Instructions for Palbociclib

1. Common name: palbociclib

Product name:IBRANCE

All names: palbociclib, palbociclib, palbociclib, palbociclib, iboxin

2. Indications:

Palbociclib (Palbociclib) is indicated for the treatment of adult patients with hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer. Palbociclib may be used with an aromatase inhibitor as initial endocrine therapy in postmenopausal women or men, or in combination with fulvestrant in patients whose disease has progressed after endocrine therapy.

3. Usage and dosage:

1. Recommended dosage:

The recommended dose of palbociclib is a capsule of 125 mg taken orally once a day for 21 consecutive days, followed by a 7-day discontinuation of treatment, forming a complete 28-day cycle. This drug should be taken with food. Coadministration of palbociclib with an aromatase inhibitor at recommended doses requires reference to the full prescribing information for the aromatase inhibitor being used. When administered with palbociclib, the recommended dose of fulvestrant is 500 mg on days 1, 15, 29, and monthly thereafter.

According to current clinical practice standards, premenopausal/perimenopausal women receiving palbociclib plus fulvestrant should also receive luteinizing hormone-releasing hormone (LHRH) agonist therapy. For men receiving palbociclib plus an aromatase inhibitor, consider treatment with an LHRH agonist in accordance with current clinical practice standards.

2. Dosage adjustment:

If patients experience adverse reactions during treatment with palbociclib, the dose should be adjusted under the guidance of a doctor. The first dose should be reduced to 100 mg orally once a day, and the second dose should be reduced to 75 mg orally once a day; patients who cannot tolerate the second dose reduction should permanently discontinue palbociclib.

(1) StrongCYP3A inhibitor:

Avoid concomitant use of strong CYP3A inhibitors and consider concomitant use of alternative drugs with no or minimal CYP3A inhibition. If the patient must take a strong CYP3A inhibitor concurrently, the dose should be reduced to 75 mg once daily. If the strong inhibitor is discontinued, increase the palbociclib dose (after 3-5 half-lives of the inhibitor) to the dose before starting the strong CYP3A inhibitor.

(2) Patients with liver function impairment:

No dose adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh classes A and B). For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of palbociclib is 75 mg once daily for 21 days, followed by 7 days off treatment, constituting a complete 28-day cycle.

4. Adverse reactions:

In clinical studies, when palbociclib was used in combination with an aromatase inhibitor (letrozole), the most common adverse reactions (≥10%) were neutropenia, infection, leukopenia, fatigue, nausea, alopecia, stomatitis, diarrhea, anemia, rash, asthenia, thrombocytopenia, vomiting, decreased appetite, dry skin, pyrexia, and dysgeusia.

In clinical studies, the most common adverse reactions (≥10%) when palbociclib was used in combination with fulvestrant were neutropenia, leukopenia, infection, fatigue, nausea, anemia, stomatitis, diarrhea, thrombocytopenia, vomiting, alopecia, rash, decreased appetite, and pyrexia.

5. Storage:

Palbociclib will be stored20°C to 25°C (68°F to 77°F); excursions allowed between 15°C and 30°C (59°F to 86°F).

6. Special groups:

1. Women: Pregnant women taking palbociclib can cause harm to the fetus. It is recommended that women of reproductive potential use effective contraceptive measures during palbociclib treatment and for at least 3 weeks after the last dose. Lactating women should not breastfeed for at least 3 weeks.

2. Males: Due to potential genotoxicity, male patients with female partners of reproductive potential are recommended to use effective contraceptive measures during palbociclib treatment and within 3 months after the last dose.

7. Mechanism of action:

Palbociclib is an inhibitor of cyclin-dependent kinase(CDK) 4 and 6. Cyclin D1 and CDK4/6 are downstream of signaling pathways leading to cell proliferation. In vitro, palbociclib reduces cell proliferation in estrogen receptor (ER)-positive breast cancer cell lines by preventing cells from entering the S phase of the cell cycle from G1. Treatment of breast cancer cell lines with the combination of palbociclib and antiestrogen resulted in reduced retinoblastoma (Rb) protein phosphorylation, resulting in reduced E2F expression and signaling, and increased growth arrest compared to treatment with each drug alone.