II. Indications
- Hormone Receptor positive, HER2 Negative advanced or metastatic Breast Cancer
III. Contraindications
-
QT Prolongation (Ribociclib)
- Also correct Electrolyte abnormalities (e.g. Magnesium, Potassium) before use
- Avoid with other Medication Causes of QTc Prolongation
IV. Mechanism
- Cyclin-Dependent Kinase
- CDK4 (Cyclin D1) and CDK6 (Cyclin D3) are Serine-Threonine kinases
- These kinases become unregulated in some tumor types (e.g. Retinoblastoma), resulting in tumor cell growth
- Cyclin-Dependent Kinase 4 and 6 Inhibitor (CDK 4 and 6)
- Selective inhibition of cyclin-dependent kinase CDK4 and CDK6
- Inhibit Retinoblastoma (Rb) Protein phosphorylation during early G1-S Phase and results in cell cycle arrest
V. Medications
- Palbociclib (Ibrance)
- Risks include Neutropenia, Venous Thromboembolism
- Avoid with strong CYP3A Inhibitors, strong CYP3A Inducers and narrow therapeutic range CYP3A Substrates
- Ribociclib (Kisquali)
- Risks include Neutropenia, QT Prolongation, hepatotoxicity
- Avoid with strong CYP3A Inhibitors, strong CYP3A Inducers and narrow therapeutic range CYP3A Substrates
- Abemaciclib (Verzenio)
- Risk of severe Diarrhea, Neutropenia, hepatotoxicity, Venous Thromboembolism
- Avoid with strong CYP3A Inhibitors and strong CYP3A Inducers
VI. Dosing
- See other references for disease specific dosing protocols
VII. Adverse Effects
- Neutropenia (all CDK Inhibitors)
- Venous Thromboembolism (Palbociclib, Abemaciclib)
- Hepatotoxicity (Ribociclib, Abemaciclib)
- QT Prolongation (Ribociclib)
- Severe Diarrhea (Abemaciclib)
VIII. Safety
- Avoid in Lactation
- Avoid in pregnancy (all trimesters, pregnancy category X)
- Use reliable Contraception including for at least 2 weeks after last dose
- Men should use reliable Contraception for at least 3 months after last dose of Palbociclib
- Monitoring
- Complete Blood Count
- Obtain baseline, and per cycle regimen
- Electrocardiogram (Ribociclib)
- Liver Function Tests (Ribociclib, Abemaciclib)
- Complete Blood Count
IX. Drug Interactions
- Strong CYP3A Inhibitors, strong CYP3A Inducers and narrow therapeutic range CYP3A Substrates
- Avoid with Palbociclib, Ribociclib, Abemaciclib
-
Medication Causes of QTc Prolongation
- Avoid with Ribociclib
X. Resources
- Palbociclib (DailyMed)
- Ribociclib (DailyMed)
- Abemaciclib (DailyMed)