Alunbrig

Brigatinib

Monotherapy for the treatment of adult patients w/ anaplastic lymphoma kinase (ALK) +ve advanced NSCLC previously not treated w/ an ALK inhibitor. Monotherapy for the treatment of adult patients w/ ALK +ve advanced NSCLC previously treated w/ crizotinib.

Initially 90 mg once daily for the 1st 7 days, then 180 mg once daily. Patient w/ severe hepatic impairment (Child-Pugh C) Initially 60 mg once daily for the 1st 7 days, then 120 mg once daily. Patient w/ severe renal impairment (eGFR <30 mL/min) Initially 60 mg once daily for the 1st 7 days, then 90 mg once daily.

May be taken with or without food: Swallow whole w/ water, do not crush/dissolve. Avoid grapefruit juice.

Hypersensitivity.

Risk of pulmonary adverse reactions, including ILD/pneumonitis; HTN; bradycardia; visual disturbances; elevations of creatine phosphokinase (CPK), pancreatic enzymes (eg, amylase & lipase), hepatic enzymes (eg, AST, ALT & bilirubin); hyperglycemia; sunlight photosensitivity. Monitor patients for new or worsening resp symptoms, particularly in the 1st wk of treatment. Regularly monitor heart rate, BP, CPK, lipase, & amylase levels during treatment. Assess liver function prior to treatment initiation, then every 2 wk during the 1st 3 mth of treatment; periodically monitor thereafter. Assess fasting serum glucose prior to treatment initiation & monitor periodically thereafter. Avoid concomitant use of strong CYP3A inhibitors; strong & moderate CYP3A inducers. Advise patient to avoid prolonged sun exposure while on treatment, & for at least 5 days after treatment discontinuation. Should not be taken by patients w/ rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Minor influence on the ability to drive & use machines. Women of childbearing potential should use effective non-hormonal contraception during treatment & for at least 4 mth following the final dose. Males w/ female partners of childbearing potential should use effective contraception during treatment & for at least 3 mth after last dose. May cause foetal harm. Should not be used during pregnancy unless clinical condition of the mother requires treatment. Breast-feeding should be stopped during treatment. Safety & efficacy in patients <18 yr have not been established. No available data on patients >85 yr.

Pneumonia, URTI; anaemia, decreased lymphocyte/WBC/neutrophil count, increased aPTT; hyperglycaemia, hyperinsulinaemia, hypophosphataemia, hypomagnesaemia, hypercalcaemia, hyponatraemia, hypokalaemia, decreased appetite; headache, peripheral neuropathy, dizziness; visual disturbances; HTN; cough, dyspnoea; increased lipase, diarrhoea, increased amylase, nausea, vomiting, abdominal pain, constipation, stomatitis; increased AST, ALT, alkaline phosphatase; rash, pruritus; increased blood CPK, myalgia, arthralgia; increased blood creatinine; fatigue, oedema, pyrexia. Decreased platelet count; insomnia; memory impairment, dysgeusia; bradycardia, prolonged ECG QT, tachycardia, palpitations; pneumonitis; dry mouth, dyspepsia, flatulence; increased blood LDH, hyperbilirubinaemia; dry skin, photosensitivity reaction; musculoskeletal chest pain, pain in extremity, musculoskeletal stiffness; non-cardiac chest pain, chest discomfort, pain; increased blood cholesterol, decreased wt.

Increased plasma conc w/ strong CYP3A inhibitors [eg, certain antivirals (indinavir, nelfinavir, ritonavir, saquinavir), macrolide antibiotics (clarithromycin, telithromycin, troleandomycin), antifungals (ketoconazole, voriconazole), nefazodone]; moderate CYP3A inhibitors (eg, diltiazem, verapamil); grapefruit or grapefruit juice. Decreased plasma conc w/ strong CYP3A inducers (eg, rifampicin, carbamazepine, phenytoin, rifabutin, phenobarb, St. John's wort); moderate CYP3A inducers (eg, efavirenz, modafinil, bosentan, etravirine, nafcillin). Reduced plasma levels & efficacy of CYP3A substrates, especially those w/ narrow therapeutic index (eg, alfentanil, fentanyl, quinidine, cyclosporine, sirolimus, tacrolimus). Increased plasma conc of substrates of P-gp (eg, digoxin, dabigatran, colchicine, pravastatin), BCRP (eg, MTX, rosuvastatin, sulfasalazine), organic cation transporter 1 (OCT1), multidrug & toxin extrusion protein 1 (MATE1), & 2K (MATE2K).

Targeted Cancer Therapy

L01ED04 - brigatinib ; Belongs to the class of anaplastic lymphoma kinase (ALK) inhibitors. Used in the treatment of cancer.

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