Ribociclib

• Class: CDK4/6 inhibitor (Cyclin-dependent kinase 4 and 6 inhibitor)
• Mechanism of Action:
  
  Ribociclib selectively inhibits CDK4 and CDK6, which are critical for cell cycle progression from G1 to S phase by phosphorylating the retinoblastoma (Rb) protein. Inhibition leads to cell cycle arrest and decreased tumor cell proliferation, especially in hormone receptor–positive (HR+), HER2-negative breast cancer.

Indications

• HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with:
  • Aromatase inhibitors (e.g., letrozole) as initial endocrine-based therapy in postmenopausal women.
  • Fulvestrant in women with disease progression following endocrine therapy.

Dosage

• Standard dose: 600 mg orally once daily for 21 consecutive days followed by 7 days off (28-day cycle).
• Dose adjustments may be required for toxicities or hepatic impairment.

Pharmacokinetics

• Absorption: Oral, peak plasma concentration ~1-4 hours.
• Metabolism: Mainly hepatic via CYP3A4.
• Elimination: Primarily fecal; half-life ~32 hours.

Key Toxicities and Monitoring

• Hematologic: Neutropenia (most common), leukopenia, anemia.
• Non-hematologic: QT prolongation, hepatotoxicity (transaminase elevation), fatigue, nausea.
• Monitoring:
  • CBC at baseline and periodically for neutropenia.
  • Liver function tests at baseline and periodically.
  • ECG at baseline and during treatment to monitor QT interval.
  • Electrolytes (K+, Mg2+, Ca2+) to minimize risk of QT prolongation.

Drug Interactions

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) can increase ribociclib levels — avoid or reduce dose.
• CYP3A4 inducers can reduce efficacy.
• Caution with other QT-prolonging drugs.