PALBONIX 125

Indications

• HR-positive, HER2-negative advanced or metastatic breast cancer
• Combination therapy with aromatase inhibitors or letrozole

Dosage

Children: Not established; refer to the BNF for Children for any applicable information.

Adults: Refer to specific clinical guidelines or the BNF for detailed dosing information.

Mechanism of action

Palbociclib selectively inhibits CDK4 and CDK6, proteins crucial for cell cycle progression. This inhibition prevents the phosphorylation of the retinoblastoma (Rb) protein, leading to cell cycle arrest in the G1 phase. As a result, tumor cell proliferation is inhibited, particularly in HR-positive breast cancer cells that require estrogen signaling for growth.

Pharmacodynamics

The pharmacodynamic effects of palbociclib include cell cycle arrest in the G1 phase, resulting in reduced tumor cell proliferation. This is particularly effective in HR+/HER2- breast cancer, where the growth of cancer cells is often driven by estrogen. The combination with aromatase inhibitors or selective estrogen receptor modulators enhances the therapeutic effect by targeting different pathways involved in tumor growth.

Pharmacokinetics

Palbociclib is administered orally and has a bioavailability of approximately 46%. It is extensively metabolized in the liver, primarily by CYP3A4, and has a half-life of about 29 hours. The drug is eliminated mainly via fecal excretion, with renal excretion accounting for a minor fraction. Dose adjustments may be necessary in patients with hepatic impairment due to its metabolism.

Contra-indications

• Hypersensitivity to palbociclib or any of its components
• Severe hepatic impairment

Adverse effects

• Neutropenia
• Anemia
• Thrombocytopenia
• Fatigue
• Nausea
• Vomiting
• Diarrhea
• Stomatitis
• Rash
• Pulmonary embolism

Interactions

• CYP3A4 inhibitors may increase palbociclib levels, leading to increased toxicity
• CYP3A4 inducers may decrease palbociclib levels, reducing efficacy
• Avoid concomitant use with strong CYP3A4 inducers such as rifampicin or St. John's wort
• Caution advised when used with other drugs known to affect CYP3A4 metabolism

Precautions

• Monitor complete blood counts regularly due to risk of neutropenia
• Assess liver function before and during treatment, particularly in patients with pre-existing liver disease
• Use caution in patients with a history of thromboembolic events
• Monitor for signs of infection due to potential immunosuppression

Pregnancy

Palbociclib may cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 weeks after the last dose.

Breast-feeding

It is not known whether palbociclib is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store at room temperature (20°C to 25°C), in a tightly closed container, protected from moisture and light.

Formulations

• Capsules: 125 mg, 100 mg, 75 mg