Oral Hormone receptor positive, HER2-negative locally advanced carcinoma of breast, Hormone receptor positive, HER2-negative metastatic carcinoma of breast
Adult: In combination with aromatase inhibitor, or in combination with fulvestrant in women who have received prior endocrine therapy: 125 mg once daily for 21 days, followed by 7 days off, repeat every 28 days until disease progression or unacceptable toxicity. Pre/perimenopausal women should be treated with luteinising hormone-releasing hormone (LHRH) agonists prior to initiation of treatment and continued throughout the duration of treatment. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline). Recommended dose reduction: 1st reduction: 100 mg once daily; 2nd reduction: 75 mg once daily; discontinue if dose reduction below 75 mg once daily is required.
Special Patient Group
Patient taking potent CYP3A inhibitors: Reduce dose to 75 mg once daily for 21 days, followed by 7 days off, repeat every 28 days.
Hepatic Impairment
Severe: Reduce dose to 75 mg once daily for 21 days, followed by 7 days off, repeat every 28 days.
Administration
hard capsule: Should be taken with food. Take at the same time each day. Swallow whole, do not chew/crush/open. Avoid grapefruit products.
Contraindications
Pregnancy and lactation.
Special Precautions
Hepatic impairment.
Adverse Reactions
Significant: Bone marrow suppression (e.g. neutropenia, leucopenia, anaemia, thrombocytopenia), infection, diarrhoea, nausea, stomatitis, vomiting. Eye disorders: Blurred vision, increased lacrimation, dry eye. Gastrointestinal disorders: Dysgeusia. General disorders and administration site conditions: Fatigue, asthenia, pyrexia. Investigations: Increased ALT/AST. Metabolism and nutrition disorders: Decreased appetite. Respiratory, thoracic and mediastinal disorders: Epistaxis. Skin and subcutaneous tissue disorders: Alopecia, rash, dry skin.
Patient Counseling Information
This drug may cause fatigue, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor CBC with differential prior to treatment initiation, every 2 weeks for the 1st 2 cycles, then prior to each cycle, and as clinically indicated. Perform pregnancy test prior to initiation of therapy. Monitor signs and symptoms of infection and pulmonary embolism.
Increased plasma concentration and systemic exposure with strong CYP3A inhibitors (e.g. clarithromycin, telithromycin, itraconazole, ketoconazole, posaconazole, voriconazole, indinavir, ritonavir, ritonavir-boosted lopinavir, nelfinavir, saquinavir, telaprevir, nefazodone, verapamil). Decreased plasma concentration with moderate CYP3A inducers (e.g. bosentan, efavirenz, etravirine, modafinil, nafcillin) or strong CYP3A inducers (e.g. carbamazepine, phenytoin, enzalutamide, rifampicin). May increase the plasma concentration of CYP3A substrates (e.g. ciclosporin, everolimus, sirolimus, tacrolimus, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine).
Food Interaction
Increased exposure with grapefruit or grapefruit juice. Decreased exposure with St John’s wort.
Action
Description: Palbociclib is a reversible, selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. Cyclin D1, CDK 4 and 6 are downstream of multiple signalling pathways which lead to cellular proliferation. Inhibition of CDK4/6 reduces proliferation of breast cancer cell lines by blocking progression from G1 into S phase of the cell cycle. Pharmacokinetics: Absorption: Increased with high fat and high calorie food. Time to peak plasma concentration: Approx 6-12 hours. Distribution: Volume of distribution: Approx 2,583 L. Plasma protein binding: Approx 85%. Metabolism: Metabolised in the liver by CYP3A and sulfotransferase (SULT) enzyme 2A1, primarily via oxidation and sulfonation, with acylation and glucuronidation contributing as minor pathway. Excretion: Mainly via faeces (approx 74%, mainly as metabolites); urine (approx 18%, mainly as metabolites). Elimination half-life: Approx 29 hours.
Chemical Structure
Palbociclib Source: National Center for Biotechnology Information. PubChem Database. Palbociclib, CID=5330286, https://pubchem.ncbi.nlm.nih.gov/compound/Palbociclib (accessed on Jan. 22, 2020)
Storage
Store between 20-25°C.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01EF01 - palbociclib ; Belongs to the class of cyclin-dependent kinase (CDK) inhibitors. Used in the treatment of cancer.
References
Anon. Palbociclib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 28/03/2018.Anon. Palbociclib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 28/03/2018.Buckingham R (ed). Palbociclib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/03/2018.Ibrance Capsule (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/03/2018.Joint Formulary Committee. Palbociclib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/03/2018.Palbociclib. Drugs and Lactation Database (LactMed) [Internet]. Bethesda, MD. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK501922/. Accessed 03/04/2018.
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