Overview
11 DESCRIPTION IBRANCE tablets for oral administration contain 125 mg, 100 mg, or 75 mg of palbociclib, a kinase inhibitor. The molecular formula for palbociclib is C 24 H 29 N 7 O 2 . The molecular weight is 447.54 daltons. The chemical name is 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}pyrido[2,3- d ]pyrimidin-7(8 H )-one, and its structural formula is: Palbociclib...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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.
Indications
- 1 INDICATIONS AND USAGE IBRANCE is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with: • an aromatase inhibitor as initial endocrine-based therapy; or • fulvestrant in patients with disease progression following endocrine therapy. IBRANCE is indicated in combination with inavolisib and fulvestrant for the treatment of adult patients with endocrine-resistant, PIK3CA -mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer,...
Common Doses
- 125 mg
- 500 mg
- 100 mg
- 75 mg
Dosage
2 DOSAGE AND ADMINISTRATION IBRANCE tablets are taken orally with or without food in combination with an aromatase inhibitor, fulvestrant, or inavolisib and fulvestrant. ( 2 ) • Recommended starting dose: 125 mg once daily taken with or without food for 21 days followed by 7 days off treatment. ( 2.1 ) • Dosing interruption and/or dose reductions are recommended based on individual safety and tolerability. ( 2.2 ) 2.1 Recommended Dose and Schedule The recommended dose of IBRANCE is a 125 mg tablet taken orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a...
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Neutropenia [see Warnings and Precautions (5.1) ] • ILD/Pneumonitis [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥20%) in combination with either letrozole or fulvestrant, including laboratory abnormalities, were white blood cell count decreased, neutrophils decreased, blood creatinine increased, hemoglobin decreased, platelets decreased, infections, aspartate aminotransferase increased, alanine aminotransferase increased, fatigue, nausea,...
Interactions
- 7 DRUG INTERACTIONS Palbociclib is primarily metabolized by CYP3A and sulfotransferase (SULT) enzyme SULT2A1. In vivo, palbociclib is a time-dependent inhibitor of CYP3A. • CYP3A Inhibitors: Avoid concurrent use of IBRANCE with strong CYP3A inhibitors. If the strong inhibitor cannot be avoided, reduce the IBRANCE dose. ( 2.2 , 7.1 ) • CYP3A Inducers: Avoid concurrent use of IBRANCE with strong CYP3A inducers. ( 7.2 ) • CYP3A Substrates: The dose of sensitive CYP3A4 substrates with narrow therapeutic indices may need to be reduced when given concurrently with IBRANCE. ( 7.3 ) 7.