Ibrance
Ibrance
Generic Name
Ibrance
Mechanism
- CDK4/6 inhibition → blocks phosphorylation of the retinoblastoma protein (Rb)
- Arrests cell cycle in the G1 phase, preventing transition to S phase and thus inhibiting tumor proliferation
- Selective for CDK4/6 → preserves many CDK1, CDK2, and CDK5 functions, reducing off‑target toxicity
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Pharmacokinetics
| Feature | Details |
| Absorption | Oral; ~70 % bioavailability; peak plasma 6 h post‑dose |
| Distribution | 90 % protein‑bound (primarily α‑1‑acid glycoprotein) |
| Metabolism | Primarily CYP3A4/5; minor CYP2D6 contribution |
| Elimination | ~75 % fecal, ~20 % renal; half‑life ~29 h (continuous dose) |
| Drug–Drug Interaction | Potentiated by strong CYP3A4 inhibitors (ketoconazole, clarithromycin); reduced by CYP3A4 inducers (rifampin, carbamazepine) |
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Indications
- Hormone‑receptor positive (ER⁺/PR⁺), HER2‑negative advanced/metastatic breast cancer
- First‑line: *palbociclib* + endocrine therapy (e.g., aromatase inhibitor or fulvestrant)
- Second‑line: *palbociclib* + fulvestrant after endocrine resistance
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Contraindications
- Contraindications: Severe hepatic impairment (Child‑Pugh C); concomitant strong CYP3A4 inhibitors cannot be avoided; known hypersensitivity to palbociclib.
- Warnings:
- Myelosuppression → neutropenia, thrombocytopenia, anemia
- QT prolongation (rare) – avoid with co‑administration of QT‑prolonging agents
- Pregnancy: Category D – teratogenic in animal studies; avoid in pregnancy; require effective contraception.
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Dosing
- Standard dose: 125 mg orally once daily, 3 weeks on/1 week off (28‑day cycle)
- Paclitaxel‑based (dose‑adjusted): 120 mg/m² orally once daily, 3 weeks on/1 week off
- Administration: With or without food; ensure meal consistency to maintain absorption.
- Dose‑reduction:
- Hematologic: reduce to 100 mg or 90 mg × 3 weeks/1 week if grade ≥ 3 neutropenia or thrombocytopenia
- Non‑hematologic: if persistent grade ≥ 3 toxicity, consider hold/stop.
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Adverse Effects
| Grade ≥ 3 | Frequency (≥ 10 %) | Comments |
| Neutropenia | ~42 % | Usually transient; monitor CBC 3–4 weeks into cycle |
| Anemia | ~12 % | Manage with supportive care; consider RBC transfusion if symptomatic |
| Thrombocytopenia | ~9 % | Platelet counts 10× ULN)
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Monitoring
| Parameter | Timing | Target |
| CBC (neutrophils, platelets, hemoglobin) | Baseline; every 2 weeks first cycle, then monthly | Neutrophils > 1.5 × 10⁹/L, platelets > 75 k/µL |
| Liver function tests (ALT/AST, bilirubin) | Baseline; every 4 weeks | ALT/AST ≤ 3× ULN |
| EKG | Baseline; if QT‑prolonging drugs added | QTc < 450 ms |
| Pregnancy test | Baseline; monthly if female of reproductive potential | Negative |
| Patient‑reported symptoms | At each visit | Early detection of fatigue, diarrhea, infections |
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Clinical Pearls
1. Cycle‑length flexibility – The 3‑week on/1‑week off schedule improves tolerability; a 2‑week on/2‑week off regimen can be considered for patients with persistent neutropenia.
2. Concurrent chemotherapy – Palbociclib can be safely combined with taxanes; dose adjustment (120 mg/m²) is required to mitigate cumulative myelosuppression.
3. Drug interaction vigilance – Use a pharmacy‑managed list of CYP3A4 inhibitors/inducers; adjust palbociclib dose or avoid concomitant drugs when possible.
4. Patient education – Emphasize adherence to the on/off schedule; missing ≥ 2 days can accelerate resistance.
5. Immunosuppression strategy – For febrile neutropenia, hold one dose and consider empiric broad‑spectrum antibiotics; resume once neutrophils recover.
6. Re‑initiation post‑side‑effect – After resolution of grade ≥ 3 toxicity, restart at 90 mg for 3 weeks, then titrate upward if tolerated.
7. Cardiac monitoring – Even though QT prolongation is rare, baseline EKG is mandatory for patients on concomitant QT‑prolonging agents (e.g., methadone).
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• Key Takeaway: *Palbociclib (Ibrance) is a first‑line, oral CDK4/6 inhibitor that significantly extends progression‑free survival in ER⁺/HER2‑negative metastatic breast cancer when combined with endocrine therapy. Its safety profile hinges on diligent hematologic monitoring and vigilant drug‑interaction management.*