Verzenio

— THERAPEUTIC CATEGORIES —
  • Breast cancer
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Verzenio Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Abemaciclib 50mg, 100mg, 150mg, 200mg; tabs.

    Pharmacological Class

    Kinase inhibitor.

    How Supplied

    Tabs—14 (blister pack)

    Manufacturer

    Eli Lilly and Company

    Generic Availability

    NO

    Mechanism of Action

    Abemaciclib is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). In estrogen receptor-positive 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.

    Verzenio Indications

    Indications

    In combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adults with HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence. In combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer. In combination with fulvestrant for treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. As monotherapy for adults with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

    Verzenio Dosage and Administration

    Adult

    Swallow whole. Take at the same time every day. In combination with fulvestrant, tamoxifen, or an aromatase inhibitor (see full labeling): 150mg twice daily; in pre/perimenopausal women and men (in combination with aromatase inhibitor) or in pre/perimenopausal women (in combination with fulvestrant): also treat with a gonadotropin-releasing hormone agonist according to current practice standards. Monotherapy: 200mg twice daily. Early breast cancer: continue until completion of 2yrs of treatment or until disease recurrence, or unacceptable toxicity. Advanced or metastatic breast cancer: continue until disease progression or unacceptable toxicity. Dose modifications for adverse reactions, concomitant strong CYP3A4 inhibitors: see full labeling. Severe hepatic impairment: reduce frequency to once daily.

    Children

    Not established.

    Verzenio Contraindications

    Not Applicable

    Verzenio Boxed Warnings

    Not Applicable

    Verzenio Warnings/Precautions

    Warnings/Precautions

    Advise patients to initiate antidiarrheal (eg, loperamide) and increase fluids at first sign of loose stools; discontinue if Grade 3/4 diarrhea occurs or hospitalization required, until resolves to ≤Grade 1, then resume at next lower dose. Monitor CBCs and LFTs prior to initiation, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Monitor for interstitial lung disease (ILD)/pneumonitis. Dose interruption/reduction/discontinuation or delay in starting treatment cycles if Grade 3/4 neutropenia, persistent/recurrent Grade 2 or Grade 3/4 transaminase elevation or ILD/pneumonitis occurs. Monitor for venous thromboembolic events (VTE); treat appropriately. Dose interruption for early breast cancer patients with any grade VTE or for advanced or metastatic breast cancer patients with a Grade 3/4 VTE. Severe hepatic impairment (Child-Pugh C): see Adult. Severe renal impairment (CrCl <30mL/min), ESRD, or on dialysis. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during therapy and for ≥3 weeks after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for ≥3 weeks after the last dose).

    Verzenio Pharmacokinetics

    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).

    A high-fat, high-calorie meal (~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

    Human plasma protein bound: 96.3%. Geometric mean systemic volume of distribution: ~690.3 L (49% CV).

    Metabolism

    Hepatic (CYP3A4). 

    Elimination

    Fecal (~81%), renal (~3%). Half-life: 18.3 hours. Geometric mean hepatic clearance: 26.0 L/h (51% CV).

    Verzenio Interactions

    Interactions

    Avoid concomitant ketoconazole, grapefruit products. Concomitant other strong CYP3A inhibitors: reduce abemaciclib dose; moderate inhibitors: monitor and consider reducing dose. Avoid concomitant strong or moderate CYP3A inducers (eg, rifampin): consider alternative agents.

    Verzenio Adverse Reactions

    Adverse Reactions

    Diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, thrombocytopenia; venous thrombosis, pulmonary embolism, ILD/pneumonitis, hepatotoxicity.

    Verzenio Clinical Trials

    See Literature

    Verzenio Note

    Not Applicable

    Verzenio Patient Counseling

    See Literature

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