Abemaciclib

Abemaciclib is a Cyclin-Dependent Kinase (CDK4/6) inhibitor used to treat hormone receptor (HR)-positive, HER2-negative breast cancer. It may be used alone or in combination with endocrine therapies such as tamoxifen, aromatase inhibitors, or fulvestrant to slow the growth and spread of cancer cells.

Abemaciclib is indicated: In combination with endocrine therapy for adjuvant treatment of HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence. With an aromatase inhibitor as initial endocrine therapy for HR-positive, HER2-negative advanced or metastatic breast cancer. With fulvestrant after disease progression following endocrine therapy. As monotherapy for advanced or metastatic HR-positive, HER2-negative breast cancer after endocrine therapy and prior chemotherapy.

Protein Kinase Inhibitor

Cyclin-Dependent Kinase (CDK4/6) Inhibitor

Abemaciclib inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), preventing phosphorylation of the retinoblastoma (Rb) protein and blocking cell cycle progression, thereby reducing tumour cell proliferation.

Inhibits cyclin-dependent kinases (CDKs) 4 and 6 These kinases are activated upon binding to D cyclins and play a crucial role in signaling pathways, which lead to cell cycle progression and cellular proliferation In ER-positive breast cancer cells, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation

Adult Dose: Breast Cancer Indicated for HR+/HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy as either monotherapy or in combination with fulvestrant Also, indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with HR+/HER2- advanced or metastatic breast cancer Monotherapy 200 mg PO BID Continue until disease progression or unacceptable toxicity Combination therapy With aromatase inhibitor Abemaciclib: 150 mg PO BID PLUS Aromatase inhibitor: See Prescribing Information Continue until disease progression or unacceptable toxicity With fulvestrant Abemaciclib: 150 mg PO BID PLUS Fulvestrant: 500 mg IM on Days 1, 15, and 29, and then once monthly thereafter Continue until disease progression or unacceptable toxicity Hepatic impairment Mild or moderate (Child-Pugh A or B): No dose adjustment required Severe (Child-Pugh C): Reduce dosing frequency to once daily Renal Dose: Renal impairment Mild or moderate (CrCl 30-89 mL/min): No dose adjustment required Severe, ESRD, or dialysis: Not studied

May take with or without food Instruct patient to take dose at approximately the same time each day

If a dose is missed, take the next scheduled dose at the usual time. Do not take a double dose.

Abemaciclib may cause a range of common and serious side effects. The most frequently reported include: Diarrhoea Nausea Vomiting Fatigue Decreased appetite Abdominal pain Headache Cough Constipation Dizziness Fever (Pyrexia) Dry mouth Stomatitis (mouth sores) Hair loss (Alopecia) Taste changes (Dysgeusia) Joint pain (Arthralgia) Rash or itching Peripheral oedema (swelling of the hands or feet) Laboratory abnormalities may include: Decreased white blood cell (WBC) count Neutropenia (decreased neutrophil count) Decreased lymphocyte count Thrombocytopenia (decreased platelet count) Anaemia Increased serum creatinine Elevated liver enzymes (ALT and AST) Seek immediate medical attention if you develop severe diarrhoea, fever, signs of infection, difficulty breathing, unusual bleeding, or symptoms of a serious allergic reaction.

Special precautions should be taken while using Abemaciclib: Venous Thromboembolism (VTE): Abemaciclib may increase the risk of blood clots, including deep vein thrombosis (DVT), pulmonary embolism (PE), and other venous thromboembolic events. Seek immediate medical attention if you develop leg swelling, chest pain, sudden shortness of breath, or unexplained swelling. Hepatotoxicity: Elevations in liver enzymes (ALT and AST) have been reported. Liver function tests (LFTs) should be performed before starting treatment and monitored regularly during therapy. Neutropenia: Abemaciclib may reduce neutrophil and white blood cell counts, increasing the risk of serious infections. Regular complete blood count (CBC) monitoring is recommended. Febrile Neutropenia: Although uncommon, fever associated with severe neutropenia may occur and requires urgent medical evaluation. Diarrhoea: Diarrhoea is one of the most common adverse effects of Abemaciclib, particularly during the first month of treatment. Maintain adequate hydration, start antidiarrhoeal treatment as advised by your healthcare provider, and seek medical attention if diarrhoea becomes severe or persistent. Risk of Infection: Contact your healthcare provider immediately if you develop fever, sore throat, cough, or other signs of infection.

Contraindicated in patients with known hypersensitivity to Abemaciclib or any of its components.

Avoid ketoconazole and other strong CYP3A inhibitors. Avoid concomitant use with strong or moderate CYP3A inducers. Dose adjustment may be required with CYP3A inhibitors.

May be taken with or without food. Avoid grapefruit or grapefruit juice unless advised otherwise, as they may affect CYP3A metabolism.

Pregnancy There are no available human data informing the drug-associated risk Based on findings from animal studies and the mechanism of action, can cause fetal harm when administered to a pregnant woman In animal data, administration of abemaciclib during organogenesis was teratogenic and caused decreased fetal weight at maternal exposures that were similar to human clinical exposure based on AUC at the maximum recommended human dose Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment Advise females of reproductive potential to use effective contraception during treatment and for at least 3 weeks after the last dose Based on findings in animals, abemaciclib may impair fertility in males of reproductive potential Lactation Unknown if distributed in human breast milk Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking abemaciclib and for at least 3 weeks after the last dose

Breastfeeding is not recommended during treatment and for the recommended period after the last dose.

Safety and effectiveness have not been established in pediatric patients.

No overall differences in safety or effectiveness have been observed between elderly and younger adults.

Renal impairment Mild or moderate (CrCl 30-89 mL/min): No dose adjustment required Severe, ESRD, or dialysis: Not studied

There is no specific antidote. In case of overdose, provide supportive care and seek immediate medical attention.

Store below 30°C, protected from light and moisture. Keep out of the reach of children.

Generic Name: Abemaciclib Molecular Formula: C₂₇H₃₂F₂N₈ Drug Class: Cyclin-Dependent Kinase (CDK4/6) Inhibitor