Alectinib

Oral
Anaplastic lymphoma kinase-positive advanced non-small cell lung cancer

Severe (Child-Pugh class C): 450 mg bid.

Should be taken with food. Swallow whole w/ water, do not open or dissolve the contents of cap.

Pregnancy and lactation.

Patient with increased risk for gastrointestinal perforation (e.g. history of diverticulitis, metastases to the gastrointestinal tract). Severe hepatic impairment (Child-Pugh class C).

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.

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.

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.

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.

Increased exposure by approx threefold with a high-fat, high-calorie meal.

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).

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.

Store below 30°C. Protect from light and moisture. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

Targeted Cancer Therapy

L01ED03 - alectinib ; Belongs to the class of anaplastic lymphoma kinase (ALK) inhibitors. Used in the treatment of cancer.

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.