Abemaciclib

Abemaciclib is typically indicated for the treatment of:

1. Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Advanced Breast Cancer:
• In combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women.
• In combination with fulvestrant in patients who have progressed on endocrine therapy.
2. Metastatic Breast Cancer:
• As a monotherapy in patients who have previously received endocrine therapy and chemotherapy.

• Monotherapy: 200 mg orally twice daily.
• In combination with endocrine therapy (e.g., fulvestrant, aromatase inhibitors): 150 mg orally twice daily.
  Continue treatment until disease progression or unacceptable toxicity.

• May be taken with or without food.
• If a dose is missed or vomited, do not take an extra dose; take the next dose at the regular time.

Mechanism of Action:
Abemaciclib is a selective inhibitor of cyclin-dependent kinases (CDK) 4 and 6. It blocks phosphorylation of the retinoblastoma (Rb) protein, preventing cell cycle progression from G1 to S phase, leading to inhibition of cancer cell proliferation in hormone receptor-positive breast cancer.

Pharmacokinetics:

• Absorption: Median time to peak plasma concentration (Tmax) is ~8 hours after oral administration.
• Bioavailability: Absolute oral bioavailability is ~45%.
• Protein Binding: ~96% bound to plasma proteins.
• Metabolism: Primarily metabolized by CYP3A4 to active metabolites.
• Elimination: Mainly excreted via feces (81%), minimal renal elimination (~3%).
• Half-life: Approx. 18 hours.

Abemaciclib is not recommended during pregnancy, as animal studies have shown it may cause embryo-fetal harm; women of childbearing potential should use effective contraception during treatment and for at least 3 weeks after the last dose. It is unknown whether abemaciclib is excreted in human milk; however, due to the potential for serious adverse effects in breastfed infants, breastfeeding should be avoided during treatment and for at least 3 weeks after the final dose.

Cyclin-Dependent Kinase (CDK) 4/6 Inhibitor (Antineoplastic Agent)

Abemaciclib is primarily metabolized by CYP3A4; thus:

• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) ↑ abemaciclib levels → ↑ risk of toxicity.
• CYP3A4 inducers (e.g., rifampin, phenytoin, St. John’s Wort) ↓ abemaciclib levels → ↓ efficacy.
• May increase plasma levels of sensitive CYP3A4 substrates (e.g., midazolam, theophylline).
• Caution with drugs that increase the risk of QT prolongation or thromboembolism.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F). Keep in a dry place, protected from moisture and heat.