Alectinib


Generic Medicine Info
Indications and Dosage
Oral
Anaplastic lymphoma kinase-positive advanced non-small cell lung cancer
Adult: As monotherapy: As 1st-line treatment or in patients who have previously been treated with crizotinib: 600 mg bid; continue 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).
Hepatic Impairment
Severe (Child-Pugh class C): 450 mg bid.
Administration
Should be taken with food. Swallow whole w/ water, do not open or dissolve the contents of cap.
Contraindications
Pregnancy and lactation.
Special Precautions
Patient with increased risk for gastrointestinal perforation (e.g. history of diverticulitis, metastases to the gastrointestinal tract). Severe hepatic impairment (Child-Pugh class C).
Adverse Reactions
Significant: Haemolytic anaemia (including cases associated with a negative direct antiglobulin test); hepatotoxicity (e.g. LFT abnormalities [including increased AST, ALT, bilirubin], drug-induced liver injury); myalgia or musculoskeletal pain, increased creatine phosphokinase; interstitial lung disease, pneumonitis, photosensitivity, bradycardia, gastrointestinal perforation.
Blood and lymphatic system disorders: Anaemia, lymphocytopenia.
Eye disorders: Vision disorders.
Gastrointestinal disorders: Constipation, nausea, diarrhoea, vomiting, stomatitis, dysgeusia.
General disorders and administration site conditions: Oedema, fatigue.
Investigations: Increased weight, serum alkaline phosphatase or serum creatinine.
Musculoskeletal and connective tissue disorders: Back pain.
Nervous system disorders: Headache.
Renal and urinary disorders: Acute kidney injury.
Skin and subcutaneous tissue disorders: Rash.
Potentially Fatal: Severe renal impairment.
Patient Counseling Information
This drug may cause symptomatic bradycardia (e.g. syncope, dizziness, hypotension) or vision disorders, if affected, do not drive or operate machinery. Avoid prolonged sun exposure during and for at least 7 days after stopping treatment. Use broad-spectrum sunscreen and lip balm.
Monitoring Parameters
Test for the presence of abnormal ALK positivity in tumour tissue or plasma specimens prior to initiation of therapy. Obtain LFTs (e.g. ALT, AST, total bilirubin) at baseline and every 2 weeks during the 1st 3 months of therapy, then monthly and as clinically necessary (monitor more frequently in patients who develop transaminase and bilirubin elevations); creatine phosphokinase levels every 2 weeks for the 1st month of therapy, then as clinically indicated. Monitor heart rate and blood pressure; signs and symptoms of haemolytic anaemia, gastrointestinal perforations, interstitial lung disease, pneumonitis, and myalgia.
Drug Interactions
May increase plasma concentration of P-glycoprotein (P-gp) substrates (e.g. lapatinib, nilotinib, everolimus, sirolimus, topotecan, dabigatran etexilate, digoxin) or Breast Cancer Resistance Protein (BCRP) substrates (e.g. mitoxantrone, methotrexate). Concurrent use with strong CYP3A inducers (e.g. rifampicin, rifabutin, phenobarbital, phenytoin, carbamazepine) may decrease the plasma concentration of alectinib. Concomitant use with strong CYP3A inhibitors (e.g. posaconazole, voriconazole, itraconazole, ketoconazole, telithromycin, ritonavir, saquinavir, nefazodone) may increase the exposure to alectinib. Increased risk for gastrointestinal perforation with drugs that have recognised risk of gastrointestinal perforation.
Food Interaction
Increased exposure by approx threefold with a high-fat, high-calorie meal.
Action
Description:
Mechanism of Action: Alectinib is a potent and highly selective inhibitor of anaplastic lymphoma kinase (ALK) and rearranged during transfection (RET) tyrosine kinase. It inhibits ALK phosphorylation and ALK-mediated activation of the downstream signalling proteins (STAT3 and AKT), leading to decreased viability of tumour cells in multiple cell lines harbouring ALK fusions, amplifications or activating mutations.
Pharmacokinetics:
Absorption: Increased exposure by approx threefold with a high-fat, high-calorie meal. Bioavailability: 37% (under fed conditions). Time to peak plasma concentration: Approx 4-6 hours.
Distribution: Volume of distribution: 4,016 L (alectinib); 10,093 L (M4, active metabolite). Plasma protein binding: >99%.
Metabolism: Metabolised in the liver by CYP3A4 into M4 (major active metabolite); subsequently, M4 is also metabolised by CYP3A4.
Excretion: Via faeces (98%; 84% as unchanged parent drug, 6% as M4); urine (<0.5%). Elimination half-life: 33 hours (alectinib); 31 hours (M4).
Chemical Structure

Chemical Structure Image
Alectinib

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 49806720, Alectinib. https://pubchem.ncbi.nlm.nih.gov/compound/Alectinib. Accessed Nov. 25, 2021.

Storage
Store below 30°C. Protect from light and moisture. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
MIMS Class
Targeted Cancer Therapy
ATC Classification
L01ED03 - alectinib ; Belongs to the class of anaplastic lymphoma kinase (ALK) inhibitors. Used in the treatment of cancer.
References
Alecensa 150 mg Hard Capsules (Roche [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 12/10/2021.

Alecensa 150 mg Hard Capsules (Roche Products Limited). MHRA. https://products.mhra.gov.uk. Accessed 30/09/2021.

Alecensa Capsules (Genentech USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 30/09/2021.

Anon. Alectinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 30/09/2021.

Anon. Alectinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 30/09/2021.

Buckingham R (ed). Alectinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/09/2021.

Joint Formulary Committee. Alectinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/09/2021.

Roche Products (New Zealand) Limited. Alecensa 150 mg Hard Capsules data sheet 15 March 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 30/09/2021.

Disclaimer: This information is independently developed by MIMS based on Alectinib 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 © 2024 MIMS. All rights reserved. Powered by MIMS.com
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