1. Pharmacology

  • Class & Mechanism: Abemaciclib is an orally active, selective cyclin-dependent kinase (CDK) 4 and 6 inhibitor.

  • Action: CDK4/6, when complexed with D-type cyclins, promote cell cycle progression from the G1 to S phase. Abemaciclib inhibits phosphorylation of the retinoblastoma protein (Rb), causing cell cycle arrest at G1, leading to reduced proliferation of breast cancer cells.

  • Pharmacokinetics:

    • Absorption: Oral bioavailability ~45%.

    • Tmax: 8 hours.

    • Metabolism: Extensively metabolized in the liver via CYP3A4.

    • Half-life: ~18 hours.

    • Excretion: Primarily via feces (~81%), urine (~3%).

  1. Dosage & Administration

  • Indication (Adults):

    • HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with endocrine therapy (e.g., aromatase inhibitors, fulvestrant), or as monotherapy after endocrine therapy and chemotherapy failure.

  • Recommended Dose:

    • 150 mg orally twice daily in combination with endocrine therapy.

    • 200 mg orally twice daily as monotherapy.

  • Administration:

    • With or without food.

    • Swallow whole; do not crush/chew.

  • Dose Adjustment:

    • Reduce in case of toxicity, hepatic impairment, or with strong CYP3A inhibitors.

    • Common reduced doses: 100 mg twice daily → 50 mg twice daily if needed.

  1. Drug Interactions

  • CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin, itraconazole): ↑ Abemaciclib exposure → avoid or reduce dose.

  • CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s Wort): ↓ Abemaciclib exposure → avoid coadministration.

  • P-gp and BCRP substrates: Abemaciclib may increase plasma levels of coadministered drugs.

  1. Side Effects
  2. Very Common (≥20%):

  • Diarrhea

  • Neutropenia, leukopenia, anemia

  • Fatigue

  • Nausea, vomiting

  • Decreased appetite

  • Abdominal pain

  • Infections

  • Increased serum creatinine (due to tubular secretion inhibition, not renal dysfunction)

  1. Less Common but Serious:

  • Venous thromboembolism (VTE)

  • Interstitial lung disease (ILD) / pneumonitis

  • Hepatotoxicity (↑ ALT/AST)

  1. Pregnancy & Lactation

  • Pregnancy: Category D – Can cause fetal harm (based on animal studies). Avoid during pregnancy.

  • Contraception: Effective contraception is required during treatment and for at least 3 weeks after the last dose.

  • Lactation: Contraindicated; excretion in human milk is unknown, but risk to infant exists. Breastfeeding should be discontinued.

  1. Precautions & Warnings

  • Monitor complete blood count (CBC) before treatment, every 2 weeks for 2 months, then monthly.

  • Monitor liver function tests (LFTs) regularly.

  • Caution in patients with VTE risk.

  • Withhold or discontinue for severe diarrhea, hepatotoxicity, or neutropenia.

  • Pulmonary symptoms → evaluate for ILD/pneumonitis.

  1. Use in Special Populations

  • Renal Impairment: No adjustment for mild/moderate impairment. Not studied in severe impairment (CrCl <30 mL/min).

  • Hepatic Impairment:

    • Mild/Moderate (Child-Pugh A/B): No adjustment.

    • Severe (Child-Pugh C): Reduce dosing frequency to once daily.

  • Elderly: No dose adjustment needed, but monitor closely.

  1. Therapeutic Class

  • Targeted Cancer Therapy

  • CDK4/6 Inhibitor

  1. Storage Conditions

  2. Store at 20°C to 25°C (room temperature).

  3. Excursions permitted: 15–30°C.

  4. Keep in original container, tightly closed, protected from moisture.

Scroll to Top