Palbociclib/Pabociclib/Palbociclib Instructions

1. Indications

Palbociclib/PabociclibTreatment of patients with hormone receptor(HR)positive, human epidermal growth factor receptor2 (HER2)Negative advanced or metastatic breast cancer in men or premenopausal/perimenopausal/postmenopausal women, in combination with an aromatase inhibitor as initial endocrine therapy. Palbocicillinin combination with fulvestrant is indicated for men or women whose disease has progressed after endocrine therapy.

2. UsageDosage

1.Combined treatment with aromatase inhibitors:

125mg palbocicillin orally once daily on days 1-21 of each 28 day cycle

Aromatase Inhibitors:See Prescribing Information

Continue until disease progression or unacceptable toxicity occurs

Based on current standards of clinical practice, treatment with a luteinizing hormone-releasing hormone (LHRH) agonist may be considered in men receiving palbocicillin in combination with an aromatase inhibitor.

Based on current standards of clinical practice, premenopausal/perimenopausal women who receive palbocicillin in combination with an aromatase inhibitor should also receive LHRH agonist treatment

2.Fulvestrant combination therapy:

125mg palbocicillin orally once daily on days 1-21 of each 28 day cycle

Intramuscular injection of fulvestrant on days 1, 15 and 29500 mgthen monthly

Continue until disease progression or unacceptable toxicity occurs

Based on current standards of clinical practice, premenopausal/perimenopausal women who receive palbocicillin combined with fulvestrant should also receive LHRHagonist treatment

Three. Dosage form and strength

Capsules: 125mg, 100mg and 75mg.

Four. Contraindications

None

Five. Warnings and Precautions

1.Neutropenia

Neutropenia was the most commonly reported adverse reaction in PALOMA-2 and PALOMA-3, occurring in 80% and 83%, respectively. Monitor complete blood counts before initiating treatment with IBRANCE and at the beginning of each cycle, and on Day 15 of the first two cycles, as clinically indicated. For patients who develop grade 3 or grade 4 neutropenia, dose interruption, dose reduction, or delayed initiation of the treatment cycle is recommended. Physicians should inform patients to promptly report any fever symptoms.

2.Interstitial lung disease(ILD)/Pneumonia

Severe, life-threatening, or fatal interstitial lung disease(ILD) and / or pneumonitis may occur in patients receiving cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including IBRANCE when used in combination with endocrine therapy. Monitor patients for ILD/pulmonary symptoms of pneumonia (such as hypoxia, cough, dyspnea). If a patient develops new or worsening respiratory symptoms and is suspected of having pneumonia, palbocicillin should be discontinued immediately and the patient evaluated. Patients with severeILDor pneumonia should permanently discontinue this product.

3.Embryo-Fetal toxicity

Based on findings from animal studies and its mechanism of action, palbocicillin can cause fetal harm when given to pregnant women. Inform pregnant women of potential risks to the fetus. Advise females of reproductive potential to use effective contraception during treatment with palbocicillin and for at least3 weeks after the last dose.

Adverse reactions

The most common side effects of palbocicillin (which may affect more than 1 in 5 people) are neutropenia, infection, leukopenia, fatigue, nausea, stomatitis, anemia, diarrhea, alopecia, and thrombocytopenia.

Palbociclib's most common serious side effects (may affect as many as1 in 50 people) are Neutropenia, leukopenia, infection, anemia, fatigue, and increased blood levels of liver enzymes(aspartate and alanine aminotransferase)blood levels.

7. drug interactions

CYP3AInhibitors:Avoid the concomitant use of palbocicillinwith strongCYP3Ainhibitors. If strong inhibitors cannot be avoided, reduce dose.

CYP3AInducers:Avoid the concomitant use of palbocicillinwith strongCYP3A inducers.

CYP3ASubstrates:The dose of sensitiveCYP3A4substrates with a narrow therapeutic index may need to be reduced when coadministered withpalbocicillin.

8. Used by specific groups of people

1.Pregnancy

Based on the results of animal studies and its mechanism of action, this product may cause harm to the fetus when taken by pregnant women.

2.Breastfeeding

There is no information about the presence of palbociclib in breast milk, its effects on milk production, or on the breastfed infant. Becausepalbociclibhas the potential for serious adverse reactions in breastfed infants, it is recommended that nursing women take palbociclibDo not breastfeed during treatment and for 3 weeks after the last dose.

3.Females and men of reproductive potential

According to animal studies, taking this product by pregnant women can cause harm to the fetus. Females of childbearing potential should have a pregnancy test before starting palbocicillin treatment. Advise females of reproductive potential to use effective contraception during IBRANCEtreatment and for at least 3 weeks after the last dose. Due to the potential for genotoxicity, advise male patients with a female partner of reproductive potential to use effective contraception during treatment with palbocicillin and for 3 months after the last dose.

9. clinical pharmacology

Mechanism of action

Palbocicillin is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Cyclin D1 and CDK4/6 are downstream of signaling pathways that lead to cell proliferation. In vitro, palbocicillin reduces cell proliferation in estrogen receptor (ER)-positive breast cancer cell lines by preventing cells from entering the S phase of the cell cycle. Treatment of breast cancer cell lines with the combination of palbocicillin and antiestrogen resulted in reduced retinoblastoma (Rb) protein phosphorylation, resulting in reduced E2F expression and signaling, and increased growth arrest compared with treatment with each drug alone. In vitro treatment of ERpositive breast cancer cell lines with the combination of palbocicliband antiestrogen compared with each drug alone resulted in increased cellular senescence that persisted for up to 6days after removal of palbociclib and was more severe if antiestrogen treatment was continued. In vivo studies using a patient-derived ERxenograft model of ERpositive breast cancer showed that the combination ofpalbocicillinand letrozole increased the inhibition ofRbphosphorylation, downstream signaling, and tumor growth compared with each drug alone. In vitro, human bone marrow mononuclear cells treated with palbocicillin do not senescence in the presence or absence of antiestrogens and resume proliferation after discontinuation of palbocicillin. Original drugs in Hong Kong cost about 1 or so, and generic drugs cost about 7 more than 7 more than 4 more than 1,000 per box. If you want to get more high-quality information, you can contact YaDE. YaDE will do its best to learn more about high-quality overseas drugs for you.