Name: Palbociclib Capsules

Specification: 21 capsules/bottle

Manufacturer: Pfizer Inc.

Indications:

Indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It may be used in combination in the following settings:

1. In combination with letrozole, for the treatment of estrogen receptor-positive (ER+) and HER2-negative advanced breast cancer in postmenopausal women;

2. In combination with fulvestrant, for the treatment of HR-positive, HER2-negative advanced breast cancer in postmenopausal women whose disease has progressed following prior endocrine therapy.

Dosage and Administration:

Recommended Starting Dose: 125 mg orally once daily for 21 consecutive days, followed by 7 days off treatment (a 3/1 dosing schedule), constituting a 28-day treatment cycle. Treatment should be continued unless the patient no longer derives clinical benefit or experiences unacceptable toxicity.

When used in combination with letrozole, the recommended dose of letrozole is 2.5 mg orally once daily, taken continuously throughout the entire 28-day treatment cycle.

Palbociclib capsules should be swallowed whole (do not chew, crush, or open the capsules prior to swallowing). Do not ingest any capsule that is broken, cracked, or otherwise appears to be damaged. Patients are advised to take the medication at approximately the same time each day. If a patient vomits or misses a dose, they should not take an additional dose on that day. The next scheduled dose should be taken as usual.

If adverse reactions occur, the dose should be reduced. The recommended starting dose is 125 mg/day. The first dose reduction is to 100 mg/day; the second dose reduction is to 75 mg/day; if a patient requires a reduction below 75 mg/day, the medication should be discontinued.

Adverse Reactions:

Common adverse reactions (incidence ≥10%) include neutropenia, leukopenia, fatigue, anemia, upper respiratory tract infection, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, asthenia, peripheral neuropathy, and epistaxis.

Precautions:

1. Neutropenia

Decreased neutrophil counts have been observed in clinical trials of palbociclib. In a randomized clinical trial (Study 1), patients receiving IBRANCE plus letrozole reported Grade 3 (57%) or Grade 4 (5%) decreases in neutrophil counts. The median time to the first onset of any-grade neutropenia, based on laboratory data, was 15 days (range: 13–117 days). The median time to Grade ≥3 neutropenia was 7 days. Febrile neutropenia events have been reported in the palbociclib clinical program, although no cases of febrile neutropenia were observed in Study 1. Monitor complete blood counts prior to the start of palbociclib treatment, at the beginning of each cycle, on Day 14 of the first two cycles, and as clinically indicated. For patients who develop Grade 3 or 4 neutropenia, dose interruption, dose reduction, or a delay in the start of the treatment cycle is recommended.

2. Infections

In Study 1, a higher rate of infections was reported in patients treated with palbociclib plus letrozole compared to patients treated with letrozole alone. Grade 3 or 4 infections occurred in 5% of patients treated with palbociclib plus letrozole, whereas no patients treated with letrozole alone experienced Grade 3 or 4 infections. Monitor patients for signs and symptoms of infection and treat as medically appropriate.

3. Pulmonary Embolism

In Study 1, a higher rate of pulmonary embolism (5%) was reported in patients treated with palbociclib plus letrozole, compared to no cases in patients treated with letrozole alone. Monitor patients for signs and symptoms of pulmonary embolism and treat as medically appropriate.

4. Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, palbociclib may cause fetal harm. In rats and rabbits, palbociclib caused embryo-fetal toxicity at maternal exposures (based on Area Under the Curve [AUC]) that were greater than or equal to 4 times the human clinical exposure. Women of reproductive potential are advised to use effective contraception during treatment with Palbociclib and for at least 2 weeks following the last dose.

Product Specifications

Product Name: Palbociclib Capsules 125 mg (21 capsules) — Pfizer Original Product (Pfizer Palbace 125 mg)

Common Name: Palbociclib Capsules

Active Ingredient: Palbociclib

Dosage Form: Capsules

Specification: 21 capsules/bottle

Manufacturer: Pfizer Pharmaceuticals

Indications: Palbociclib is a cyclin-dependent kinase (CDK) 4 and 6 inhibitor. Cyclin D1 and CDK4/6 are signaling molecules that drive cellular proliferation. In estrogen receptor-positive breast cancer cell lines, Palbociclib reduces cellular proliferation by blocking the progression of cells from the G1 phase into the S phase of the cell cycle. Treatment of estrogen receptor-positive breast cancer cell lines with Palbociclib in combination with anti-estrogen agents inhibits cancer cell growth and proliferation, and accelerates cancer cell senescence. The combination of Palbociclib and Letrozole also demonstrates inhibitory effects on tumor growth.

Dosage and Administration: Recommended starting dose: 125 mg taken orally once daily for 21 consecutive days, followed by a 7-day break (a 3/1 dosing schedule); a complete treatment cycle consists of 28 days. Treatment should be continued unless the patient no longer derives clinical benefit or experiences unacceptable toxicity.

When used in combination with Letrozole, the recommended dose of Letrozole is 2.5 mg, taken orally once daily, continuously throughout the entire 28-day treatment cycle.

Palbociclib capsules should be swallowed whole (do not chew, crush, or open the capsules prior to swallowing). Capsules that appear damaged, cracked, or otherwise compromised should not be taken. Patients are advised to take the medication at approximately the same time each day. If a patient vomits or misses a dose, they should not take an additional dose on that day to make up for it; the next scheduled dose should be taken as usual.

If adverse reactions occur, the dosage should be reduced. The recommended starting dose is 125 mg/day. Reduce by 100 mg/day initially; reduce by 75 mg/day subsequently; if the patient requires a reduction to 75 mg/day, discontinue the medication.