patients remained on continuous treatment until development of progressive disease or unmanageable toxicity.
The major efficacy outcome for VERZENIO in combination with fulvestrant was PFS by investigator assessment using RECIST v1.1. Other efficacy measures included OS and ORR.
The median age was 60 years (range, 32-91 years), 37% age 65 or older, 56% White, 32% Asian, 3.9% American Indian or Alaska Native, 2.1% Black or African American, and race was not reported for 6.3%; 12% were Hispanic/Latino and 70% were not Hispanic/Latino, 18% not reported/missing; ECOG performance status was 0 (60%), 1 (39%) or 2 (0.1%). Most patients had visceral disease (56%), 27% had bone-only disease, and 20% had de novo metastatic disease. Twenty-five percent (25%) of patients had primary endocrine therapy resistance. Seventeen percent (17%) of patients were pre- or perimenopausal.
Efficacy results are summarized in Table 20, Figure 3, and Figure 4. PFS assessment based on a blinded independent radiologic review was consistent with the investigator assessment. Consistent results were observed across patient stratification subgroups of disease site and endocrine therapy resistance for PFS and OS.
| ||
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| ||
| VERZENIO plus Fulvestrant | Placebo plus Fulvestrant | |
| Progression-Free Survival (Investigator Assessment) | N=446 | N=223 |
| Number of patients with an event, n (%) | 222 (50) | 157 (70) |
| Median in months (95% CI) | 16.4 (14.4, 19.3) | 9.3 (7.4, 12.7) |
| Hazard ratio (95% CI)a | 0.55 (0.45, 0.68) | |
| p-valuea | p<.0001 | |
| Overall Survivalb | ||
| Number of deaths, n (%) | 211 (47) | 127 (57) |
| Median OS in months (95% CI) | 46.7 (39.2, 52.2) | 37.3 (34.4, 43.2) |
| Hazard ratio (95% CI)a | 0.76 (0.61, 0.95) | |
| p-valuea | p=.0137 | |
| Objective Response for Patients with Measurable Disease | N=318 | N=164 |
| Objective response rate, n (%)c | 153 (48) | 35 (21) |
| 95% CI | 43, 54 | 15, 28 |
Figure 3: Kaplan-Meier Curves of Progression-Free Survival: VERZENIO plus Fulvestrant versus Placebo plus Fulvestrant (MONARCH 2)
Figure 4: Kaplan-Meier Curves of Overall Survival: VERZENIO plus Fulvestrant versus Placebo plus Fulvestrant (MONARCH 2)
VERZENIO in Combination with Imlunestrant in Advanced or Metastatic Breast Cancer (EMBER-3)
The efficacy of VERZENIO in combination with imlunestrant was evaluated in EMBER-3 (NCT04975308), a randomized, open-label, active-controlled, multicenter trial that enrolled 874 adult patients with ER+, HER2- locally advanced or metastatic breast cancer of which 323 patients had ESR1 mutations (ESR1m), who were previously treated with an aromatase inhibitor either alone or in combination with a CDK4/6 inhibitor. Patients were excluded if they were eligible to receive a PARP inhibitor. Patients were required to have progressed:
Patients were randomized 1:1:1 to
Randomization was stratified by previous treatment with CDK4/6 inhibitor (yes vs no), presence of visceral metastasis (yes vs no), and region (East Asia vs North America/Western Europe vs Others). ESR1m status was determined by blood circulating tumor deoxyribonucleic acid (ctDNA) analysis using the Guardant360 CDx assay and was limited to specific ESR1 mutations in the ligand binding domain. Patients were treated until disease progression or unacceptable toxicity.
The major efficacy outcome for VERZENIO in combination with imlunestrant was investigator-assessed PFS according to RECIST v1.1 in the overall population. Other efficacy measures included OS, BIRC-assessed PFS, and ORR. While the comparison of PFS between VERZENIO in combination with imlunestrant and imlunestrant monotherapy in the overall population was statistically significant, a PFS improvement was not demonstrated for imlunestrant monotherapy compared to investigator's choice of endocrine therapy in either the overall or ESR1m not detected populations, indicating that the benefit for imlunestrant monotherapy was only observed in the ESR1m population. Therefore, exploratory analyses of PFS, OS and ORR in the ESR1m population comparing VERZENIO in combination with imlunestrant and imlunestrant monotherapy were performed.
Among the patients on VERZENIO in combination with imlunestrant or the imlunestrant monotherapy arm who were positive for ESR1m (n= 159), the median age was 62 years (range: 31-85 years), all patients were female, of which 12% were pre/perimenopausal; 60% were White, 27% Asian, 5% Black, 0.6% were American Indian or Alaskan Native, 0.6% multiple races, 7% missing, 12% were Hispanic/Latino, 75% not Hispanic/Latino, 13% not reported/missing; and all patients had a baseline ECOG performance status of 0 (66%) or 1 (34%). Most patients had visceral metastasis (58%) at baseline. Of the patients enrolled, all received a prior line of endocrine therapy and 81% had received one line of endocrine therapy in the advanced or metastatic setting. Overall, 79% of patients were treated with a prior CDK4/6 inhibitor, 4.4% were treated in the adjuvant setting and 74% were treated in the advanced or metastatic setting. Among the patients who had received prior CDK 4/6 inhibitors, the specific CDK 4/6 inhibitor was palbociclib 65%, ribociclib 28%, and abemaciclib 6%.
The exploratory analyses results in the ESR1m population are summarized in Table 21 and Figure 5. PFS assessments in ESR1m population based on a BIRC were consistent with the investigator assessment. At the time of interim analysis, overall survival data was immature with 35% of deaths in the ESR1m population.
| ||
| ||
| ||
| VERZENIO plus Imlunestrant N=67 | Imlunestrant N=92 | |
| Progression-free Survival (PFS)a,b | ||
| Number of PFS Events, n (%) | 36 (54) | 71 (77) |
| Median in months (95% CI) | 11.1 (7.4, 13.7) | 5.5 (3.8, 7.2) |
| Hazard Ratio (95% CI)c | 0.53 (0.35, 0.80) | |
| Objective Response Rateb | ||
| Patients with Measurable Disease | 54 | 74 |
| ORR, % (95% CI) | 35 (22, 48) | 15 (7, 23) |
| Complete response rate, % | 1.9 | 1.4 |
| Partial response rate, % | 33 | 14 |
Figure 5: Kaplan-Meier Plot of Investigator-Assessed PFS for Patients with ESR1m, Treated with VERZENIO in Combination with Imlunestrant or Imlunestrant Monotherapy in EMBER-3
VERZENIO Administered as a Monotherapy in Metastatic Breast Cancer (MONARCH 1)
Patients with HR-positive, HER2-negative breast cancer who received prior endocrine therapy and 1-2 chemotherapy regimens in the metastatic setting
The efficacy of VERZENIO monotherapy was evaluated in MONARCH 1 (NCT02102490), a single-arm, open-label, multicenter study in 132 women with measurable HR-positive, HER2-negative metastatic breast cancer whose disease progressed during or after endocrine therapy, had received a taxane in any setting, and who received 1 or 2 prior chemotherapy regimens in the metastatic setting. Patients received VERZENIO 200 mg orally twice daily on a continuous schedule until development of progressive disease or unmanageable toxicity.
The major efficacy outcome was ORR. Duration of response (DoR) was another efficacy measure.
The median age was 58 years (range, 36-89 years), 32% age 65 or older; 85% White, 4.5% Black or African American, 1.5% Asian, and race was not reported for 9.1%; 6.1% were Hispanic/Latino and 85% were not Hispanic/Latino, and 9.1% not reported/missing; ECOG performance status was 0 (55%) or 1 (45%). The median duration of metastatic disease was 27.6 months. Ninety percent (90%) of patients had visceral metastases, and 51% of patients had 3 or more sites of metastatic disease. Fifty-one percent (51%) of patients had one line of chemotherapy in the metastatic setting. Sixty-nine percent (69%) of patients had received a taxane-based regimen in the metastatic setting and 55% had received capecitabine in the metastatic setting.
Efficacy results are summarized in Table 22.
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| ||
| ||
| VERZENIO 200 mg N=132 | ||
| Investigator Assessed | Independent Review | |
| Objective Response Ratea,b, n (%) | 26 (20) | 23 (17) |
| 95% CI | 13, 28 | 11, 25 |
| Median Duration of Response in months | 8.6 | 7.2 |
| 95% CI | 5.8, 10.2 | 5.6, NR |
How Supplied
| Strength | Description | Blister Pack Configuration | NDC |
| 200 mg | Oval beige tablet with "Lilly" debossed on one side and "200" on the other side | Blister pack containing 14 tablets (7-day supply) | 0002-6216-54 |
| 150 mg | Oval yellow tablet with "Lilly" debossed on one side and "150" on the other side | Blister pack containing 14 tablets (7-day supply) | 0002-5337-54 |
| 100 mg | Oval white to practically white tablet with "Lilly" debossed on one side and "100" on the other side | Blister pack containing 14 tablets (7-day supply) | 0002-4815-54 |
| 50 mg | Oval beige tablet with "Lilly" debossed on one side and "50" on the other side | Blister pack containing 14 tablets (7-day supply) | 0002-4483-54 |
Storage and Handling
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Diarrhea
VERZENIO may cause diarrhea, which may be severe in some cases [see Warnings and Precautions (5.1)].
Neutropenia
Advise patients of the possibility of developing neutropenia and to immediately contact their healthcare provider should they develop a fever, particularly in association with any signs of infection [see Warnings and Precautions (5.2)].
Interstitial Lung Disease/Pneumonitis
Advise patients to immediately report new or worsening respiratory symptoms [see Warnings and Precautions (5.3)].
Hepatotoxicity
Inform patients of the signs and symptoms of hepatotoxicity. Advise patients to contact their healthcare provider immediately for signs or symptoms of hepatotoxicity [see Warnings and Precautions (5.4)].
Venous Thromboembolism
Advise patients to immediately report any signs or symptoms of thromboembolism such as pain or swelling in an extremity, shortness of breath, chest pain, tachypnea, and tachycardia [see Warnings and Precautions (5.5)].
Embryo-Fetal Toxicity
Lactation
Infertility
Inform males of reproductive potential that VERZENIO may impair fertility [see Use in Specific Populations (8.3)].
Drug Interactions
Dosing Instructions
Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA
Copyright © 2017, 2026, Eli Lilly and Company. All rights reserved.
Pat.: www.lilly.com/patents
VER-0012-USPI-20260918
|
| ||||
| PATIENT INFORMATION VERZENIO® (ver-ZEN-ee-oh) (abemaciclib) tablets | |||||
What is the most important information I should know about VERZENIO?
| |||||
| If you develop serious side effects during treatment with VERZENIO, your healthcare provider may reduce your dose, temporarily stop, or completely stop treatment with VERZENIO. See “What are the possible side effects of VERZENIO?” for more information about side effects. | |||||
| What is VERZENIO? VERZENIO is a prescription medicine used in adults:
| |||||
| When VERZENIO is used in combination with fulvestrant, tamoxifen, imlunestrant, or an aromatase inhibitor, also read the Patient Information or Medication Guide for the prescribed product if available. Ask your healthcare provider if you are not sure. It is not known if VERZENIO is safe and effective in children. | |||||
Before taking VERZENIO, tell your healthcare provider about all of your medical conditions, including if you:
| |||||
| Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VERZENIO may affect the way other medicines work, and other medicines may affect how VERZENIO works, causing serious side effects. Especially tell your healthcare provider if you take a medicine that contains ketoconazole. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. | |||||
How should I take VERZENIO?
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What should I avoid during treatment with VERZENIO?
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What are the possible side effects of VERZENIO? | |||||
The most common side effects of VERZENIO include:
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| VERZENIO may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if this is a concern for you. These are not all of the possible side effects of VERZENIO. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. | |||||
How should I store VERZENIO?
| |||||
| Keep VERZENIO and all medicines out of the reach of children. | |||||
| General information about the safe and effective use of VERZENIO. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use VERZENIO for a condition for which it was not prescribed. Do not give VERZENIO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for more information about VERZENIO that is written for health professionals. | |||||
| What are the ingredients in VERZENIO? Active ingredient: abemaciclib Inactive ingredients: microcrystalline cellulose 102, microcrystalline cellulose 101, lactose monohydrate, croscarmellose sodium, sodium stearyl fumarate, silicon dioxide. Color mixture ingredients: polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, iron oxide yellow, iron oxide red. Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA Copyright © 2017, 2026, Eli Lilly and Company. All rights reserved. VER-0006-PPI-20260918 For more information, go to www.verzenio.com or call 1-800-545-5979.
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PACKAGE CARTON – VERZENIO 50 mg 14ct
14 tablets
NDC 0002-4483-54
Rx only
Verzenio®
(abemaciclib) tablets
50 mg dose
7-Day Supply
This 50 mg Dose Pack contains fourteen 50 mg tablets.
LIFT TO OPEN
Lilly
PACKAGE CARTON – VERZENIO 100 mg 14ct
14 tablets
NDC 0002-4815-54
Rx only
Verzenio®
(abemaciclib) tablets
100 mg dose
7-Day Supply
This 100 mg Dose Pack contains fourteen 100 mg tablets.
LIFT TO OPEN
Lilly
PACKAGE CARTON – VERZENIO 150 mg 14ct
14 tablets
NDC 0002-5337-54
Rx only
Verzenio®
(abemaciclib) tablets
150 mg dose
7-Day Supply
This 150 mg Dose Pack contains fourteen 150 mg tablets.
LIFT TO OPEN
Lilly
PACKAGE CARTON – VERZENIO 200 mg 14ct
14 tablets
NDC 0002-6216-54
Rx only
Verzenio®
(abemaciclib) tablets
200 mg dose
7-Day Supply
This 200 mg Dose Pack contains fourteen 200 mg tablets.
LIFT TO OPEN
Lilly
| Product concept | Relation | Version | Effective |
|---|---|---|---|
| 54b69052-dc0f-43b6-aed1-9c546fcb601c | Product name | 1 | 20171115 |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 0002-4483-54 | EA - Each | 0002-4483 | 26f85b60-ad96-407d-9943-c4aeff79e625 | 1 | 2017-11-06 |
| 0002-4815-54 | EA - Each | 0002-4815 | ef779850-d1f8-4f21-a180-6a737da5b4a6 | 1 | 2017-11-06 |
| 0002-5337-54 | EA - Each | 0002-5337 | aa15735c-3ca2-4898-b290-1f3e249fa4a1 | 1 | 2017-11-06 |
| 0002-6216-54 | EA - Each | 0002-6216 | 21809231-76c6-4f7b-8505-ce11d5f48f61 | 1 | 2017-11-06 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 0002-4483 | 0002-4483-54, 0002-4483-62 |
| 0002-4815 | 0002-4815-54, 0002-4815-62 |
| 0002-5337 | 0002-5337-54, 0002-5337-63, 0002-5337-62 |
| 0002-6216 | 0002-6216-54 |
Every source-derived ingredient row is available through these pages.
| Version | Effective date | Source | Hydrated |
|---|---|---|---|
| 30 | 2026-07-13 | daily-update | 2026-07-24 05:10:23 |
| 27 | 2025-08-25 | full-release | 2026-05-31 21:41:20 |
All distinct exact application/product contexts derived from this label’s complete NDC list are paginated below.
| Application-product | Trade name | Ingredient | Strength | Dosage form / route | TE codes | RLD / RS | Approval date |
|---|---|---|---|---|---|---|---|
| N208716-001 | VERZENIO | ABEMACICLIB | 50MG | TABLET / ORAL | RLD | 2017-09-28 | |
| N208716-002 | VERZENIO | ABEMACICLIB | 100MG | TABLET / ORAL | RLD | 2017-09-28 | |
| N208716-003 | VERZENIO | ABEMACICLIB | 150MG | TABLET / ORAL | RLD | 2017-09-28 | |
| N208716-004 | VERZENIO | ABEMACICLIB | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 |
| Application-product | Patent | Expiration | Use code | Coverage / status | Submission date |
|---|---|---|---|---|---|
| N208716-001 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 |
| N208716-001 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 |
| N208716-001 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 |
| N208716-001 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 |
| N208716-002 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 |
| N208716-002 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 |
| N208716-002 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 |
| N208716-002 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 |
| N208716-003 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 |
| N208716-003 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 |
| N208716-003 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 |
| N208716-003 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 |
| N208716-004 | 7855211 | 2031-09-28 | U-1981 | Drug substance, Drug product | 2017-10-16 |
| N208716-004 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 |
| N208716-004 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 |
| N208716-004 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 |
| N208716-004 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 |
Observed FDA ZIP history: Each table is queried independently by exact application/product key from successfully parsed Orange Book snapshots. Capture times identify archived source observations; absence or a change between snapshots is not inferred. FDA publication files that were not recoverable as structured ZIP data are not represented as states.
| Captured | Edition | Application-product | Trade name | Strength | Dosage form / route | Product TE source text | RLD / RS | Approval date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | 84e616aacf4f… | |
| 2026-08-18 06:07:40 | 2026-07 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | caaa826d4ba7… | |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | 011fe1cb6892… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | 31067a03dcf5… | |
| 2025-08-23 18:47 UTC | 2025-08 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | 6a471c1ec25d… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | fd3edfee7708… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | b8a1b40f171c… | |
| 2025-02-26 10:13 UTC · 3 captures of this ZIP | 2025-02 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | b8a1b40f171c… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | 03ed91905a0d… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | 03ed91905a0d… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | 03ed91905a0d… | |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | 03ed91905a0d… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | 2680178bc6a6… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | 2680178bc6a6… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | 2680178bc6a6… | |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | 2680178bc6a6… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-001 | VERZENIO | 50MG | TABLET / ORAL | RLD | 2017-09-28 | 5bbf6a4d5a75… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-002 | VERZENIO | 100MG | TABLET / ORAL | RLD | 2017-09-28 | 5bbf6a4d5a75… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-003 | VERZENIO | 150MG | TABLET / ORAL | RLD | 2017-09-28 | 5bbf6a4d5a75… | |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-004 | VERZENIO | 200MG | TABLET / ORAL | RLD, RS | 2017-09-28 | 5bbf6a4d5a75… |
| Captured | Edition | Application-product | Patent | Expiration | Use code | Coverage / status | Submission date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|
| 2026-09-14 22:38:34 | 2026-08 | N208716-001 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-001 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-001 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-001 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-002 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-002 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-002 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-002 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-003 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-003 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-003 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-003 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-004 | 7855211 | 2031-09-28 | U-1981 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-004 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-004 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-004 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-09-14 22:38:34 | 2026-08 | N208716-004 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 | 84e616aacf4f… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-001 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-001 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-001 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-001 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-002 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-002 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-002 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-002 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-003 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-003 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-003 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-003 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-004 | 7855211 | 2031-09-28 | U-1981 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-004 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-004 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-004 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-08-18 06:07:40 | 2026-07 | N208716-004 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 | caaa826d4ba7… |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-001 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-001 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-001 | 7855211 | 2031-09-28 | U-3265 | Drug substance, Drug product | 2017-10-16 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-001 | 7855211 | 2031-09-28 | U-3242 | Drug substance, Drug product | 2017-10-16 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-002 | 7855211 | 2031-09-28 | U-2135 | Drug substance, Drug product | 2017-10-16 | 011fe1cb6892… |
| 2026-02-19 14:30 UTC | 2026-02 | N208716-002 | 7855211 | 2031-09-28 | U-3546 | Drug substance, Drug product | 2017-10-16 | 011fe1cb6892… |
| Captured | Edition | Application-product | Exclusivity code | Expiration | Source SHA-256 |
|---|---|---|---|---|---|
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-001 | I-877 | 2024-10-12 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-001 | NPP | 2024-10-12 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-002 | I-877 | 2024-10-12 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-002 | NPP | 2024-10-12 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-003 | I-877 | 2024-10-12 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-003 | NPP | 2024-10-12 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-004 | I-877 | 2024-10-12 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N208716-004 | NPP | 2024-10-12 | 03ed91905a0d… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-001 | I-877 | 2024-10-12 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-001 | NPP | 2024-10-12 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-002 | I-877 | 2024-10-12 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-002 | NPP | 2024-10-12 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-003 | I-877 | 2024-10-12 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-003 | NPP | 2024-10-12 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-004 | I-877 | 2024-10-12 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N208716-004 | NPP | 2024-10-12 | 2680178bc6a6… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-001 | I-877 | 2024-10-12 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-001 | NPP | 2024-10-12 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-002 | I-877 | 2024-10-12 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-002 | NPP | 2024-10-12 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-003 | I-877 | 2024-10-12 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-003 | NPP | 2024-10-12 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-004 | I-877 | 2024-10-12 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N208716-004 | NPP | 2024-10-12 | 5bbf6a4d5a75… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N208716-001 | I-877 | 2024-10-12 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N208716-001 | NPP | 2024-10-12 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N208716-002 | I-877 | 2024-10-12 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N208716-002 | NPP | 2024-10-12 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N208716-003 | I-877 | 2024-10-12 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N208716-003 | NPP | 2024-10-12 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N208716-004 | I-877 | 2024-10-12 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N208716-004 | NPP | 2024-10-12 | d8e5a09893c0… |
| 2024-10-29 15:01 UTC | 2024-10 | N208716-001 | I-877 | 2024-10-12 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N208716-001 | NPP | 2024-10-12 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N208716-002 | I-877 | 2024-10-12 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N208716-002 | NPP | 2024-10-12 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N208716-003 | I-877 | 2024-10-12 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N208716-003 | NPP | 2024-10-12 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N208716-004 | I-877 | 2024-10-12 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N208716-004 | NPP | 2024-10-12 | d06236e962d9… |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| 5b2d0f4e-5bba-4048-a2f0-bcb4b779efc0 | be4bc0de-0fdc-4d46-8d25-be43c79e6a06 | 2026-07-13 | Warnings, Adverse reactions | be4bc0de-0fdc-4d46-8d25-be43c79e6a06 |
Adverse event summaries are temporarily unavailable. Other product information remains available.