(palbociclib)
13 NONCLINICAL TOXICOLOGY
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Palbociclib was assessed for carcinogenicity in a 6-month transgenic mouse study and in a 2-year rat study. Oral administration of palbociclib for 2 years resulted in an increased incidence of microglial cell tumors in the central nervous system of male rats at a dose of 30 mg/kg/day (approximately 8 times the human clinical exposure based on AUC). There were no neoplastic findings in female rats at doses up to 200 mg/kg/day (approximately 5 times the human clinical exposure based on AUC). Oral administration of palbociclib to male and female rasH2 transgenic mice for 6 months did not result in increased incidence of neoplasms at doses up to 60 mg/kg/day.
Palbociclib was aneugenic in Chinese Hamster Ovary cells in vitro and in the bone marrow of male rats at doses ≥100 mg/kg/day for 3 weeks. Palbociclib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay and was not clastogenic in the in vitro human lymphocyte chromosome aberration assay.
In a fertility study in female rats, palbociclib did not affect mating or fertility at any dose up to 300 mg/kg/day (approximately 4 times human clinical exposure based on AUC) and no adverse effects were observed in the female reproductive tissues in repeat-dose toxicity studies up to 300 mg/kg/day in the rat and 3 mg/kg/day in the dog (approximately 6 times and similar to human exposure [AUC], at the recommended dose, respectively).
The adverse effects of palbociclib on male reproductive function and fertility were observed in the repeat-dose toxicology studies in rats and dogs and a male fertility study in rats. In repeat-dose toxicology studies, palbociclib-related findings in the testis, epididymis, prostate, and seminal vesicle at ≥30 mg/kg/day in rats and ≥0.2 mg/kg/day in dogs included decreased organ weight, atrophy or degeneration, hypospermia, intratubular cellular debris, and decreased secretion. Partial reversibility of male reproductive organ effects was observed in the rat and dog following a 4- and 12-week non-dosing period, respectively. These doses in rats and dogs resulted in approximately ≥10 and 0.1 times, respectively, the exposure [AUC] in humans at the recommended dose. In the fertility and early embryonic development study in male rats, palbociclib caused no effects on mating but resulted in a slight decrease in fertility in association with lower sperm motility and density at 100 mg/kg/day with projected exposure levels [AUC] of 20 times the exposure in humans at the recommended dose.
MEDICATION GUIDE
| This Patient Information has been approved by the U.S. Food and Drug Administration. Revised September 2025 | ||
PATIENT INFORMATION | ||
What is the most important information I should know about IBRANCE? IBRANCE may cause serious side effects, including: Low white blood cell counts (neutropenia). Low white blood cell counts are very common when taking IBRANCE and may cause serious infections that can lead to death. Your healthcare provider should check your white blood cell counts before and during treatment. If you develop low white blood cell counts during treatment with IBRANCE, your healthcare provider may stop your treatment, decrease your dose, or may tell you to wait to begin your treatment cycle. Tell your healthcare provider right away if you have signs and symptoms of low white blood cell counts or infections such as fever and chills. Lung problems (pneumonitis). IBRANCE may cause severe or life-threatening inflammation of the lungs during treatment that can lead to death. Tell your healthcare provider right away if you have any new or worsening symptoms, including:
Your healthcare provider may interrupt or stop treatment with IBRANCE completely if your symptoms are severe. See "What are the possible side effects of IBRANCE?" for more information about side effects. | ||
What is IBRANCE? IBRANCE is a prescription medicine used: In adults to treat hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread to other parts of the body (metastatic) in combination with:
In adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and with an abnormal phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) gene breast cancer that has spread to nearby tissue or lymph nodes (locally advanced), or to other parts of the body (metastatic) in combination with:
It is not known if IBRANCE is safe and effective in children. | ||
What should I tell my healthcare provider before taking IBRANCE? Before taking IBRANCE, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. IBRANCE and other medicines may affect each other causing side effects. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. | ||
How should I take IBRANCE?
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What are the possible side effects of IBRANCE? IBRANCE may cause serious side effects. See "What is the most important information I should know about IBRANCE?" The most common side effects of IBRANCE when used with either letrozole or fulvestrant include:
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The most common side effects of IBRANCE when used in combination with inavolisib plus fulvestrant include:
IBRANCE may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider about family planning options before starting IBRANCE if this is a concern for you. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of IBRANCE. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. | ||
How should I store IBRANCE?
Keep IBRANCE and all medicines out of the reach of children. | ||
General information about the safe and effective use of IBRANCE Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IBRANCE for a condition for which it was not prescribed. Do not give IBRANCE to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for more information about IBRANCE that is written for health professionals. | ||
What are the ingredients in IBRANCE? Active ingredient: palbociclib Inactive ingredients: microcrystalline cellulose, lactose monohydrate, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, and hard gelatin capsule shells. The light orange, light orange/caramel and caramel opaque capsule shells contain: gelatin, red iron oxide, yellow iron oxide, and titanium dioxide. The printing ink contains: shellac, titanium dioxide, ammonium hydroxide, propylene glycol, and simethicone. 
For more information, go to www.pfizer.com or call 1-800-438-1985. | ||
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