palbociclib

Action and Spectrum

Actions and Spectrum: 

The primary action of palbociclib is to slow down the progression of the cell cycle in cancer cells, preventing them from dividing and replicating. This inhibition of CDK4/6 activity leads to the arrest of cancer cells in the G1 phase of the cell cycle, a critical point in the cell cycle where cancer cells are most susceptible to chemotherapy and other treatments. 

Regarding its spectrum of activity, palbociclib is primarily used to treat hormone receptor-positive, HER2-negative breast cancer, which accounts for approximately 70% of all breast cancers. It is ineffective in treating hormone receptor-negative breast cancer or other types of cancer. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

WBC decreased 9 

Neutrophils decreased  

Neutropenia  

Platelets decreased  

Infections  

Neutropenia 

Neutrophils decreased 

AST increased  

ALT increased 

Leukopenia  

Fatigue  

Nausea  

WBC decreased 

Alopecia  

Stomatitis  

Diarrhea  

Anemia  

Leukopenia  

Rash  

Asthenia  

Vomiting  

Thrombocytopenia  

Dry skin  

Pyrexia   

1-10% 

Asthenia  

AST increased 

Dysgeusia  

Epistaxis  

Lacrimation increased  

Dry skin  

ALT increased  

Vision blurred  

Anemia 

AST increased 

Dry eye  

Infections 

Anemia 

Platelets decreased 

ALT increased 

Thrombocytopenia 

Fatigue 

Leukopenia 

Decreased appetite 

Vomiting 

Stomatitis 

Rash 

WBC decreased  

<1% 

Anemia 

Pyrexia 

Nausea 

Thrombocytopenia 

ALT increased 

Febrile neutropenia 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

• Pregnancy and breastfeeding: palbociclib can cause fetal harm and is contraindicated in pregnant women. It is also not recommended for use in breastfeeding women as it may be excreted in breast milk and can harm the nursing infant. 
• Liver impairment: palbociclib is metabolized in the liver, and patients with severe liver impairment may experience increased levels of the drug in their system, which can lead to adverse effects. The use of palbociclib in patients with severe liver impairment should be done with caution and careful monitoring. 
• Interactions with other medications: palbociclib may interact with other medications, including strong CYP3A inhibitors and inducers. These interactions can lead to an increased risk of adverse effects or decreased efficacy of palbociclib. 
• QT prolongation: palbociclib can cause QT prolongation, which is a condition that affects the electrical activity of the heart and can lead to arrhythmias. Palbociclib should be used with caution in patients with a history of QT prolongation or who are taking medications that can cause QT prolongation. 
• Neutropenia:  palbociclib can cause neutropenia, a type of white blood cell characterized by a low level of neutrophils. Patients taking palbociclib should monitor their blood counts regularly to detect any signs of neutropenia. 
• Age: palbociclib has not been studied in patients under the age of 18, and its safety and efficacy in this population have not been established. 
• Hypersensitivity: palbociclib can cause allergic reactions in some patients, and those with a known hypersensitivity to the drug or any of its components should not take it. 

Pregnancy / Lactation

Pregnancy consideration: The drug is toxic and unsafe for pregnant women and the developing fetus. It may cause fetal death or lower birth weight. 

Breastfeeding warnings: No data on the excretion of palbociclib in breast milk is available. Because of possible serious effects, women are advised to breastfeed three weeks after the last dose of palbociclib. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no affirmation of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a product in humans; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits. The drug is not for pregnant women. 
• Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

palbociclib is a small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). CDK4/6 are important cell cycle regulators and are involved in the progression of cells from the G1 phase to the S phase, where DNA replication occurs. In hormone receptor-positive breast cancer, CDK4/6 is frequently overexpressed, leading to cancer cells’ uncontrolled growth and proliferation. 

Pharmacodynamics: 

palbociclib binds to the ATP-binding site of CDK4/6, preventing their interaction with cyclin D1 and inhibiting the downstream signaling pathways that drive the cell cycle. it leads to cell cycle arrest in the G1 phase, reducing cell proliferation and ultimately slowing tumor growth. 

palbociclib’s effect on the cell cycle is selective for cells dependent on CDK4/6 activity for proliferation, such as hormone receptor-positive breast cancer cells. palbociclib does not affect normal cells that are not dependent on CDK4/6 activity. 

Pharmacokinetics: 

Absorption 

The bioavailability is 46% in the serum 

Peak plasma concentration is achieved in 6-12 hours 

The steady state is achieved in 8 days 

Distribution 

Protein bound is 85% 

The volume of distribution is 2583 L 

Metabolism 

Extensively metabolized, primarily by CYP3A and SULT2A1 

Elimination 

Half-life: 29 hr (patients with advanced breast cancer) 

Oral clearance: 63.1 L/hr 

Excretion: 74.1% feces (2.3% unchanged); 17.5% urine (6.9% unchanged) 

Adminstartion

Administration: 

• Take palbociclib at the same time each day. 
• Swallow the pill whole with a glass of water. Do not crush, chew, or break the pill. 
• If you miss a dose of palbociclib, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the next dose at your regular time. Do not take two doses of palbociclib at the same time. 
• Do not stop taking palbociclib without talking to your healthcare provider, even if you feel well. 
• palbociclib may interact with other medications, so it is important to tell your healthcare provider about all medications you are taking, including over-the-counter drugs, vitamins, and herbal supplements. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: palbociclib (Rx) 

Pronounced: pal-boe-SYE-klib 

Why do we use palbociclib? 

palbociclib is a medication used to treat certain types of breast cancer. It is a type of targeted therapy called a cyclin-dependent kinase (CDK) 4/6 inhibitor. 

In breast cancer, CDK 4/6 proteins promote the growth and division of cancer cells. Palbociclib works by blocking these proteins, slowing down or stopping cancer cell growth and division. It can help to slow the progression of breast cancer. 

palbociclib is usually used with other medications, such as hormone therapy, for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative. Clinical studies have shown this combination treatment to improve progression-free survival (the amount of time a patient lives without cancer getting worse).