局部晚期或轉移性乳癌 Breast cancer, advanced
1. For HR-positive, HER2-negative females<20220317> or adult males (in combination with an aromatase inhibitor)
2. For HR-positive, HER2-negative adult patients (in combination with fulvestrant)
#仿單變更2021#仿單變更2022

Cyclin-Dependent Kinase Inhibitor:
Palbociclib is a reversible small molecule cyclin-dependent kinase (CDK) inhibitor which is selective for CDK 4 and 6. CDKs have a role in regulating progression through the cell cycle at the G1/S phase by blocking retinoblastoma (Rb) hyperphosphorylation. Palbociclib reduces proliferation of breast cancer cell lines by preventing progression from the G1 to the S cell cycle phase.

Absorption
1. Increased with high-fat, high-calorie food
2. Mean absolute bioavailability: 46%
Distribution
1. Vd (mean): 2,583 L
2. Protein binding: ~85%
Metabolism
Extensively hepatic; Major pathways: Oxidation and sulfonation, primarily by CYP3A and sulfotransferase (SULT) enzyme SULT2A1; Minor pathways: Acylation and glucuronidation
Excretion
Feces (~74%, primarily as metabolites); Urine (~18%; primarily as metabolites) Pharmacodynamics
1. Half-life elimination: 29 ± 5 hours
2. Time to peak: 6 to 12 hours

Adverse events were observed in animal reproduction studies. Based on the mechanism of action, palbociclib may be expected to cause fetal harm if used during pregnancy.
1. Pregnancy test is recommended prior to treatment initiation.
2. Use effective contraception during treatment and for at least 3 weeks after the last dose. (For females or males with female partners of reproductive potential)

It is not known if palbociclib is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for at least 3 weeks after the last dose.

Common
Fatigue, Alopecia, skin rash, xeroderma, gastrointestinal disorder(Nausea, stomatitis, diarrhea, vomiting, decreased appetite),neutropenia, anemia, leukopenia, thrombocytopenia, Increased serum ASTor ALT, infection, weakness, fever
Postmarketing
Pulmonary toxicity
1. Monitor closely for symptoms of ILD/pneumonitis (hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exam).
2. Interrupt therapy immediately for new or worsening respiratory symptoms which may be indicative of pneumonitis.
3. Permanently discontinue palbociclib for severe ILD/pneumonitis.<20210318>

Administration:
With food, do not open capsules prior to swallowing; If a dose is vomited or missed, an additional dose should not be taken that day, resume dosing with the next scheduled daily dose.
Dosage:
1. 125 mg once daily for 21 days, followed by 7 days off, repeat every 28 days; continue until disease progression or unacceptable toxicity
2. In combination with continuous aromatase inhibitor therapy OR with fulvestrant [and an LHRH agonist (eg, goserelin) if pre- or perimenopausal]<20220317>
3. For males: consider treatment of palbociclib + aromatase inhibitor + luteinizing hormone-releasing hormone (LHRH) agonist<20210830>

Safety and efficacy in pediatric patients are not established

1. CrCl >15 mL/minute: No dosage adjustment necessary.
2. CrCl ≤15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
3. Hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

1. Mild or moderate impairment (Child-Pugh classes A and B): No dosage adjustment necessary.
2. Severe impairment (Child-Pugh class C): Reduce dose to 75 mg once daily for 21 days, followed by 7 days off; repeat every 28 days.

Store between 15 and 30 °C