Brigatinib


Generic Medicine Info
Indications and Dosage
Oral
Anaplastic lymphoma kinase-positive advanced non-small cell lung cancer
Adult: As monotherapy in patients previously not treated with an anaplastic lymphoma kinase (ALK) inhibitor or previously treated with crizotinib: Initially, 90 mg once daily for 7 days, then increase to 180 mg once daily if tolerated. Continue until disease progression or unacceptable toxicity occurs. If treatment is interrupted for 14 days or longer for reasons other than adverse effects, resume treatment at 90 mg once daily for 7 days before increasing to the previously tolerated dose. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Special Patient Group
Patients taking moderate CYP3A4 inhibitors: Reduce dose by approx 40%. Refer to detailed product guideline.

Patients taking strong CYP3A4 inhibitors: Reduce dose by approx 50%. Refer to detailed product guideline.

Patients taking moderate CYP3A4 inducers: Increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose as tolerated, up to Max of twice the dose. Refer to detailed product guideline.
Renal Impairment
CrCl (mL/min) Dosage
15-29 Reduce dose by approx 50% (i.e. from 180 mg once daily to 90 mg once daily, or from 90 mg once daily to 60 mg once daily). Refer to detailed product guideline.
Hepatic Impairment
Severe (Child-Pugh class C): Reduce dose by approx 40% (i.e. from 180 mg once daily to 120 mg once daily, from 120 mg once daily to 90 mg once daily, or from 90 mg once daily to 60 mg once daily). Refer to detailed product guideline.
Administration
film-coated tab: May be taken with or without food. Swallow whole, do not chew/crush.
Contraindications
Lactation.
Special Precautions
Patient taking strong or moderate CYP3A4 inhibitors or CYP3A4 inducers. Severe renal (CrCl 15-29 mL/min) and hepatic (Child-Pugh class C) impairment. Pregnancy.
Adverse Reactions
Significant: Cardiac effects (e.g. hypertension, bradycardia), visual disturbances (e.g. blurred vision, diplopia, photophobia, photopsia, reduced visual acuity, macular oedema, cataract), photosensitivity; elevated creatine phosphokinase (CPK); elevated amylase and lipase, increased ALT, AST or bilirubin; new-onset or worsening hyperglycaemia.
Blood and lymphatic system disorders: Anaemia.
Cardiac disorders: Palpitations, tachycardia, chest discomfort.
Gastrointestinal disorders: Nausea, vomiting, dry mouth, dysgeusia, dyspepsia, constipation, flatulence, diarrhoea, abdominal pain, stomatitis.
General disorders and administration site conditions: Fatigue, oedema, pyrexia.
Investigations: Weight decreased, ECG QT prolonged, increased alkaline phosphatase, increased blood LDH, increased blood creatinine, increased blood cholesterol, increased aPTT; decreased lymphocyte, neutrophil, platelet or WBC count.
Metabolism and nutrition disorders: Decreased appetite, hyperinsulinaemia, hypophosphataemia, hypomagnesaemia, hypercalcaemia, hyponatraemia, hypokalaemia.
Musculoskeletal and connective tissue disorders: Myalgia, arthralgia, pain in extremity, musculoskeletal stiffness, musculoskeletal chest pain.
Nervous system disorders: Headache, dizziness, memory impairment, peripheral neuropathy.
Psychiatric disorders: Insomnia.
Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, URTI, pneumonia.
Skin and subcutaneous tissue disorders: Rash, pruritus, dry skin.
Potentially Fatal: Pulmonary toxicity (e.g. ILD or pneumonitis).
Patient Counseling Information
This drug may cause dizziness, visual disturbances or fatigue; if affected, do not drive or operate machinery. Avoid prolonged sun exposure during treatment and for at least 5 days after stopping the treatment; apply broad-spectrum ultraviolet A (UVA) or ultraviolet B (UVB) sunscreen, lip balm with sun protection factor (SPF) of ≥30 or wear protective clothing when going outdoors. Women of childbearing potential and men with partners who could become pregnant must use proven birth control methods during therapy and for at least 4 months (in women) or at least 3 months (in men) after stopping the treatment.
Monitoring Parameters
Obtain pregnancy test prior to treatment initiation. Confirm ALK-positive status before therapy. Monitor LFTs (e.g. ALT, AST, total bilirubin), CPK, amylase or lipase levels, fasting serum glucose; heart rate, blood pressure. Assess for signs and symptoms of ILD or pneumonitis, muscular symptoms of CPK elevations and visual disturbances.
Drug Interactions
Increased serum concentration with moderate CYP3A4 inhibitors (e.g. diltiazem, verapamil) and strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, voriconazole, indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, telithromycin, troleandomycin, nefazodone). Decreased serum concentration with moderate CYP3A4 inducers (e.g. bosentan, efavirenz, etravirine, modafinil, nafcillin) and strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbital, rifampicin, rifabutin). May reduce serum concentration and efficacy of CYP3A4 substrates with narrow therapeutic index (e.g. alfentanil, fentanyl, quinidine, ciclosporin, sirolimus, tacrolimus). May increase plasma concentration of P-glycoprotein (P-gp) substrates (e.g. colchicine, dabigatran, digoxin, pravastatin), BCRP substrates (e.g. methotrexate, rosuvastatin, sulfasalazine).
Food Interaction
Increased serum concentration with grapefruit or grapefruit juice. Decreased serum concentration with St. John's wort.
Action
Description:
Mechanism of Action: Brigatinib is a multiple tyrosine kinases inhibitor with activity against anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), insulin-like growth factor-1 receptor (IGF-1R), fms-like tyrosine kinase 3 (FLT-3) and epidermal growth factor receptor (EGFR) deletion and point mutations. It blocks ALK autophosphorylation and ALK-mediated phosphorylation of the downstream signalling proteins signal transducer and activator of transcription 3 (STAT3), AKT serine or threonine kinase, extracellular signal-regulated kinase (ERK) 1/2 and ribosomal protein S6 in in vitro and in vivo assays.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 1-4 hours.
Distribution: Plasma protein binding: 91%.
Metabolism: Metabolised in the liver via N-demethylation and cysteine conjugation by CYP2C8 and CYP3A4 isoenzymes.
Excretion: Via faeces (65%; 41% as unchanged drug); urine (25%; 86% as unchanged drug). Elimination half-life: 25 hours.
Chemical Structure

Chemical Structure Image
Brigatinib

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 68165256, Brigatinib. https://pubchem.ncbi.nlm.nih.gov/compound/Brigatinib. Accessed Nov. 22, 2023.

Storage
Store between 15-30°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
MIMS Class
Targeted Cancer Therapy
ATC Classification
L01ED04 - brigatinib ; Belongs to the class of anaplastic lymphoma kinase (ALK) inhibitors. Used in the treatment of cancer.
References
Alunbrig 180 mg Film-coated Tablets (Takeda Pharma A/S). MHRA. https://products.mhra.gov.uk. Accessed 26/07/2023.

Alunbrig 30 mg, 90 mg and 180 mg Film-coated Tablet (Takeda Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 27/07/2023.

Alunbrig 90 mg and 180 mg Film-coated Tablets (Takeda Pharma A/S). MHRA. https://products.mhra.gov.uk. Accessed 26/07/2023.

Alunbrig Tablet, Film Coated (Takeda Pharmaceuticals America, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 26/07/2023.

Anon. Brigatinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 26/07/2023.

Anon. Brigatinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 26/07/2023.

Buckingham R (ed). Brigatinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/07/2023.

Joint Formulary Committee. Brigatinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/07/2023.

Disclaimer: This information is independently developed by MIMS based on Brigatinib 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
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $768 a year.
Already a member? Sign in
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $768 a year.
Already a member? Sign in