Abemaciclib


Generic Medicine Info
Indications and Dosage
Oral
Hormone receptor positive, HER2-negative locally advanced carcinoma of breast, Hormone receptor positive, HER2-negative metastatic carcinoma of breast
Adult: In patient with disease progression following endocrine therapy in combination with fulvestrant, [and a gonadotropin releasing hormone agonist if pre- or perimenopausal]: 150 mg bid. As monotherapy in patient with disease progression following endocrine therapy or chemotherapy: 200 mg bid, continue dose until disease progression or unacceptable toxicity. In combination with aromatase inhibitor in postmenopausal women: 150 mg bid, continue dose until disease progression or unacceptable toxicity. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).
Special Patient Group
Patients taking strong CYP3A4 inhibitors: Reduce dose to 100 mg bid, further reduce to 50 mg bid according to individual safety or tolerability.
Hepatic Impairment
Severe (Child-Pugh class C): Reduce dosing frequency to once daily.
Administration
Tab: May be taken with or without food. Take at the same time each day. Swallow whole, do not chew/crush/split.
Contraindications
Pregnancy and lactation.
Special Precautions
Severe hepatic and renal impairment. Patients taking concomitant strong CYP3A4 inhibitors.
Adverse Reactions
Significant: Bone marrow suppression (e.g. anaemia, leukopenia, thrombocytopenia), diarrhoea, increased in ALT and AST, infections.
Blood and lymphatic system disorders: Lymphopaenia.
Eye disorders: Increased lacrimation.
Gastrointestinal disorders: Nausea, vomiting, abdominal pain, constipation, stomatitis.
General disorders and administration site conditions: Fatigue, pyrexia.
Metabolism and nutrition disorders: Decreased appetite, dehydration.
Musculoskeletal and connective tissue disorders: Arthralgia, muscular weakness.
Nervous system disorders: Dysgeusia, headache, dizziness.
Respiratory, thoracic and mediastinal disorders: Cough.
Skin and subcutaneous tissue disorders: Alopecia, pruritus, rash, dry skin.
Potentially Fatal: Interstitial lung disease, pneumonitis, neutropenia, venous thromboembolic events.
Patient Counseling Information
This drug may cause dizziness or fatigue, if affected, do not drive or operate machinery.
Monitoring Parameters
Evaluate pregnancy status and hepatitis B virus screening prior to initiation of therapy. Monitor CBC with differential and platelets at baseline, every 2 weeks for the 1st 2 months, monthly for the next 2 months, then as clinically indicated; ALT, AST, and serum bilirubin at baseline, every 2 weeks for the 1st 2 months, monthly for the next 2 months, then as clinically indicated. Monitor for signs and symptoms of diarrhoea, dehydration, interstitial lung disease, pneumonitis, venous thrombosis and pulmonary embolism.
Overdosage
Symptoms: Fatigue, diarrhoea. Management: Supportive treatment.
Drug Interactions
Increased plasma concentrations with strong CYP3A4 inhibitors (e.g. clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, posaconazole, voriconazole). Decreased plasma concentrations with the strong CYP3A4 inducer (e.g. carbamazepine, phenytoin, rifampicin).
Food Interaction
Decreased plasma concentrations with St. John’s wort. Increased plasma concentrations with grapefruit.
Action
Description: Abemaciclib is a potent and selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4 and CDK 6). It blocks retinoblastoma tumour suppressor protein phosphorylation and prevents progression through the cell cycle, resulting in arrest at the G1 phase.
Pharmacokinetics:
Absorption: Bioavailability: 45% (following 200 mg single oral dose). Time to peak plasma concentration: 8 hours (range: 4.1-24 hours).
Distribution: Volume of distribution: Approx 690.3 L. Plasma protein binding: Approx 96%.
Metabolism: Metabolised in the liver primarily by CYP3A4 and forms primary metabolite N-desethylabemaciclib (M2); hydroxyabemaciclib (M20), and hydroxy-N-desethylabemaciclib (M18) active metabolites; and oxidative metabolite (M1).
Excretion: Via faeces (approx 81%, as metabolites); urine (approx 3%). Elimination half-life: 18.3 hours.
Chemical Structure

Chemical Structure Image
Abemaciclib

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5983, Physostigmine. https://pubchem.ncbi.nlm.nih.gov/compound/Physostigmine. Accessed Aug. 26, 2021.

Storage
Store below 30°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
ATC Classification
L01EF03 - abemaciclib ; Belongs to the class of cyclin-dependent kinase (CDK) inhibitors. Used in the treatment of cancer.
References
Anon. Abemaciclib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/07/2021.

Anon. Abemaciclib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/07/2021.

Buckingham R (ed). Abemaciclib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/07/2021.

Joint Formulary Committee. Abemaciclib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/07/2021.

Verzenio Tablet (Eli Lilly and Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/07/2021.

Verzenios 50 mg Film-coated Tablets (Eli Lilly Nederland B.V.). MHRA. https://products.mhra.gov.uk. Accessed 06/07/2021.

Disclaimer: This information is independently developed by MIMS based on Abemaciclib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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