- 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.