PALBOCICLIB CAPSULES
Clinical safety rating: avoid
Strong CYP3A4 inhibitors may increase levels Can cause severe neutropenia and pulmonary embolism.
Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), preventing phosphorylation of retinoblastoma protein, thereby blocking cell cycle progression from G1 to S phase.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP3A5. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and SULT2A1, with 74.1% of dose recovered in feces (56.5% as unchanged drug, 17.6% as metabolites) and 17.5% in urine (1.2% unchanged). Minor biliary excretion contributes to fecal elimination. |
| Half-life | Mean terminal half-life is 29 hours (range 26–38 hours) at steady state, supporting once-daily dosing. |
| Protein binding | Approximately 85% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Mean apparent volume of distribution (Vz/F) is 2584 L (approximately 34 L/kg for a 75 kg patient), indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is approximately 46% (range 30–60%), with a high-fat meal increasing AUC by 21% and Cmax by 12% relative to fasting. |
| Onset of Action | Onset of cell cycle arrest occurs within hours of first dose; clinical response (tumor reduction) typically observed after 2–4 weeks of continuous dosing. |
| Duration of Action | Duration of CDK4/6 inhibition persists for the dosing interval (24 hours); clinical effect sustained with daily administration, with recovery of neutrophil counts during 7-day break in 3/1 schedule. |
125 mg orally once daily for 21 days followed by 7 days off treatment, 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 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 75 mg once daily. Child-Pugh C: avoid use. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required. Clinical studies included patients ≥65 years; no overall differences in safety or efficacy observed. |
| 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.
| FDA category | Contraindicated |
| Breastfeeding | No data on the presence of palbociclib in human milk, effects on the breastfed infant, or effects on milk production. Palbociclib and its metabolites are present in rat milk at concentrations higher than maternal plasma. Because of the potential for serious adverse reactions in breastfeeding infants, advise women not to breastfeed during treatment and for at least 3 weeks after the last dose. M/P ratio: not available in humans. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA boxed warning exists for palbociclib.
| Common Effects | Myelosuppression |
| Serious Effects |
["Hypersensitivity to palbociclib or any component of the formulation","Concomitant use with strong CYP3A4 inducers (avoid)"]
| Precautions | ["Neutropenia: Monitor complete blood count prior to start and at the beginning of each cycle, and as clinically indicated. Dose interruption, reduction, or delay may be required.","Interstitial lung disease (ILD)/pneumonitis: Monitor for pulmonary symptoms; discontinue if severe.","Hepatobiliary toxicity: Monitor liver function tests.","Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk and use effective contraception."] |
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| PALBOCICLIB is contraindicated during pregnancy. Based on its mechanism of action (CDK4/6 inhibition) and animal studies, palbociclib is expected to cause fetal harm. In animal reproduction studies, palbociclib was embryotoxic and teratogenic at maternal exposures below the clinical exposure at the recommended human dose. First trimester: high risk of structural abnormalities. Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and fetal demise. Women of reproductive potential should use effective contraception during treatment and for at least 3 weeks after the last dose. |
| Fetal Monitoring | Pregnancy test prior to initiation of therapy in women of reproductive potential. If pregnancy occurs, palbociclib should be discontinued, and the patient should be apprised of the potential hazard to the fetus. Fetal monitoring should include serial ultrasound assessments for growth, amniotic fluid volume, and fetal anatomy. Neonatal monitoring for signs of toxicity (e.g., myelosuppression, infection) is recommended. |
| Fertility Effects | Based on animal studies, palbociclib may impair male and female fertility. In female rats, palbociclib caused decreased fertility, corpora lutea, and implantation sites, and increased pre- and post-implantation loss. In male rats, palbociclib caused decreased sperm motility and count, and testicular degeneration at clinically relevant exposures. These effects were partially reversible. Human data are lacking. Advise patients of potential impact on fertility. |