Palbociclib

Patients taking strong CYP3A inhibitors: Reduce dose to 75 mg once daily.

Severe (Child-Pugh class C): Reduce dose to 75 mg once daily for 21 days, followed by 7 days off therapy to complete a 28-day cycle.

Palbociclib cap: Should be taken with food. Swallow whole & do not crush/open. Avoid grapefruit or grapefruit juice.
Palbociclib tab: May be taken with or without food. Swallow whole & do not chew/crush/split. Avoid grapefruit or grapefruit juice.

Pregnancy and lactation.

Moderate to severe hepatic and renal impairment. Concomitant use with strong CYP3A inhibitors.

Significant: Haematological disorders (e.g. neutropenia, febrile neutropenia, leucopenia, anaemia, thrombocytopenia); infections; venous thromboembolic events (e.g. DVT, pulmonary embolism).
Eye disorders: Blurred vision, increased lacrimation, dry eye.
Gastrointestinal disorders: Diarrhoea, nausea, vomiting, stomatitis, dysgeusia.
General disorders and administration site conditions: Fatigue, asthenia, pyrexia.
Investigations: Increased ALT and AST.
Metabolism and nutrition disorders: Decreased appetite.
Respiratory, thoracic and mediastinal disorders: Epistaxis.
Skin and subcutaneous tissue disorders: Rash, alopecia, dry skin, palmar-plantar erythrodysaesthesia syndrome.
Potentially Fatal: Interstitial lung disease (ILD) and/or pneumonitis; neutropenic sepsis.

Women of childbearing potential who are receiving the therapy and their male partners must use proven birth control methods during treatment and for at least 3 weeks (in women) or 14 weeks (in men) after stopping the treatment.

Perform pregnancy test in women of childbearing potential prior to the start of treatment. Obtain CBC with differential prior to therapy initiation, every 2 weeks for 1st 2 cycles, at the beginning of each cycle, and as clinically indicated. Hepatitis B virus screening with HBsAg, hepatitis B core antibody, total Ig or IgG, and antibody to HBsAg is recommended before or at the beginning of systemic chemotherapy. Perform a comprehensive CV assessment and screening for CV disease risk factors prior to initiation of therapy. Closely monitor for signs and symptoms of venous thromboembolism, ILD, pneumonitis, haematologic toxicity, and infections.

Symptoms: Nausea, vomiting, and neutropenia. Management: Supportive treatment.

May result in decreased exposure and consequently a risk for lack of efficacy with strong CYP3A inducers (e.g. rifampicin, phenytoin, carbamazepine, enzalutamide). Increased exposure and plasma concentration with strong CYP3A inhibitors (e.g. itraconazole, ketoconazole, clarithromycin, lopinavir, ritonavir, indinavir, nefazodone, telaprevir, telithromycin). May increase the exposure of sensitive CYP3A4 substrates with a narrow therapeutic index (e.g. midazolam, fentanyl, alfentanil, quinidine, pimozide, ciclosporin, ergotamine). Concomitant use of palbociclib cap with rabeprazole (under fasted conditions) may result in significantly decreased palbociclib exposure and concentration.

Absorption and exposure are very low when given without food (cap). Tab/cap: Increased systemic exposure and concentration with food (particularly with high-fat and high-calorie meals) compared to when given under fasted conditions. May increase the exposure and plasma concentration with grapefruit or grapefruit juice. May decrease the exposure and plasma serum concentration with St. John's wort.

Description:
Mechanism of Action: Palbociclib is a highly selective and reversible cyclin-dependent kinase (CDK) 4 and 6 inhibitor. CDKs are involved in regulating the progression of the tumour cell cycle at the G1/S phase by blocking the retinoblastoma hyperphosphorylation. Palbociclib reduces the proliferation of breast cancer cell lines by inhibiting the progression from G1 into S phase of the cell cycle.
Pharmacokinetics:
Absorption: Food, particularly high-fat and high-calorie meals, increases exposure and concentration of tab/cap. Absolute bioavailability: 46%. Time to peak plasma concentration: 4-12 hours (tab); 6-12 hours (cap).
Distribution: Volume of distribution: 2,583 L. Plasma protein binding: Approx 85%.
Metabolism: Extensively metabolised in the liver via oxidation and sulfonation (major pathways) primarily by CYP3A isoenzyme and sulfotransferase (SULT) enzyme SULT2A1; acylation and glucuronidation also contribute as minor metabolic pathways.
Excretion: Mainly via faeces (approx 75%, primarily as metabolites); urine (approx 18%, primarily as metabolites). Elimination half-life: 29 hours ± 5 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5330286, Palbociclib. https://pubchem.ncbi.nlm.nih.gov/compound/Palbociclib. Accessed June 25, 2024.

Store between 15-30°C. Protect the tab from moisture.

Targeted Cancer Therapy

L01EF01 - palbociclib ; Belongs to the class of cyclin-dependent kinase (CDK) inhibitors. Used in the treatment of cancer.

Gervaso L, Montero AJ, Jia X et al. Venous Thromboembolism in Breast Cancer Patients Receiving Cyclin‐dependent Kinase Inhibitors. J Thromb Haemost. 2020;18:162-168. doi: 10.1111/jth.14630. Accessed 21/05/2024. PMID: 31479568

Thein KZ, Htut T, Ball S et al. Venous Thromboembolism Risk in Patients with Hormone Receptor-positive HER2 negative Metastatic Breast Cancer Treated with Combined CDK 4/6 Inhibitors Plus Endocrine Therapy Versus Endocrine Therapy Alone: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Breast Cancer Research and Treatment. 2020. https://doi.org/10.1007/s10549-020-05783-3. Accessed 21/05/2024. PMID: 32647939

West MT, Smith C, Kaempf A et al. CDK 4/6 Inhibitors are Associated with a High Incidence of Thrombotic Events in Women with Breast Cancer in Real-world Practice. Eur J Haematol. 2021;106(5):634-642. doi: 10.1111/ejh.13590. Accessed 21/05/2024. PMID: 33527479

Anon. Palbociclib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/05/2024.

Buckingham R (ed). Palbociclib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/05/2024.

Ibrance Capsule (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/05/2024.

Ibrance Hard Capsules and Film-coated Tablets (Pfizer Europe MA EEIG). European Medicines Agency [online]. Accessed 21/05/2024.

Ibrance Tablet, Film Coated (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/05/2024.

Ibrance Tablets 75 mg, 100 mg, and 125 mg (Pfizer [Malaysia] Sdn. Bhd.). https://www.npra.gov.my. Accessed 21/05/2024.

Joint Formulary Committee. Palbociclib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/05/2024.

Palbociclib. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 21/05/2024.

Palbociclib. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 08/05/2024.

Pfizer New Zealand Limited. Ibrance 75 mg, 100 mg, and 125 mg Capsules/Tablets data sheet 4 May 2023. Medsafe. http://www.medsafe.govt.nz. Accessed 08/05/2024.