Dosing and uses of Ibrance (palbociclib)
Adult dosage forms and strengths
capsule
- 75mg
- 100mg
- 125mg
Breast Cancer
Indicated for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer
As initial endocrine-based therapy in combination with letrozole
- Indicated as initial endocrine based therapy in postmenopausal women
- Starting dose: 125 mg PO qDay with food x21 days followed by 7 days off therapy to comprise a complete cycle of 28 days
- Given with letrozole 2.5 mg PO qDay continuously throughout the 28-day cycle
Disease progression following endocrine therapy in combination with fulvestrant
- Indicated in combination with fulvestrant in women regardless of menopausal status with disease progression following endocrine therapy
- Starting dose: 125 mg PO qDay with food x21 days followed by 7 days off therapy to comprise a complete cycle of 28 days
- Given with fulvestrant 500 mg IM on days 1, 15, 29, and once monthly thereafter
Dosage modifications
Dose reduction for adverse reaction
- First dose reduction: Reduce to 100 mg/day
- Second dose reduction: Reduce to 75 mg/day
- If further dose reduction below 75 mg/day is required, discontinue the treatment
Hematologic toxicities
- Grade 1 or 2: No dose adjustment required
- Grade 3*:
- Day 1 of cycle: Withhold dose, repeat complete blood count monitoring within 1 week; when recovered to grade ≤2, start the next cycle at the same dose
- Day 14 of first 2 cycles: Continue at current dose to complete cycle; repeat complete blood count on Day 21
- Consider dose reduction in cases of prolonged (>1 week) recovery from grade 3 neutropenia or recurrent grade 3 neutropenia in subsequent cycles
- Grade 3 ANC (<1000 to 500/mm³) + fever ≥38.5ºC and/or infection: Withhold drug until recovery to grade ≤2 (≥1000/mm³); resume at next lower dose
- Grade 4*: Withhold drug until recovery to grade ≤2; resume at next lower dose
- *Except lymphopenia, unless associated with clinical event (eg, opportunistic infections)
Nonhematologic toxicities
- Grade 1 or 2: No dose adjustment required
- Grade ≥3 (if persisting despite medical treatment): Withhold until symptoms resolve to grade ≤1 or grade ≤2 (if not considered a safety risk for patient to resume); resume at next lower dose
Coadministration with strong CYP3A inhibitors
- Avoid concomitant use of strong CYP3A inhibitors and consider an alternative concomitant medication with no or minimal CYP3A inhibition
- If patients must be coadministered a strong CYP3A inhibitor, reduce palbociclib dose to 75 mg/day
- If the strong inhibitor is discontinued, increase the palbociclib dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor
Dosing Considerations
Indication for initial treatment with letrozole in postmenopausal women is approved under accelerated approval based on progression-free survival; continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory triaL
Monitor CBC count at baseline and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated
Pediatric dosage forms and strengths
Not indicated
Ibrance (palbociclib) adverse (side) effects
>10%
Neutropenia, all grades (75%)
Neutropenia, grade 3 (48%)
Leukopenia, all grades (43%)
Fatigue, all grades (41%)
Anemia, all grades (35%)
Upper respiratory tract infection, all grades (31%)
Stomatitis, all grades (25%)
Nausea, all grades (25%)
Alopecia, grade 1 (22%)
Diarrhea, all grades (21%)
Leukopenia, grade 3 (19%)
Thrombocytopenia, all grades (17%)
Decreased appetite, all grades (16%)
Vomiting, all grades (15%)
Peripheral neuropathy, all grades (13%)
Asthenia, all grades (13%)
Epistaxis, all grades (11%)
1-10%
Neutropenia, grade 4 (6%)
Anemia, grade 3 (5%)
Diarrhea, grade 3 (4%)
Thrombocytopenia, grade 3 (2%)
Nausea, grade 3 (2%)
Fatigue, grades 3/4 (2%)
Asthenia, grade 3 (2%)
Upper respiratory treact infection, grade 3 (1%)
Decreased appetite, grade 3 (1%)
Warnings
Contraindications
None
Cautions
Neutropenia observed in clinical trials; febrile neutropenia also reported; monitor CBC count prior to starting drug and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated; dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop grade 3 or 4 neutropenia
Pulmonary embolism reported at a higher rate in patients treated with palbociclib plus letrozole (5%) or plus fulvestrant (1%) compared with no cases with either letrozole or fulvestrant alone
Avoid concomitant use of strong CYP3A inhibitors; if coadministration cannot be avoided, reduce the palbociclib dose (see Dosage modifications)
Avoid coadministration with moderate or strong CYP3A inducers
Based on findings in animals and mechanism of action, palbociclib can cause fetal harm
Pregnancy and lactation
Pregnancy
Based on findings in animals and mechanism of action, palbociclib can cause fetal harm when administered to a pregnant woman
In animal studies, palbociclib was teratogenic and fetotoxic at maternal exposures that were ≥4 times the human clinical exposure based on AUC at the recommended human dose
Advise females of reproductive potential to use effective contraception during treatment and for at least 2 weeks after the last dose; advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment
Males: Based on findings in animals, male fertility may be compromised by treatment
Lactation
Unknown if distributed in human breast milk; because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from palbociclib, advise a nursing woman to discontinue breastfeeding during treatment
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ibrance (palbociclib)
Mechanism of action
Cyclin dependent kinases (CDK) 4,6 inhibitor
Reduces cellular proliferation of ER-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle
Absorption
Bioavailability: 46%
Peak plasma time: 6-12 hr
Steady-state achieved: 8 days
Distribution
Protein bound: 85%
Vd: 2583 L
Metabolism
Extensively metabolized, primarily by CYP3A and SULT2A1
Elimination
Half-life: 29 hr
Oral clearance: 63.1 L/hr
Excretion: 74.1% feces (2.3% unchanged); 17.5% urine (6.9% unchanged)
Administration
Instructions
Take with food
Swallow capsules whole; do not chew, crush, or open them prior to swallowing
Do not ingest capsule if it is broken, cracked, or otherwise not intact
Missed or vomited dose: An additional dose should NOT be taken that day; the next prescribed dose should be taken at the usual time