FDA approves Ibrance for postmenopausal women with advanced breast cancer.

Approval Date: February 3, 2015

  • Palbociclib, a kinase inhibitor. The molecular formula for palbociclib is C24H29N7O2. The molecular weight is 447.54 daltons.

The chemical name is 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one, and its structural formula is:

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——————————-Mechanism of Action —————————————-

  • Palbociclib is an inhibitor of cyclin-dependent kinase (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 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.

————————————-INDICATIONS AND USAGE———————————- 

  • IBRANCE is a kinase inhibitor indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.
  • This indication is 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 a confirmatory trial.

 ———————–DOSAGE AND ADMINISTRATION ———————————— 

  • IBRANCE capsules are taken orally with food in combination with letrozole.
  • Recommended starting dose: 125 mg once daily taken with food for 21 days followed by 7 days off treatment.
  • Dosing interruption and/or dose reductions are recommended based on individual safety and tolerability.

      —————————–DOSAGE FORMS AND STRENGTHS——————————

  • Capsules: 125 mg, 100 mg, and 75 mg.

        —————————–WARNINGS AND PRECAUTIONS ——————————–

  • Hematologic: Neutropenia may occur. Monitor complete blood count prior to start of IBRANCE therapy and at the beginning of each cycle, as well as on Day 14 of the first two cycles, and as clinically indicated.
  • Infections: Monitor for signs and symptoms and withhold dosing as appropriate.
  • Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. 

 

 ——————————–ADVERSE REACTIONS ————————————— 

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

 ————————————DRUG INTERACTIONS————————————

  • CYP3A Inhibitors: Avoid concurrent use of IBRANCE with strong CYP3A inhibitors. If the strong inhibitor cannot be avoided, reduce the IBRANCE dose.
  • CYP3A Inducers: Avoid concurrent use of IBRANCE with strong and moderate CYP3A inducers.
  • CYP3A Substrates: The dose of sensitive CYP3A4 substrates with narrow therapeutic indices may need to be reduced when given concurrently with IBRANCE.

Ibrance is marketed by New York City-based Pfizer, Inc.

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