Dosing & Uses
Dosage Forms & Strengths
capsule
- 75mg
- 100mg
- 125mg
Breast Cancer
Indicated for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women, or with fulvestrant in women 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
Initial endocrine-based therapy in combination with an aromatase inhibitor: Refer to aromatase inhibitor (eg, letrozole, anastrozole, exemestane) prescribing information for dose
Disease progression following endocrine therapy: When given with palbociclib, the fulvestrant dose is 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 15 of first 2 cycles: If grade 3 on Day 15, continue at current dose to complete cycle; repeat complete blood count on Day 22; if grade 4 on Day 22, see grade 4 dose modifications below
- 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
- *Above refers to all hematologic adverse reactions 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 coadministration with strong CYP3A inhibitors and consider an alternant 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
Hepatic impairment
- Mild or moderate (Child-Pugh A or B): No dose adjustment required
- Severe (Child-Pugh C): Reduce dose to 75 mg/day for Days 1-21 of each 28-day cycle
Renal impairment
- Mild, moderate, or severe (CrCl >15 mL/min): No dose adjustment required
- Hemodialysis: Not studied
Dosing Considerations
Pre/perimenopausal women treated with palbociclib plus fulvestrant therapy should be treated with LHRH agonists according to current clinical practice standards
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
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse 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
Based on findings in animals and mechanism of action, palbociclib can cause fetal harm
Drug interaction overview
- In vitro data indicate that CYP3A and SULT enzyme SULT2A1 are mainly involved in the metabolism of palbociclib
- Palbociclib is also a weak time-dependent inhibitor of CYP3A following daily 125 mg dosing to steady state in humans
- 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
- Palbociclib may increase sensitive CYP3A substrates with a narrow therapeutic index (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine, sirolimus, and tacrolimus)
Pregnancy & 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
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
Oral Administration
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
Images
Patient Handout
Formulary
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