Abemaciclib

FDA Drug Information • Also known as: Verzenio

Brand Names: Verzenio
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION Abemaciclib is a kinase inhibitor for oral administration. It is a white to yellow powder with the empirical formula C 27 H 32 F 2 N 8 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)-1 H -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 Structure

What Is Abemaciclib Used For?

1 INDICATIONS AND USAGE VERZENIO ® is a kinase inhibitor indicated: in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence. ( 1.1 , 14.1 ) in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. ( 1.2 ) in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. ( 1.2 ) as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. ( 1.2 ) 1.1 Early Breast Cancer VERZENIO ® (abemaciclib) is indicated: in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence [see Clinical Studies ( 14.1 )]. 1.2 Advanced or Metastatic Breast Cancer VERZENIO (abemaciclib) is indicated: in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION VERZENIO tablets are taken orally with or without food. ( 2.1 ) Recommended starting dose in combination with fulvestrant, tamoxifen, or an aromatase inhibitor: 150 mg twice daily. ( 2.1 ) Recommended starting dose as monotherapy: 200 mg twice daily. ( 2.1 ) Dosing interruption and/or dose reductions may be required based on individual safety and tolerability. ( 2.2 ) 2.1 Recommended Dose and Schedule When used in combination with fulvestrant, tamoxifen, or an aromatase inhibitor, the recommended dose of VERZENIO is 150 mg taken orally twice daily. Refer to the Full Prescribing Information for the recommended dose of the fulvestrant, tamoxifen, or aromatase inhibitor being used. Pre/perimenopausal women and men treated with the combination of VERZENIO plus an aromatase inhibitor should be treated with a gonadotropin-releasing hormone agonist (GnRH) according to current clinical practice standards. Pre/perimenopausal women treated with the combination of VERZENIO plus fulvestrant should be treated with a GnRH according to current clinical practice standards When used as monotherapy, the recommended dose of VERZENIO is 200 mg taken orally twice daily. For early breast cancer, continue VERZENIO until completion of 2 years of treatment or until disease recurrence, or unacceptable toxicity. For advanced or metastatic breast cancer, continue treatment until disease progression or unacceptable toxicity. VERZENIO may be taken with or without food [see Clinical Pharmacology ( 12.3 )] . Instruct patients to take their doses of VERZENIO at approximately the same times every day. If the patient vomits or misses a dose of VERZENIO, instruct the patient to take the next dose at its scheduled time. Instruct patients to swallow VERZENIO tablets whole and not to chew, crush, or split tablets before swallowing. Instruct patients not to ingest VERZENIO tablets if broken, cracked, or otherwise not intact. 2.2 Dose Modification Dose Modifications for Adverse Reactions The recommended VERZENIO dose modifications for adverse reactions are provided in Tables 1 - 7 . Discontinue VERZENIO for patients unable to tolerate 50 mg twice daily. Table 1: VERZENIO Dose Modification — Adverse Reactions Dose Level VERZENIO Dose Combination with Fulvestrant, Tamoxifen, or an Aromatase Inhibitor VERZENIO Dose for Monotherapy Recommended starting dose 150 mg twice daily 200 mg twice daily First dose reduction 100 mg twice daily 150 mg twice daily Second dose reduction 50 mg twice daily 100 mg twice daily Third dose reduction not applicable 50 mg twice daily Table 2: VERZENIO Dose Modification and Management — Hematologic Toxicities a Abbreviation: CTCAE = Common Terminology Criteria for Adverse Events. a If blood cell growth factors are required, suspend VERZENIO dose for at least 48 hours after the last dose of blood cell growth factor and until toxicity resolves to ≤Grade 2. Resume at next lower dose unless already performed for the toxicity that led to...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Diarrhea [see Warnings and Precautions ( 5.1 )] . Neutropenia [see Warnings and Precautions ( 5.2 )] . Interstitial Lung Disease (ILD) or Pneumonitis [see Warnings and Precautions ( 5.3 )] . Hepatotoxicity [see Warnings and Precautions ( 5.4 )] . Venous Thromboembolism [see Warnings and Precautions ( 5.5 )] . Most common adverse reactions (incidence ≥20%) were diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety population described in the Warnings and Precautions reflect exposure to VERZENIO in 3691 patients from four clinical trials: monarchE, MONARCH 1, MONARCH 2, and MONARCH 3. The safety population includes exposure to VERZENIO as a single agent at 200 mg twice daily in 132 patients in MONARCH 1 and to VERZENIO at 150 mg twice daily in 3559 patients administered in combination with fulvestrant, tamoxifen, or an aromatase inhibitor in monarchE, MONARCH 2, and MONARCH 3. The median duration of exposure ranged from 4.5 months in MONARCH 1 to 24 months in monarchE. The most common adverse reactions (incidence ≥20%) across clinical trials were: diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia. Early Breast Cancer monarchE: VERZENIO in Combination with Tamoxifen or an Aromatase Inhibitor as Adjuvant Treatment Adult patients with HR-positive, HER2-negative, node-positive early breast cancer at a high risk of recurrence The safety of VERZENIO was evaluated in monarchE, a study of 5591 adult patients receiving VERZENIO plus endocrine therapy (tamoxifen or an aromatase inhibitor) or endocrine therapy (tamoxifen or an aromatase inhibitor) alone [see Clinical Studies ( 14.1 )]. Patients were randomly assigned to receive 150 mg of VERZENIO orally, twice daily, plus tamoxifen or an aromatase inhibitor, or tamoxifen or an aromatase inhibitor, for two years or until discontinuation criteria were met. The median duration of VERZENIO treatment was 24 months. The most frequently reported (≥5%) Grade 3 or 4 adverse reactions were neutropenia, leukopenia, diarrhea, and lymphopenia. Fatal adverse reactions occurred in 0.8% of patients who received VERZENIO plus endocrine therapy (tamoxifen or an aromatase inhibitor), including: cardiac failure (0.1%), cardiac arrest, myocardial infarction, ventricular fibrillation, cerebral hemorrhage, cerebrovascular accident, pneumonitis, hypoxia, diarrhea, and mesenteric artery thrombosis (0.03% each). Permanent VERZENIO treatment discontinuation due to an adverse reaction was reported in 19% of patients receiving VERZENIO, plus tamoxifen or an aromatase inhibitor. Of the patients receiving tamoxifen or an aromatase inhibitor, 1% permanently discontinued due to an adverse reaction. The most common adverse reactions leading to VERZENIO discontinuations were diarrhea (5%), fatigue (2%), and neutropenia (0.9%). Dose interruption of VERZENIO due to an adverse reaction occurred in 62% of patients receiving VERZENIO plus tamoxifen or aromatase inhibitors. Adverse reactions leading to VERZENIO dose interruptions in ≥5% of patients were diarrhea (20%), neutropenia (16%), leukopenia (7%), and fatigue (5%). Dose reductions of VERZENIO due to an adverse reaction occurred in 44% of patients receiving VERZENIO plus endocrine therapy...

Drug Interactions

7 DRUG INTERACTIONS CYP3A Inhibitors: Avoid concomitant use of ketoconazole. Reduce the VERZENIO dose with concomitant use of other strong and moderate CYP3A inhibitors. ( 2.2 , 7.1 ) CYP3A Inducers: Avoid concomitant use of strong and moderate CYP3A inducers. ( 7.1 ) 7.1 Effect of Other Drugs on VERZENIO 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 )] .

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied VERZENIO 50 mg tablets are oval beige tablet with “Lilly” debossed on one side and “50” on the other side. VERZENIO 100 mg tablet are oval white to practically white tablet with “Lilly” debossed on one side and “100” on the other side. VERZENIO 150 mg tablets are oval yellow tablet with “Lilly” debossed on one side and “150” on the other side. VERZENIO 200 mg tablets are oval beige tablet with “Lilly” debossed on one side and “200” on the other side. VERZENIO tablets are supplied in 7-day dose pack configurations as follows: 200 mg dose pack (14 tablets) – each blister pack contains 14 tablets (200 mg per tablet) (200 mg twice daily) NDC 0002-6216-54 150 mg dose pack (14 tablets) – each blister pack contains 14 tablets (150 mg per tablet) (150 mg twice daily) NDC 0002-5337-54 100 mg dose pack (14 tablets) – each blister pack contains 14 tablets (100 mg per tablet) (100 mg twice daily) NDC 0002-4815-54 50 mg dose pack (14 tablets) – each blister pack contains 14 tablets (50 mg per tablet) (50 mg twice daily) NDC 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). How Supplied VERZENIO 50 mg tablets are oval beige tablet with “Lilly” debossed on one side and “50” on the other side. VERZENIO 100 mg tablet are oval white to practically white tablet with “Lilly” debossed on one side and “100” on the other side. VERZENIO 150 mg tablets are oval yellow tablet with “Lilly” debossed on one side and “150” on the other side. VERZENIO 200 mg tablets are oval beige tablet with “Lilly” debossed on one side and “200” on the other side. VERZENIO tablets are supplied in 7-day dose pack configurations as follows: 200 mg dose pack (14 tablets) – each blister pack contains 14 tablets (200 mg per tablet) (200 mg twice daily) NDC 0002-6216-54 150 mg dose pack (14 tablets) – each blister pack contains 14 tablets (150 mg per tablet) (150 mg twice daily) NDC...

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.