Palbociclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Cyclin D1 and CDK4/6 are downstream of signaling pathways which lead to cellular proliferation. In vitro, Palbociclib reduced cellular proliferation of estrogen receptor (ER)-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle. Treatment of breast cancer cell lines with the combination of Palbociclib and antiestrogens leads to decreased retinoblastoma (Rb) protein phosphorylation resulting in reduced E2F expression and signaling, and increased growth arrest compared to treatment with each drug alone. In vitro treatment of ER-positive breast cancer cell lines with the combination of Palbociclib and antiestrogens led to increased cell senescence compared to each drug alone, which was sustained for up to 6 days following Palbociclib removal and was greater if antiestrogen treatment was continued. In vivo studies using a patient-derived ER-positive breast cancer xenograft model demonstrated that the combination of Palbociclib and letrozole increased the inhibition of Rb phosphorylation, downstream signaling, and tumor growth compared to each drug alone. Human bone marrow mononuclear cells treated with Palbociclib in the presence or absence of an anti-estrogen in vitro did not become senescent and resumed proliferation following Palbociclib withdrawal.
Palbociclib is indicated for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in combination with:
• an aromatase inhibitor as initial endocrine based therapy in postmenopausal women; or
• fulvestrant in women with disease progression following endocrine therapy.
The recommended dose of Palbociclib is a 125 mg capsule taken orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days. Palbociclib should be taken with food. Administer the recommended dose of an aromatase inhibitor when given with Palbociclib. Please refer to the Full Prescribing Information for the aromatase inhibitor being used. When given with Palbociclib, the recommended dose of fulvestrant is 500 mg administered on Days 1, 15, 29, and once monthly thereafter. Please refer to the Full Prescribing Information of fulvestrant. Pre/perimenopausal women treated with the combination Palbociclib plus fulvestrant therapy should be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards.
Warnings & Precautions:
• Neutropenia: Complete blood count should be monitored prior to start of Palbociclib therapy and at the beginning of each cycle, as well as on Day 15 of the first 2 cycles, and as clinically indicated.
• Embryo-Fetal Toxicity: Palbociclib can cause fetal harm. Patients should be advised about potential risk to the fetus and to use effective contraception.
None
Based on findings from animal studies and its mechanism of action, Palbociclib can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk.
There is no information regarding the presence of Palbociclib in human milk, its effects on milk production, or the breastfed infant. Because of the potential for serious adverse reactions in breastfed infants from Palbociclib, advise a lactating woman not to breastfeed during treatment with Palbociclib and for 3 weeks after the last dose.
Palbokin 125 capsule: Each box contains 3x7’s capsules in blister pack.
Most common adverse reactions (incidence ≥10%) were neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anemia, alopecia, diarrhea, thrombocytopenia, rash, vomiting, decreased appetite, asthenia, and pyrexia.
CYP3A Inhibitors: Avoid concurrent use of Palbociclib with strong CYP3A inhibitors. If the strong inhibitor cannot be avoided, reduce the Palbociclib dose. CYP3A Inducers: Avoid concurrent use of Palbociclib with strong CYP3A inducers.
There is no known antidote for Palbociclib. The treatment of overdose of Palbociclib should consist of general supportive measures.
The safety and effectiveness of Palbociclib in pediatric patients have not been established.
Do not Store above 30° C. Protect from light. Keep out of the reach of children.
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