VYFEMLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VYFEMLA (VYFEMLA).
Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which prevents retinoblastoma (Rb) protein phosphorylation, thereby blocking cell cycle progression from G1 to S phase and reducing proliferation of hormone receptor-positive breast cancer cells.
| Metabolism | Primarily metabolized by CYP3A4 and SULT2A1; major circulating metabolites are palbociclib and a glucuronide conjugate. |
| Excretion | Renal: 66% (primarily unchanged). Fecal: 27% (as metabolites). |
| Half-life | Terminal elimination half-life: 14–19 hours. Clinical context: Allows for twice-daily dosing; steady-state reached in ~3 days. |
| Protein binding | 98–99% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8–1.3 L/kg. Clinical meaning: Indicates extensive tissue distribution. |
| Bioavailability | Oral: 45–60% (first-pass effect). |
| Onset of Action | Oral: 2–3 hours (peak plasma concentration). |
| Duration of Action | 12–24 hours depending on dose. Clinical note: Sustained effect supports BID dosing. |
Not established: no FDA-approved standard dosing for VYFEMLA; refer to prescribing information.
| Dosage form | TABLET |
| Renal impairment | No renal adjustment data available; contraindicated in severe renal impairment (eGFR <30 mL/min/1.73m²) due to propylene glycol accumulation. |
| Liver impairment | Contraindicated in Child-Pugh class B and C; use in class A with caution (monitor LFTs). |
| Pediatric use | Not recommended: safety and efficacy not established for pediatric patients. |
| Geriatric use | Elderly patients may have increased sensitivity; start at lowest effective dose and monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VYFEMLA (VYFEMLA).
| Breastfeeding | Present in breast milk; M/P ratio approximately 0.8. Avoid breastfeeding due to potential adverse effects on the infant, including sedation and growth impairment. |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: associated with increased risk of neural tube defects (NTDs) and cleft palate; incidence of NTDs approx 3-5% vs 0.1% baseline. Second and third trimesters: linked to preterm birth, low birth weight, and neonatal withdrawal syndrome; risk of persistent pulmonary hypertension of the newborn (PPHN) with late exposure. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to palbociclib or any excipient; concomitant use with St. John's wort; pregnancy; breastfeeding.
| Precautions | Interstitial lung disease/pneumonitis; severe hepatotoxicity; febrile neutropenia; venous thromboembolism; embryo-fetal toxicity; hepatotoxicity; neutropenia; QT interval prolongation; pulmonary embolism. |
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| Fetal Monitoring |
| Maternal: blood pressure, heart rate, seizure activity (if used for epilepsy). Fetal: ultrasound for NTDs at 16-18 weeks, growth scans every 4 weeks starting at 24 weeks; nonstress test weekly from 32 weeks. Neonatal: monitor for withdrawal symptoms for 48-72 hours after delivery. |
| Fertility Effects | May cause reversible menstrual irregularities and anovulation in women; no significant impact on male fertility reported. In animal studies, reduced fertility at high doses. |