Ibrance®Palbociclib Capsules

1. Indications and Usage
HR-Positive, HER2-Negative Breast Cancer: Treatment of postmenopausal women and men with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer .
Clinical Stages:
First-line: In combination with an aromatase inhibitor (e.g., letrozole) as initial endocrine-based therapy .
Second-line/Subsequent: In combination with fulvestrant in patients with disease progression following endocrine therapy .
2. Dosage and Administration
Administration: Oral administration. Capsules must be swallowed whole (do not chew, crush, or open).
Food Requirement: Must be taken with food (ideally at the same time each day) to ensure consistent absorption and minimize gastrointestinal side effects .
Standard Dose:
Recommended Dose: 125 mg once daily.
Cycle: Take daily for 21 consecutive days, followed by a 7-day rest period (a 28-day cycle) .
Missed Dose/Vomiting: If a dose is missed or if vomiting occurs, do not re-administer the dose. Resume at the usual time for the next scheduled dose .
Dose Adjustment: Mandatory dose reduction (to 100 mg, then 75 mg) for severe neutropenia (Grade 4), febrile neutropenia, or other severe non-hematologic toxicities .
3. Mechanism of Action
Palbociclib is a potent, selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6).
In HR-positive breast cancer, estrogen receptor signaling drives proliferation by upregulating cyclin D1, which binds to CDK4/6 to promote cell cycle progression from G1 to S phase.
By inhibiting CDK4/6, palbociclib prevents retinoblastoma protein (Rb) phosphorylation, leading to cell cycle arrest and inhibition of tumor cell proliferation .
4. Safety and Warnings
Neutropenia: Severe neutropenia is the most common serious adverse reaction. Monitor Complete Blood Counts (CBC) before each cycle and during the first two cycles .
Pulmonary Embolism (PE): Cases of PE have been reported. Monitor for signs of PE (e.g., shortness of breath, chest pain) and interrupt treatment if suspected .
Embryo-Fetal Toxicity: May cause fetal harm. Contraception is required for females of reproductive potential and males with female partners of reproductive potential .
Diarrhea: Can cause diarrhea; monitor and manage symptoms early .
5. Adverse Reactions
Common adverse reactions (incidence ≥20%) include:
Neutropenia, Leukopenia, Anemia.
Fatigue, Asthenia.
Nausea, Diarrhea, Vomiting, Stomatitis.
Alopecia (Hair loss), Headache.
Infections (e.g., upper respiratory infections) .
6. Drug Interactions
CYP3A Substrate:
Inhibitors: Avoid strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, grapefruit juice) as they significantly increase Palbociclib exposure. If unavoidable, reduce dose to 75 mg .
Inducers: Avoid strong CYP3A inducers (e.g., rifampin, carbamazepine, St. John’s wort) as they reduce efficacy .
7. Pharmaceutical Information
Chemical Name: 6-acetyl-2-(4-(2-pyrrolidin-1-yl-ethoxy)phenyl)-8-methyl-2H-pyrazolo