Dosing & Uses
Dosage Forms & Strengths
capsule
- 75mg
- 100mg
- 125mg
tablet
- 75mg
- 100mg
- 125mg
Breast Cancer
Indication
- Indicated for treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as follows:
-
Men or postmenopausal women
- Use in combination with aromatase inhibitor as initial endocrine-based therapy
-
Patients with disease progression following endocrine therapy
- Use in combination with fulvestrant
Combination therapy with aromatase inhibitor
- Palbociclib 125 mg PO qDay for Days 1-21 of each 28-day cycle
- Aromatase inhibitor: See prescribing information
- Continue until disease progression or unacceptable toxicity
- Men treated with combination palbociclib plus aromatase inhibitor therapy, consider treatment with a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards
Combination therapy with fulvestrant
- Palbociclib 125 mg PO qDay for Days 1-21 of each 28-day cycle
- Fulvestrant 500 mg IM on Days 1, 15, and 29, and then once monthly thereafter
- Continue until disease progression or unacceptable toxicity
- Pre/perimenopausal women treated with the combination palbociclib plus fulvestrant should also be treated with an LHRH agonist according to current clinical practice standards
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 treatment
Hematologic toxicities
- Grade 1 or 2: No dose adjustment required
-
Grade 3*:
- Day 1 of cycle: Withhold dose, repeat CBC within 1 week; when recovered to grade ≤2, start next cycle at same dose
- Day 15 of first 2 cycles: If grade 3 on Day 15, continue at current dose to complete cycle; repeat CBC on Day 22; if grade 4 on Day 22, see grade 4 dose modifications below
- Prolonged (>1 week) recovery from grade 3 or recurrent grade 3 neutropenia in subsequent cycles: Consider dose reduction
- 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 use with strong CYP3A inhibitors and consider an alternative with no or minimal CYP3A inhibition
- If coadministration cannot be avoided, 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
Interstitial lung disease (ILD) or pneumonitis
- Permanently discontinue treatment in patients with severe ILD/pneumonitis
Dosing Considerations
Monitor CBC 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
Adverse effects listed are for all grades of toxicity unless otherwise noted
>10% (Palbociclib with Letrozole)
WBC decreased (97%)
Neutrophils decreased (95%)
Neutropenia (80%)
Platelets decreased (63%)
Infections (60%)
Neutropenia, Grade 3 (56%)
Neutrophils decreased, Grade 3 (56%)
AST increased (52%)
ALT increased (43%)
Leukopenia (39%)
Fatigue (37%)
Nausea (35%)
WBC decreased, Grade 3 (35%)
Alopecia (33%)
Stomatitis (30%)
Diarrhea (26%)
Anemia (24%)
Leukopenia, Grade 3 (24%)
Rash (18%)
Asthenia (17%)
Vomiting (16%)
Thrombocytopenia (16%)
Dry skin (12%)
Pyrexia (12%)
>10% (Palbociclib with Fulvestrant)
WBC decreased (99%)
Neutrophils decreased (96%)
Neutropenia (83%)
Anemia (78%)
Platelets decreased (62%)
Neutrophils decreased, Grade 3 (56%)
Neutropenia, Grade 3 (55%)
Leukopenia (53%)
Infections (47%)
WBC decreased, Grade 3 (45%)
AST increased (43%)
Fatigue (41%)
ALT increased (36%)
Nausea (34%)
Leukopenia, Grade 3 (30%)
Anemia (30%)
Stomatitis (28%)
Diarrhea (24%)
Vomiting (19%)
Thrombocytopenia (23%)
Alopecia (18%)
Rash (17%)
Decreased appetite (16%)
Pyrexia (13%)
Neutropenia, Grade 4 (11%)
Neutrophils decreased, Grade 4 (11%)
1-10% (Palbociclib with Letrozole)
Neutropenia, Grade 4 (10%)
Anemia, Grade 3 (5%)
Infections, Grade 3 or 4 (1-6%)
AST increased, Grade 3 (3%)
ALT increased, Grade 3 (2%)
Thrombocytopenia, Grade 3 (1%)
Stomatitis, Grade 3 (1%)
Diarrhea, Grade 3 (1%)
Vomiting, Grade 3 (1%)
Leukopenia, Grade 4 (1%)
Rash, Grade 3 (1%)
WBC decreased, Grade 4 (1%)
Neutrophils decreased, Grade 4 (1%)
Platelets decreased, Grade 3 or 4 (1%)
1-10% (Palbociclib with Fulvestrant)
Asthenia (7.5%)
AST increased (7.5%)
Dysgeusia (6.7%)
Epistaxis (6.7%)
Lacrimation increased (6.4%)
Dry skin (6.1%)
ALT increased (5.8%)
Vision blurred (5.8%)
Anemia, Grade 3 (4%)
AST increased, Grade 3 (4%)
Dry eye (3.8%)
Infections, Grade 3 or 4 (1-3%)
Anemia, Grade 3 (3%)
Platelets decreased, Grade 3 (2%)
ALT increased, Grade 3 (2%)
Thrombocytopenia, Grade 3 (2%)
Fatigue, Grade 3 (2%)
Leukopenia, Grade 4 (1%)
Decreased appetite, Grade 3 (1%)
Vomiting, Grade 3 (1%)
Stomatitis, Grade 3 (1%)
Rash, Grade 3 (1%)
WBC decreased, Grade 4 (1%)
<1% (Palbociclib with Letrozole)
Anemia, Grade 4
Thrombocytopenia, Grade 4
Nausea, Grade 3
ALT increased, Grade 4
<1% (Palbociclib with Fulvestrant)
Pyrexia, Grade 3
Infections, Grade 4
Febrile neutropenia
Postmarketing Reports
Interstitial lung disease (ILD)/non-infectious pneumonitis
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 15 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; patients should promptly report any episodes of fever
Grade 3 and 4 infections reported when administered in combination with an antiestrogen compared to patients receiving antiestrogen only; monitor and manage appropriately symptoms and signs of infection
Nausea, vomiting, diarrhea, and grade 1 or 2 stomatitis reported in clinical trials
Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, when taken in combination with endocrine therapy
Additional cases of ILD/pneumonitis have been observed in the postmarketing setting, with fatalities reported; monitor for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough, and dyspnea; permanently discontinue therapy in patients with severe ILD or pneumonitis
Based on findings in animals and mechanism of action, palbociclib can cause fetal harm (see Pregnancy)
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 use with strong CYP3A inhibitors; if coadministration cannot be avoided, reduce the palbociclib dose (see Dosage Modifications)
- Avoid use 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
Females of reproductive potential should have a pregnancy test before starting treatment
Based on findings in animals, male fertility may be compromised by treatment
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for at least 3 weeks after the last dose
- Male patients with female partners of reproductive potential: Because of potential for genotoxicity, use effective contraception during treatment and for 3 months after the last dose
Infertility
- Males: Based on animal studies, may impair fertility in males of reproductive potential
Lactation
Unknown if distributed in human breast milk; because many drugs are excreted in human milk
Owing to the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking palbociclib and for at least 3 weeks after the last dose
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 (patients with advanced breast cancer)
Oral clearance: 63.1 L/hr
Excretion: 74.1% feces (2.3% unchanged); 17.5% urine (6.9% unchanged)
Majority of the dose eliminated in feces was metabolites
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
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
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Patient Handout
Formulary
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