PALBOCICLIB

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Cyclin-dependent kinase (CDK) 4 and 6 inhibitor; blocks phosphorylation of retinoblastoma protein, preventing cell cycle progression from G1 to S phase.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and SULT2A1; major route is oxidation and sulfonation.
Excretion	Primarily hepatic metabolism (CYP3A4) with 74% fecal excretion (17% as unchanged drug) and 18% renal excretion (1.5% unchanged).
Half-life	Terminal elimination half-life of 24-29 hours, supporting once-daily dosing; steady-state reached within 8 days.
Protein binding	85% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Approximately 25 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral bioavailability 46% (range 34-67%) with no significant food effect.
Onset of Action	Clinical effect (neutrophil count reduction) observed within 8 days of continuous dosing.
Duration of Action	Myelosuppression persists for 7-10 days after last dose, requiring monitoring and dose adjustments.

Classification & Brands

Dosing & administration

125 mg orally once daily for 21 days, followed by 7 days off treatment; taken with food in combination with an aromatase inhibitor or fulvestrant.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl 30-89 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce dose to 75 mg once daily; not recommended if CrCl <15 mL/min or on dialysis.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce to 75 mg once daily. Child-Pugh C: not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients; no recommended dose.
Geriatric use	No specific dose adjustment required based on age alone; monitor for toxicity due to potential age-related renal or hepatic impairment.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP3A4 inhibitors may increase levels Can cause severe neutropenia and pulmonary embolism.

Breastfeeding	Unknown if palbociclib is excreted in human milk. Plasma protein binding is ~85%, suggesting limited transfer. M/P ratio not established. Due to potential for severe adverse reactions in nursing infants, discontinue breastfeeding during treatment and for at least 3 weeks after the last dose.
Teratogenic Risk	PALBOCICLIB is embryotoxic and fetotoxic in animal studies. Based on its mechanism of action (CDK4/6 inhibition), there is a potential risk of fetal harm. First trimester exposure may increase risk of spontaneous abortion and congenital anomalies; second and third trimester exposure may cause fetal growth restriction and oligohydramnios. Use is contraindicated in pregnancy.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

["Concomitant use with strong CYP3A inhibitors (e.g., ketoconazole) due to increased risk of toxicity","Hypersensitivity to palbociclib or any component of the formulation"]

Clinical Precautions

Precautions

["Interstitial lung disease (ILD)/pneumonitis","Neutropenia; monitor complete blood count before and during therapy","Hepatotoxicity; monitor liver function tests","QT prolongation; avoid in patients with significant baseline QT prolongation or in combination with QT-prolonging drugs","Embryo-fetal toxicity; advise pregnant women of risk","Arterial thromboembolic events","Venous thromboembolism"]

Clinical Tips & Counseling

Drug interactions

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