Generic
Palbociclib
8 brands available in the market
At a glance
Palbociclib is a CDK4/6 inhibitor used for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. It blocks cell cycle progression from G1 to S phase to reduce cancer cell proliferation.
Description
Palbociclib is a reversible, selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. Cyclin D1, CDK 4 and 6 are downstream of multiple signalling pathways which lead to cellular proliferation. Inhibition of CDK4/6 reduces proliferation of breast cancer cell lines by blocking progression from G1 into S phase of the cell cycle.
Indications
- Hormone receptor-positive, HER2-negative advanced or metastatic breast cancer (with aromatase inhibitor or with fulvestrant after endocrine therapy)
Therapeutic class
Protein Kinase Inhibitor
Pharmacological class
CDK4/6 Inhibitor
Pharmacology
Palbociclib inhibits CDK4 and 6 to block cell cycle progression from G1 to S phase, reducing proliferation of ER-positive breast cancer cells. Combination with antiestrogens decreases RB phosphorylation and E2F expression and increases cell senescence.
Mechanism of action
Prevents cancer cell proliferation by inhibiting CDK4/6.
Dosage
Adult Dose (Oral):
- Recommended dose: 125 mg once daily for 21 days (with food), then 7 days off; repeat every 28 days
- First dose reduction: 100 mg/day
- Second dose reduction: 75 mg/day
- Severe hepatic impairment (Child-Pugh C): 75 mg/day
Administration
- Take with food
- Take at approximately the same time each day
- Swallow capsule whole; do not chew, crush or break
Missed dose
If you miss a dose, skip it and take the next dose at the scheduled time; do not double the dose.
Side effects
Common Side Effects:
- Neutropenia (80-83%)
- Leukopenia
- Fatigue
- Nausea
- Hair loss
- Stomatitis
- Diarrhea
- Anemia
- Rash
- Thrombocytopenia
- Infections
- Decreased appetite
- Fever
Serious: Interstitial Lung Disease/Pneumonitis (1%), Febrile neutropenia (1.8%)
Precautions & warnings
- Monitor neutropenia: CBC before treatment, at start of each cycle and on Day 15
- Withhold if ILD/pneumonitis symptoms occur
- Can cause fetal harm; use effective contraception (up to 3 weeks after last dose)
- Caution while driving (may cause fatigue)
Contraindications
- Pregnancy and lactation
Drug interactions
- Increased exposure with strong CYP3A inhibitors (itraconazole 87% increase); avoid grapefruit
- Decreased exposure with strong CYP3A inducers (rifampin 85% decrease)
- May increase exposure of CYP3A substrates with narrow therapeutic index
Food interactions
Safety with alcohol not known; consult doctor.
Use in pregnancy
Use in Pregnancy: Palbociclib is highly unsafe during pregnancy; definite evidence of severe fetal harm.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Palbociclib is unsafe during breastfeeding; may cause toxicity to the baby.
Pediatric use
Not indicated for children.
Geriatric use
Elderly may require dose adjustment.
Renal / hepatic impairment
Renal Impairment: Safe in kidney disease; no dose adjustment needed (CrCl >15 mL/min).
Hepatic Impairment: Mild-moderate (Child-Pugh A/B): No dose adjustment; Severe (Child-Pugh C): 75 mg/day.
Overdose effects
No specific antidote for overdose; general supportive measures.
Storage conditions
Store below 30°C; protect from light & moisture; keep out of reach of children.
Chemical structure
Palbociclib