Palbonix palbociclib Beacon polbociclib inn 125mg

Generic Name: Palbociclib

Brand Name: Palbace

Generic English Name: palbociclib

Other Names: Palbociclib, Ibrance

Specification: 125 mg/capsule; 21 capsules/box

[Composition] The main active ingredient of this product is palbociclib.

Chemical Name: 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one

Molecular Formula: C24H29N7O2

Molecular Weight: 447.54 g/mol.

[Indications/Therapeutic Uses]

Patients with advanced or metastatic breast cancer that is Human Epidermal Growth Factor Receptor 2 (HER2)-negative.

This indication was approved under accelerated approval based on Progression-Free Survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Clinical trials for other indications (non-small cell lung cancer, lymphoma, multiple myeloma) are currently ongoing.

[Dosage and Administration]

The recommended dose is 125 mg, taken orally once daily with food. Administer for 21 consecutive days, followed by a 7-day break.

If vomiting occurs or a dose is missed, do not take an additional dose on the same day to make up for the missed dose.

[Adverse Reactions]

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

[Contraindications] None.

[Precautions]

1. Hematologic: Neutropenia may occur. Monitor complete blood counts prior to the start of therapy, at the beginning of each cycle, on Day 14 of the first two cycles, and as clinically indicated.

2. Infections: Monitor for signs and symptoms of infection and administer appropriate treatment.

3. Embryo-Fetal Toxicity: May cause fetal harm. Advise patients regarding potential risks to the fetus and the use of effective contraception.

4. Pulmonary Embolism: Monitor patients for signs and symptoms of pulmonary embolism, and administer appropriate treatment based on the patient's clinical condition.

[Use in Pregnant and Lactating Women]

Use during Pregnancy: Currently, there are no available data on the use of this drug in pregnant women. Based on results from animal studies and its mechanism of action, it may cause fetal harm. Use during Lactation: Data regarding the secretion of this drug into human milk are unknown. Many drugs are excreted in breast milk; therefore, it is recommended that women discontinue breastfeeding while undergoing treatment.

[Use in Children] Currently, there are no available data regarding the safety and efficacy of this drug in pediatric patients.

[Use in the Elderly] No clinically significant differences in safety or efficacy were observed between elderly patients and younger patients. However, increased sensitivity in some elderly individuals cannot be ruled out.

[Use in Special Populations]

Hepatic Impairment: Based on a pharmacokinetic analysis of 183 patients—40 of whom had mild hepatic impairment—hepatic impairment had no effect on drug exposure. Pharmacokinetic studies have not been conducted in patients with moderate or severe hepatic impairment.

Renal Impairment: Based on a pharmacokinetic analysis of 183 patients—73 of whom had mild renal impairment (60 mL/min ≤ CrCl < 90 mL/min) and 29 of whom had moderate renal impairment (30 mL/min ≤ CrCl < 60 mL/min)—palbociclib had no effect on patients with mild or moderate renal impairment. Studies have not been conducted in patients with severe renal impairment.

[Pharmacological Action]

Palbociclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Cyclin D1 and CDK4/6 act downstream in cell proliferation signaling pathways. *In vitro* studies have demonstrated that palbociclib reduces the proliferation of estrogen receptor (ER)-positive breast cancer cell lines by blocking the progression of cells from the G1 phase into the S phase of the cell cycle.

Compared to monotherapy, the combination of palbociclib and anti-estrogen agents reduces retinoblastoma protein (Rb) phosphorylation in cancer cell lines, thereby decreasing E2F expression and inhibiting cell growth. [Pharmacodynamics]

Cardiac Electrophysiology: The effect of palbociclib on the QTc interval was evaluated in 184 patients with advanced cancer. Regarding the effect on the QTc interval, no clinically meaningful changes in the mean QT interval were observed.

[Pharmacokinetics]

Absorption and Distribution

Following oral administration of palbociclib, the mean Cmax is typically observed between 6 and 12 hours (Tmax). Following a single oral dose of 125 mg, the mean absolute bioavailability is 46%. Within the dose range of 25 mg to 225 mg, AUC and Cmax increase in proportion to the dose. Steady state is achieved within 8 days of once-daily dosing. With repeated daily dosing, the median accumulation ratio for palbociclib is 2.4 (range: 1.5–4.2).

Effect of Food: In approximately 13% of the population, palbociclib absorption and exposure are very low under fasting conditions. It may be taken with food.

In vitro binding to human plasma proteins is approximately 85%, with no concentration dependence observed over the range of 500 ng/mL to 5000 ng/mL. The geometric mean apparent volume of distribution (Vz/F) is 2583 L (26% CV).

Metabolism and Elimination

In vitro and in vivo studies indicate that palbociclib undergoes hepatic metabolism in humans. Following a single oral dose of 125 mg of [14C] palbociclib, the primary metabolic pathways are oxidation and sulfonation of palbociclib, while acylation and glucuronidation serve as minor pathways.

Palbociclib is the major circulating drug-derived entity in plasma (23%). The major circulating metabolite is a glucuronide conjugate of palbociclib, although it accounts for only 1.5% of the administered dose in excreta. Palbociclib metabolites account for 2.3% and 6.9% of the radioactivity in feces and urine, respectively. In feces, a sulfamic acid conjugate of palbociclib is the major drug-related component, accounting for 26% of the administered dose. In vitro studies using human hepatocytes, hepatocyte cytosol and S9 fractions, and recombinant SULT enzymes indicate that CYP3A and SULT2A1 are the primary enzymes involved in the metabolism of palbociclib.

The geometric mean oral clearance (CL/F) of palbociclib is 63.1 L/h (29% CV), and the mean (± standard deviation) plasma elimination half-life in patients with advanced breast cancer is 29 (± 5) hours. Following a single oral dose of [14C] palbociclib administered to 6 healthy male subjects, a median of 91.6% of the total administered radioactive dose was recovered within 15 days; feces (accounting for 74.1%) constituted the primary route of excretion, with 17.5% of the dose recovered in urine. The majority of the recovered dose was excreted as metabolites.

Age, Gender, and Body Weight

Based on a population pharmacokinetic analysis of 183 cancer patients (50 males, 133 females; age range: 22–89 years; body weight range: 37.9–123 kg), gender had no effect on palbociclib exposure, nor did age or body weight have any clinically significant effect.

[Drug Interactions]

CYP3A Inhibitors: Avoid concomitant use with strong CYP3A inhibitors. If concomitant use with a strong inhibitor cannot be avoided, reduce the dose of palbociclib.

CYP3A Inducers: Avoid concomitant use with strong and moderate CYP3A inducers.

CYP3A Substrates: The dosage of sensitive CYP3A4 substrates with a narrow therapeutic index may need to be reduced when administered concomitantly with palbociclib.

[Overdosage] There is no known antidote. Management of overdose should include general supportive measures.

[Storage] Store at 20–25°C; excursions are permitted between 15°C and 30°C. Palbociclib (Palbonix) — Manufactured by Beacon Pharmaceuticals (Bangladesh)

Palbociclib (also known as Palbocent) is the world's first cyclin-dependent kinase (CDK) 4/6 inhibitor. It is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. It should be used in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women.

Breast cancer is the leading malignancy posing a serious threat to women's health worldwide. The situation regarding advanced breast cancer is even more dire, with an overall median survival of only 2–3 years and a 5-year survival rate of merely 20%.

CDK4/6 inhibitors have emerged in recent years as highly touted "miracle drugs" in cancer therapy. They are rapidly transforming the treatment landscape for HR+/HER2- advanced breast cancer by effectively overcoming or delaying the onset of endocrine resistance, thereby extending survival time for patients with advanced disease.

Based on the Phase II study PALOMA-1, the U.S. FDA granted accelerated approval on February 3, 2015, for palbociclib in combination with letrozole as a first-line treatment for postmenopausal ER+/HER2- advanced breast cancer. On February 19, 2016—based on a randomized, controlled Phase III study (PALOMA-3)—the FDA further approved palbociclib in combination with fulvestrant for the treatment of HR+/HER2- advanced breast cancer in postmenopausal women whose disease had progressed following prior endocrine therapy.

Due to its exceptional efficacy and safety profile, palbociclib has to date been approved for market launch in over 80 countries and regions worldwide. On July 31, 2018, the National Medical Products Administration (NMPA) of China approved the drug for market entry; China became the 87th country to approve palbociclib, and—as the only breakthrough innovative therapy for advanced breast cancer approved in China in the last decade—the drug has garnered significant attention. Palbonix, manufactured by Beacon Pharmaceuticals, is a generic version of palbociclib that has received legal approval for production from the regulatory authorities of the Bangladeshi government. Beacon Pharmaceuticals is backed by investment from a European consortium. It is the only major pharmaceutical enterprise in South Asia that strictly adheres to EU technical specifications and is listed on the main boards of Bangladesh's two major stock exchanges; its products comply with both European Pharmacopoeia and United States Pharmacopoeia standards. Compared to so-called generic equivalents from obscure or unverified sources—even if their active ingredient content appears similar to Beacon's products—there remain significant differences in critical parameters such as dissolution rate and bioavailability (which directly impact drug absorption). This disparity arises because these other products lack manufacturing facilities that meet rigorous GMP standards, as well as the strict regulatory oversight provided by government authorities.

To ensure medication safety, please choose with caution!

**Product Specifications**

**Product Name:** Palbociclib (Palbonix) 125mg * 21 Capsules | Beacon Pharmaceuticals | Palbociclib

**Common Name:** Palbociclib Capsules

**Composition:** Palbociclib

**Dosage Form:** Capsules

**Specification:** 125mg/capsule; 21 capsules/box

**Manufacturer:** Beacon Pharmaceuticals

**Indications:** For the treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

This indication was approved under an accelerated approval process based on Progression-Free Survival (PFS) data. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. (Clinical trials for other indications—including Non-Small Cell Lung Cancer, Lymphoma, and Multiple Myeloma—are currently underway.)

**Usage and Dosage:** The recommended dose is 125mg, taken orally once daily with food. Administer for 21 consecutive days, followed by a 7-day treatment-free interval.

If vomiting occurs or a dose is missed, do not take an additional dose on the same day to make up for the missed dose.