palbociclib

Adult Dosing

ER-Positive, HER2-Negative Advanced Breast Cancer

Initial Dose: 125 mg PO qd with food x 21 consecutive days followed by 7 days off treatment + 2.5 mg letrozole qd continuously throughout the 28-day cycle

Note:

The dose should preferably be taken around the same time each day.
Reduce the dose in case of any adverse reactions; taper to 100 mg followed by 75 mg; discontinue therapy if dose of 75 mg/day cannot be tolerated
In case of vomiting or a missed dose, an additional dose should not be taken that day; the next prescribed dose should be taken at the usual time
Refer package insert for dose modification and drug toxicity information

Pediatric Dosing

Safety and efficacy in pediatric patients have not been established

[Outline]

Adult Dosing
Pediatric Dosing

Indications ⬆ ⬇

Initial endocrine-based therapy for postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer used in combination with letrozole

Contraindications ⬆ ⬇

Hypersensitivity to any of the ingredients of the product

Black Box Warnings ⬆ ⬇

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment (Based on CrCl)

Mild renal impairment: CrCl 60-89 mL/min: No dose adjustments
Moderate renal impairment: CrCl 30-59 mL/min: No dose adjustments Severe renal impairment: Dose adjustment not defined

Hepatic Dose Adjustment

Mild hepatic impairment: Total bilirubin >1-1.5 x ULN or AST > ULN: No dose adjustments
Moderate-severe hepatic impairment: Total bilirubin >1.5 x ULN and any AST: Dose adjustment not defined

Warnings/Precautions ⬆ ⬇

Neutropenia Grade 3 or 4 and febrile neutropenia have been reported with palbociclib. Monitor CBC before starting the therapy, at the beginning of each cycle, on Day 14 of the first two cycles, and as clinically indicated. Consider dose interruption, dose reduction, or delay in initiating therapy cycles in patients who develop Grade 3 or 4 neutropenia
Higher rate of infection has been reported in patients treated with palbociclib plus letrozole compared to patients treated with letrozole alone. Monitor patients for signs and symptoms of infection and treat as medically appropriate
Higher rate of pulmonary embolism has been reported in patients treated with palbociclib plus letrozole compared with no cases in patients treated with letrozole alone. Monitor patients for signs and symptoms of pulmonary embolism and treat as medically appropriate
Inform women of reproductive potential about the drug-related risk to a fetus and advise them to use effective contraception during the therapy and for at least two weeks after the last dose

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category:NR (Not rated)Human data regarding the drug-associated risk to a fetus are not available, however, pregnant women should be informed about the potential risk to a fetus.

Breastfeeding: Safety unknown. Manufacturer advises to discontinue breastfeeding during treatment.

Adverse Reactions ⬆ ⬇

HEMA: Neutropenia, leukopenia, thrombocytopenia, anemia
RESP: Pulmonary embolism,URTI
EENT: Epistaxis
GI: Stomatitis, nausea, diarrhea, decreased appetite, vomiting
DERM: Alopecia
CNS: Peripheral neuropathy
MISC: Fatigue, infection, asthenia

Clinical Pharmacology ⬆ ⬇

Cyclin-dependent kinase (CDK) 4 and 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
Absolute bioavailability: 46%
Metabolism:Metabolized in liver by CYP3A and SULT2A1
Excretion: Excreted mainly in feces (74.1%) and urine (17.5%)
Half life: 29 (+/- 5) hours

Brands and Availability ⬆ ⬇