Palbociclib is a medication used in the treatment of certain types of breast cancer. It is an oral targeted therapy that belongs to a class of drugs called cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Palbociclib is typically used in combination with other medications for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR-positive, HER2-negative) advanced or metastatic breast cancer.
The main purpose of palbociclib is to inhibit specific enzymes called cyclin-dependent kinases 4 and 6, which play a role in cell division and cancer growth. By blocking these enzymes, palbociclib can slow down the progression of cancer cells and prevent their proliferation.
Palbociclib is usually prescribed in combination with an aromatase inhibitor (such as letrozole or anastrozole) for postmenopausal women or with fulvestrant for both pre- and postmenopausal women. These combinations have been shown to improve progression-free survival in women with advanced or metastatic breast cancer.
Palbociclib (Ibrance) Uses:
- Advanced Breast Cancer (initial endocrine-based therapy):
- Treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer (in combination with an aromatase inhibitor) in postmenopausal females or in adult males as initial endocrine-based therapy.
- Advanced Breast Cancer (with disease progression following endocrine therapy):
- Treatment of HR-positive, HER2-negative advanced or metastatic breast cancer (in combination with fulvestrant) in adult patients with disease progression after endocrine therapy.
Palbociclib (Ibrance) Dose in Adults
Palbociclib (Ibrance) Dose in the treatment of Advanced Breast cancer, initial endocrine-based therapy:
- The recommended dose of palbociclib in HER2-negative advanced breast cancer is 125 mg taken orally once daily for 21 days, followed by a break of 7 days.
- This 28-day cycle is repeated until the disease progresses or side effects become too severe.
- Palbociclib is typically used in combination with an aromatase inhibitor, which is a type of hormone therapy.
- This combination has been shown to be effective in treating advanced breast cancer.
- For males who are receiving palbociclib along with an aromatase inhibitor, it is also recommended to consider treatment with an LHRH agonist, which helps suppress hormone production.
Palbociclib (Ibrance) Dose in the treatment of Advanced Breast cancer (with disease progression following endocrine therapy):
- In the treatment of advanced breast cancer with disease progression following endocrine therapy, the recommended dose of palbociclib is 125 mg taken orally once daily for 21 days, followed by a break of 7 days.
- This 28-day cycle is repeated until the disease progresses or side effects become too severe.
- Palbociclib is used in combination with fulvestrant, which is another type of hormone therapy.
- For pre- or perimenopausal females receiving palbociclib in combination with fulvestrant, it is also suggested to consider treatment with an LHRH/GnRH agonist, such as goserelin. These agonists help suppress hormone production
Missed/vomited doses:
- If a dose of palbociclib is missed or vomited, it is not recommended to take an additional dose on the same day.
- Instead, the dosing should be resumed with the next scheduled daily dose.
Dosage adjustment for concomitant therapy:
- Strong CYP3A Inhibitors:
- It is generally recommended to avoid using strong CYP3A inhibitors simultaneously with palbociclib.
- However, if coadministration cannot be avoided, the palbociclib dose should be reduced to 75 mg taken orally once daily.
- Strong CYP3A inhibitors are medications that can significantly inhibit the activity of the CYP3A enzyme system in the liver, affecting the metabolism of palbociclib.
- Once the strong inhibitor is discontinued, the palbociclib dose should be increased (after 3 to 5 half-lives of the inhibitor have passed) back to the dose used before starting the strong CYP3A inhibitor.
- CYP3A Inducers:
- It is advised to avoid concomitant use of strong CYP3A inducers with palbociclib.
- Strong CYP3A inducers are medications that can enhance the activity of the CYP3A enzyme system, potentially reducing the effectiveness of palbociclib.
Use in Children:
Not indicated
Palbociclib (Ibrance) Pregnancy Risk Category: N (not assigned)
- Palbociclib has the potential to cause harm to the fetus if used during pregnancy, based on its mechanism of action and findings from animal reproduction studies.
- Therefore, it is crucial to assess the pregnancy status of females of reproductive potential before starting palbociclib treatment.
- For females of reproductive potential who are receiving palbociclib, it is strongly advised to use effective contraception during the treatment period.
- Additionally, contraception should be continued for at least 3 weeks after the last dose of palbociclib.
- In the case of males who have female partners of reproductive potential, they should also use effective contraception while receiving palbociclib.
- It is recommended to continue contraception for a period of 3 months after the last dose of the medication.
- Animal toxicology studies have shown adverse effects on male reproductive function and fertility with palbociclib.
- Therefore, males of reproductive potential may want to consider sperm preservation before starting palbociclib therapy.
Use of palbociclib during breastfeeding
- The presence of palbociclib in breast milk is not known.
- Since there is a potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during palbociclib treatment and for at least 3 weeks after the last dose.
Palbociclib (Ibrance) Dose in Kidney Disease:
- CrCl (Creatinine Clearance) >15 mL/minute:
- No dosage adjustment is necessary for patients with a creatinine clearance greater than 15 mL/minute.
- CrCl ≤15 mL/minute:
- The manufacturer's labeling does not provide specific dosage adjustments for patients with a creatinine clearance of 15 mL/minute or less.
- This means that there is no established dosing recommendation based on studies in patients with severe renal impairment.
- Caution should be exercised when considering palbociclib in this population, and the potential benefits and risks should be evaluated on an individual basis.
- Hemodialysis:
- The manufacturer's labeling does not provide specific dosage adjustments for patients undergoing hemodialysis.
- Since palbociclib has not been studied in patients undergoing hemodialysis, there is limited information available to guide dosing recommendations for this population.
Palbociclib (Ibrance) Dose in Liver disease:
- Mild or moderate impairment (Child-Pugh classes A and B):
- No dosage adjustment is necessary for patients with mild or moderate hepatic impairment.
- This suggests that the standard recommended dosage can be used in these patients.
- Severe impairment (Child-Pugh class C):
- In patients with severe hepatic impairment (Child-Pugh class C), the palbociclib dose should be reduced to 75 mg once daily for 21 days, followed by a break of 7 days.
- This 28-day cycle should be repeated.
- The dosage reduction is recommended in this population due to the decreased ability of the liver to metabolize the medication.
Common Side Effects of Palbociclib (Ibrance):
- Central Nervous System:
- Fatigue
- Dermatologic:
- Alopecia
- Skin Rash
- Xeroderma
- Gastrointestinal:
- Nausea
- Stomatitis
- Diarrhea
- Vomiting
- Decreased Appetite
- Hematologic & Oncologic:
- Neutropenia
- Anemia
- Leukopenia
- Thrombocytopenia
- Hepatic:
- Increased Serum Aspartate Aminotransferase
- Increased Serum Alanine Aminotransferase
- Infection:
- Infection
- Neuromuscular & Skeletal:
- Asthenia
- Miscellaneous:
- Fever
Less Common Side Effects Of Palbociclib (Ibrance):
- Gastrointestinal:
- Dysgeusia
- Hematologic & Oncologic:
- Febrile Neutropenia
- Ophthalmic:
- Blurred Vision
- Increased Lacrimation
- Dry Eye Syndrome
- Respiratory:
- Epistaxis
Contraindications to Palbociclib (Ibrance):
In the United States, the manufacturer's labeling for palbociclib does not list any specific contraindications. This means that there are no absolute reasons stated in the labeling that would prevent the use of palbociclib in certain patients.
In the Canadian labeling, it specifies that hypersensitivity to palbociclib or any component of the formulation is a contraindication. This means that if a patient has a known hypersensitivity or allergic reaction to palbociclib or any ingredient in the formulation, the medication should not be used.
Warnings and precautions
Suppression of bone marrow
- Bone marrow suppression, a potential side effect of palbociclib, can cause low levels of certain blood cells.
- Neutropenia, which is a decrease in a type of white blood cell called neutrophils, was frequently seen in studies, including more severe cases.
- Neutropenia typically occurred about 15 days after starting treatment and lasted for around 7 days when severe.
- Other blood-related effects like low white blood cell count, red blood cell count, lymphocyte count, and platelet count, as well as neutropenic fever and sepsis, were also reported.
- Regular blood tests should be done before starting palbociclib and at the beginning of each treatment cycle to monitor for these effects.
- If neutropenia is mild in the first 6 cycles, monitoring can be done every 3 months.
- If severe neutropenia occurs, treatment may be interrupted, delayed, or the dose may be reduced.
Toxicity to the GI:
- In clinical studies, some patients experienced gastrointestinal (GI) toxicity when taking palbociclib.
- This included symptoms like nausea, vomiting, diarrhea, and stomatitis (inflammation of the mouth).
- These GI side effects were generally mild to moderate, with most cases being classified as grade 1 or 2.
Infection
- Patients receiving palbociclib in combination with an antiestrogen medication may have a higher risk of developing infections, including more severe cases (grades 3 and 4), compared to those receiving only an antiestrogen.
- It is important to be vigilant and monitor for any signs or symptoms of infection while on palbociclib treatment.
- If any signs of infection are noticed, it is essential to seek medical attention promptly for appropriate evaluation and management.
- Your healthcare provider will guide you on how to manage and treat infections effectively.
Hepatic impairment
- Patients with severe hepatic impairment, which refers to significant liver damage or dysfunction, are recommended to receive a reduced dose of palbociclib.
- The adjustment is necessary because the liver plays a crucial role in metabolizing medications, and severe impairment can affect the body's ability to process palbociclib effectively.
- By reducing the dose, the aim is to ensure the medication is safely and appropriately utilized in patients with compromised liver function.
Palbociclib (Ibrance): Drug Interaction
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Palbociclib Drug Interactions: Category C Drugs (Monitor Therapy) |
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The blood levels of palbociclib may increase with these drugs |
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The blood levels of palbociclib may decrease with these drugs |
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Palbociclib may increase the blood levels of these drugs |
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The risk of bone marrow suppression may increase |
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The effects of these drugs may diminish |
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The diagnostic efficacy of these tests may diminish |
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Palbociclib Drug Interactions: Category D drugs (Avoid if possible) |
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The blood levels of palbociclib may increase with these drugs |
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The blood levels of palbociclib may decrease with these drugs |
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Palbociclib may increase the blood levels of these drugs |
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The risk of bone marrow suppression may increase |
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The effects of these drugs may diminish |
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Palbociclib Drug Interactions: Category X Drugs (Contraindicated) |
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The blood levels of palbociclib may increase with these drugs |
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The blood levels of palbociclib may decrease with these drugs |
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The risk of bone marrow suppression may increase |
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The effects of these drugs may diminish |
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Monitoring parameters:
Complete Blood Count (CBC) with differential:
- Before starting treatment, every 2 weeks for the first 2 cycles, and then before each cycle of treatment.
- Additional monitoring should be done as clinically indicated.
- If neutropenia (low neutrophil count) remains mild (grades 1 or 2) during the first 6 cycles, monitoring can be extended to every 3 months before subsequent cycles and as needed based on clinical judgment.
Pregnancy test:
- Prior to starting treatment, females of reproductive potential should undergo a pregnancy test to determine if they are pregnant.
- This is important because palbociclib may cause harm to the developing fetus if used during pregnancy.
Signs/symptoms of infection:
- Be vigilant for any signs or symptoms of infection, such as fever, chills, sore throat, or any other unusual symptoms.
- If any indications of infection arise, seek medical attention promptly for appropriate evaluation and management.
Adherence monitoring:
- It is crucial to monitor and ensure that patients are taking palbociclib as prescribed by their healthcare provider.
- Adherence to the prescribed regimen is important for the medication to be effective.
How to administer Palbociclib (Ibrance)?
Administer with food:
- Take palbociclib with a meal or snack.
- This helps with absorption and reduces the chance of stomach upset.
Take at the same time each day:
- Try to take palbociclib at around the same time every day.
- This helps maintain a consistent level of the medication in your body.
Swallow the capsules whole:
- Do not crush, chew, or open the capsules before swallowing them.
- Take the capsules with a glass of water.
- It's important to swallow them whole to ensure the proper release and absorption of the medication.
Check the capsules:
- Before taking palbociclib, make sure the capsules are not broken, cracked, or damaged in any way.
- If you notice any damage or if the capsules are not fully intact, do not ingest them.
Mechanism of action of Palbociclib (Ibrance):
- Palbociclib is a type of medication that inhibits specific enzymes called cyclin-dependent kinases (CDKs), specifically CDK4 and CDK6.
- CDKs play a crucial role in regulating the progression of cells through the different phases of the cell cycle, particularly the G1/S phase transition.
- By inhibiting CDKs, palbociclib prevents the hyperphosphorylation of a protein called retinoblastoma (Rb), which is involved in controlling cell growth.
- This inhibition of CDKs and Rb phosphorylation helps to reduce the proliferation (growth and division) of breast cancer cells by blocking their transition from the G1 to the S phase of the cell cycle.
- When palbociclib is used in combination with an antiestrogen medication, it leads to increased inhibition of Rb phosphorylation, signaling pathways downstream of CDKs, and ultimately tumor growth, compared to using each medication alone.
- This combination therapy has shown promising results in the treatment of breast cancer.
Absorption:
- The absorption of palbociclib is increased when taken with high-fat, high-calorie food.
Distribution:
- The volume of distribution (V) of palbociclib is approximately 2,583 liters, indicating that it distributes widely throughout the body.
Protein binding:
- Palbociclib is highly bound to proteins in the blood, with an approximate binding rate of 85%.
Metabolism:
- Palbociclib undergoes extensive metabolism in the liver.
- The main metabolic pathways involve oxidation and sulfonation, primarily mediated by enzymes called CYP3A and sulfotransferase (SULT) enzyme SULT2A1, respectively.
- Minor metabolic pathways include acylation and glucuronidation.
Bioavailability:
- The mean absolute bioavailability of palbociclib is approximately 46%, indicating the fraction of the administered dose that reaches the systemic circulation unchanged.
Half-life elimination:
- The half-life of palbociclib elimination is approximately 29 ± 5 hours.
- This means it takes about 29 hours for the concentration of palbociclib in the body to decrease by half.
Time to peak:
- Palbociclib reaches its peak concentration in the blood between 6 to 12 hours after administration.
Excretion:
- Palbociclib is primarily excreted in the feces (approximately 74%) as metabolites.
- A smaller portion is excreted in the urine (approximately 18%), also primarily as metabolites.
International Brand Names of Palbociclib:
- Ibrance
Palbociclib Brands Names in Pakistan:
No Brands Available in Pakistan.
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