Palbociclib

About Palbociclib

• On February 3, 2015, the U.S. Food and Drug Administration (FDA) approved palbociclib for use alongside letrozole in the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as the first line of endocrine-based therapy for their metastatic condition. 
• Following this, on February 19, 2016, the FDA granted approval for this medicine in combination with fulvestrant to treat women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer experiencing disease progression. 
• Lastly, on March 31, 2017, the FDA provided regular approval to manage HR-positive, HER2-negative advanced or metastatic breast cancer in conjunction with an aromatase inhibitor as the initial endocrine-based therapy in postmenopausal women.
• The mechanism of action of palbociclib revolves around its role as a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor. By selectively targeting CDK4/6 downstream of the estrogen receptor (ER), it regulates cell growth by inducing G1 arrest and impeding cell-cycle progression. 
• This inhibition of CDK4/6 activity not only halts cell progression at the G1 phase of tumor development but also curbs the proliferation of tumor cells and impedes tumor growth. 
• It is prescribed for treating hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is used in combination with an aromatase inhibitor as the initial endocrine-based therapy or with fulvestrant in patients experiencing disease progression following endocrine therapy.

Strength: 

Palbociclib capsules is available in strengths of 125 mg, 100 mg, and 75 mg. 

Recommended Dosage:

Palbociclib is offered in capsule form for self-administration. Adhere precisely to your doctor’s instructions when taking the medicine. Follow all guidelines provided on your prescription label and carefully review all medication guides or instruction sheets. 

• The recommended regimen involves taking a Palbociclib 125 mg capsule orally once daily for 21 consecutive days, followed by 7 days off treatment, completing a full cycle of 28 days. This capsules can be taken with or without food.
• When the medicine is administered alongside fulvestrant, the suggested dosage of fulvestrant is 500 mg given on Days 1, 15, and 29 of the treatment cycle, followed by once-monthly doses thereafter. It is advisable to advise patients to take their Palbociclib dose at roughly the same time every day. For detailed dosage instructions, please consult your healthcare profession. 
• No dose adjustment is needed for patients with mild or moderate hepatic impairment (Child-Pugh classes A and B). For severe hepatic impairment (Child-Pugh class C), the recommended dose is 75 mg once daily for 21 days followed by 7 days off, completing a 28-day cycle.

If a patient vomits or misses a dose, they should not take an extra dose. Instead, they should take the next prescribed dose at the usual time. This capsules should be swallowed whole and should not be chewed, crushed, or split before swallowing. Do not ingest capsule if they are broken, cracked, or damaged in any way.

Important:

Pre/perimenopausal women receiving this medicine and fulvestrant combination therapy should also undergo treatment with luteinizing hormone-releasing hormone (LHRH) agonists per current clinical practice. Men receiving the medicine and aromatase inhibitor combination therapy should consider LHRH agonist treatment based on prevailing clinical guidelines.

Monitor complete blood counts before starting the therapy, at the beginning of each cycle, and on Day 15 of the first 2 cycles. For patients experiencing Grade 1 or 2 neutropenia within the initial 6 cycles, conduct complete blood counts every 3 months thereafter, before each cycle. 

Drug Interaction: 

• Avoid using the medicine concurrently with strong CYP3A inhibitors; if unavoidable, decrease the dose. 
• Refrain from combining the medicine with strong CYP3A inducers. 
• Additionally, consider reducing the dosage of sensitive CYP3A4 substrates with narrow therapeutic indices when administered alongside Palbociclib.
• Patients should avoid consuming grapefruit products, as grapefruit may interact with the medication.

Warnings & Precaution:

• Neutropenia requires regular blood count monitoring before and during Palbociclib treatment. 
• Interstitial Lung Disease (ILD)/Pneumonitis can occur, leading to severe outcomes. 
• Patients should be closely monitored for pulmonary symptoms, with discontinuation of the medication if ILD/pneumonitis is suspected.
• It also presents a risk of embryo-fetal toxicity, necessitating effective contraception and patient awareness. 

Common Palbociclib Side Effects:

• Neutropenia
• Infections
• Leukopenia
• Fatigue
• Nausea
• Stomatitis
• Anemia
• Alopecia
• Diarrhea
• Thrombocytopenia
• Rash
• Vomiting
• Decreased appetite
• Asthenia
• Pyrexia

Use in Specific Population

• Palbociclib has been shown to potentially harm fetuses in animal studies and through its mechanism of action. It is advised that pregnant women avoid taking this medicine due to this risk. 
• Additionally, there is currently no information available about whether the medicine, is present in human milk or its effects on milk production and breastfed infants. As a precaution, lactating women are advised not to breastfeed during the treatment and for three weeks after the last dose to avoid potentially serious adverse reactions in infants.
• For females of reproductive age, it is recommended to use effective contraception during the treatment and for at least three weeks after the final dose to prevent fetal harm.
• Male patients with female partners of reproductive potential are also advised to use effective contraception during the treatment and for three months after the last dose due to the potential for genotoxicity.
• Regarding fertility, this medicine may impair fertility in males based on animal studies. However, the safety and effectiveness in pediatric patients have not been studied extensively.
• No significant differences in safety or effectiveness were observed in pediatric patients compared to younger ones. Furthermore, dosage adjustment is not required in patients with mild, moderate, or severe renal impairment. 
• However, depending on the severity of hepatic impairment, dosage adjustments may be recommended by the doctor. Patients need to consult their healthcare provider for personalized advice and more information.

Storage and Handling 

• Store the capsules within a temperature range of 20°C to 25°C (68°F to 77°F) with excursions allowed between 15°C and 30°C (59°F and 86°F). 
• Properly dispose of any medication that has expired or is no longer required. 
• Keep the medicine away from pets and children.