Abemaciclib

VERZENIO ® is a kinase inhibitor 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. 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 the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. in combination with imlunestrant for the treatment of adults with estrogen receptor (ER)-positive, HER2-negative, estrogen receptor-1 (ESR1) -mutated advanced or metastatic breast cancer, as detected by an FDA-authorized…

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.

Recommended dosage in combination with fulvestrant, tamoxifen, imlunestrant, or an aromatase inhibitor: 150 mg orally twice daily with or without food. Recommended dosage as monotherapy: 200 mg orally twice daily with or without food. See Full Prescribing Information for dosage modifications due to adverse reactions. Severe Hepatic Impairment: Reduce dosage frequency to once daily.

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Diarrhea: VERZENIO can cause severe cases of diarrhea, associated with dehydration and infection. Instruct patients at the first sign of loose stools to initiate antidiarrheal therapy, increase oral fluids, and notify their healthcare provider. Neutropenia: 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. Interstitial Lung Disease (ILD)/Pneumonitis: Severe and fatal cases of ILD/pneumonitis have been reported. Monitor for clinical symptoms or radiological changes indicative of ILD/pneumonitis. Permanently discontinue VERZENIO in all patients with Grade 3 or 4 ILD or pneumonitis. Hepatotoxicity: Increases in serum transaminase levels have been observed. Perform liver function tests (LFTs) before initiating treatment with VERZENIO.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Diarrhea. Neutropenia. Interstitial Lung Disease (ILD) or Pneumonitis. Hepatotoxicity. Venous Thromboembolism. Most common adverse reactions (incidence ≥20%) were diarrhea, infections, neutropenia, fatigue, abdominal pain, nausea, leukopenia, anemia, and vomiting.

CYP3A Inhibitors: Avoid concomitant use of ketoconazole. Reduce the VERZENIO dose with concomitant use of other strong and moderate CYP3A inhibitors. CYP3A Inducers: Avoid concomitant use of strong and moderate CYP3A inducers.

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).