Uses of Palboxen: - Breast cancer Indicated for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer, in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women, or with fulvestrant in women with disease progression endocrine therapy Pregnancy and lactation.

Targeted Cancer Therapy

Treatment of breast cancer cell lines with the combination of palbociclib and antiestrogens leads to decreased retinoblastoma protein (Rb) 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 leads to increased cell senescence, which was sustained for up to 6 days following drug removal. 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.Palbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein.

How to use Palbociclib: Take this medicine in the dose and duration as advised by your doctor. Do not chew, crush or break it. Palbociclib is to be taken with food. Administration: Hard Capsule: Should be taken with food. Take at the same time each day. Swallow whole, do not chew/crush/open. Avoid grapefruit products. Adult Dose: Oral Hormone receptor positive, HER2-negative locally advanced carcinoma of breast, Hormone receptor positive, HER2-negative metastatic carcinoma of breast Adult: In combination with aromatase inhibitor, or in combination with fulvestrant in women who have received prior endocrine therapy: 125 mg once daily for 21 days, followed by 7 days off, repeat every 28 days until disease progression or unacceptable toxicity. Dosage Modifications Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline). Recommended dose reduction: 1st reduction: 100 mg once daily; 2nd reduction: 75 mg once daily; discontinue if dose reduction below 75 mg once daily is required. Hepatic impairment Mild or moderate (Child-Pugh A or B): No dose adjustment required Severe (Child-Pugh C): Reduce dose to 75 mg/day for Days 1-21 of each 28-day cycle Renal Dose: Renal impairment Mild, moderate, or severe (CrCl >15 mL/min): No dose adjustment required Hemodialysis: Not studied

Increased plasma concentration and systemic exposure with strong CYP3A inhibitors (e.g. clarithromycin, telithromycin, itraconazole, ketoconazole, posaconazole, voriconazole, indinavir, ritonavir, ritonavir-boosted lopinavir, nelfinavir, saquinavir, telaprevir, nefazodone, verapamil). Decreased plasma concentration with moderate CYP3A inducers (e.g. bosentan, efavirenz, etravirine, modafinil, nafcillin) or strong CYP3A inducers (e.g. carbamazepine, phenytoin, enzalutamide, rifampicin). May increase the plasma concentration of CYP3A substrates (e.g. ciclosporin, everolimus, sirolimus, tacrolimus, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine).

Pregnancy and lactation.

Common - Fatigue - Hair loss - Rash - Vomiting - Diarrhea - Nausea - Decreased blood cells (red cells, white cells, and platelets) - Infection - Decreased appetite - Fever >10% Neutropenia, all grades (75%) Neutropenia, grade 3 (48%) Leukopenia, all grades (43%) Fatigue, all grades (41%) Anemia, all grades (35%) Upper respiratory tract infection, all grades (31%) Stomatitis, all grades (25%) Nausea, all grades (25%) Alopecia, grade 1 (22%) Diarrhea, all grades (21%) Leukopenia, grade 3 (19%) Thrombocytopenia, all grades (17%) Decreased appetite, all grades (16%) Vomiting, all grades (15%) Peripheral neuropathy, all grades (13%) Asthenia, all grades (13%) Epistaxis, all grades (11%) 1-10% Neutropenia, grade 4 (6%) Anemia, grade 3 (5%) Diarrhea, grade 3 (4%) Thrombocytopenia, grade 3 (2%) Nausea, grade 3 (2%) Fatigue, grades 3/4 (2%) Asthenia, grade 3 (2%) Upper respiratory treact infection, grade 3 (1%) Decreased appetite, grade 3 (1%)

Lactation: Advise not to breastfeed

Precaution: Neutropenia observed in clinical trials; febrile neutropenia also reported; monitor CBC count prior to starting drug and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated; dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop grade 3 or 4 neutropenia

There is no known antidote for Palbociclib. The treatment of overdose of Palbociclib should consist of general supportive measures.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Palbociclib is a reversible, selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. Cyclin D1, CDK 4 and 6 are downstream of multiple signalling pathways which lead to cellular proliferation. Inhibition of CDK4/6 reduces proliferation of breast cancer cell lines by blocking progression from G1 into S phase of the cell cycle.

Palbociclib can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.