IBRANCE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IBRANCE (IBRANCE).
Cyclin-dependent kinase (CDK) 4 and 6 inhibitor; inhibits retinoblastoma protein phosphorylation, blocking cell cycle progression from G1 to S phase.
| Metabolism | Primarily metabolized by CYP3A4; minor contribution from CYP3A5. |
| Excretion | Primarily hepatic metabolism (CYP3A4) with fecal elimination as major route (~81% of dose in feces, 17% in urine as metabolites, <1% unchanged). |
| Half-life | Terminal half-life 26.3–28.1 hours (single dose), steady-state achieved within 8 days, consistent with once-daily dosing. |
| Protein binding | ~85% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Mean Vd/F approximately 2923 L (range 1623–5221 L) indicating extensive tissue distribution, not expressed per kg. |
| Bioavailability | Absolute oral bioavailability ~46% (range 24–68%) under fasting conditions; food increases exposure (AUC 1.84-fold with high-fat meal). |
| Onset of Action | Onset of clinical effect (e.g., neutropenia, tumor response) typically within 1–2 weeks after starting oral administration. |
| Duration of Action | Duration of CDK4/6 inhibition persists for the dosing interval (24 h); continuous dosing required for sustained effect. |
125 mg orally once daily with food for 21 days followed by 7 days off treatment in a 28-day cycle.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment is recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce dose to 75 mg once daily. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 75 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients; no specific dosing guidelines available. |
| Geriatric use | No specific dose adjustment is required for elderly patients; monitor for increased toxicity due to possible age-related renal or hepatic decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IBRANCE (IBRANCE).
| Breastfeeding | No data are available on the presence of palbociclib in human milk, its effects on the breastfed infant, or its effects on milk production. Based on animal studies, palbociclib and its metabolites are excreted into rat milk at concentrations up to 3.7 times maternal plasma. The M/P ratio is not known in humans. Because of the potential for serious adverse reactions in nursing infants, women should not breastfeed during treatment with IBRANCE and for at least 3 weeks after the last dose. |
| Teratogenic Risk | Based on animal studies and its mechanism of action (CDK4/6 inhibition), IBRANCE (palbociclib) is expected to cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, palbociclib was embryo-fetal toxic and teratogenic at maternal exposures below the recommended human dose. It is contraindicated in pregnancy. Fetal risks are present throughout all trimesters, with highest risk during organogenesis (first trimester). |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with strong CYP3A4 inducers"]
| Precautions | ["Neutropenia: monitor complete blood count at baseline and before each cycle; dose interruption/reduction may be required","Interstitial lung disease (ILD)/pneumonitis: monitor for pulmonary symptoms; discontinue if severe","Hepatotoxicity: monitor liver function tests; dose adjustment may be necessary","Embryo-fetal toxicity: can cause fetal harm; advise females of reproductive potential to use effective contraception","QT prolongation: consider ECG monitoring in patients at risk"] |
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| Fetal Monitoring | If IBRANCE is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Pregnancy testing should be performed prior to initiation of therapy. Women of reproductive potential should use effective contraception during treatment and for at least 3 weeks after the last dose. Fetal monitoring should include ultrasound for fetal growth and development, as well as assessment for oligohydramnios and other anomalies. |
| Fertility Effects | Based on animal studies, palbociclib may impair fertility in males and females of reproductive potential. In female rats, palbociclib caused irregular estrous cycles, decreased corpora lutea, and reduced fertility at exposures ≥10 times the human exposure. In male rats, reduced sperm motility and concentration were observed at exposures ≥2 times the human exposure. The reversibility of these effects is unknown. In humans, there are no data on the effect of palbociclib on fertility. |