Alunbrig

Monotherapy for adults w/ anaplastic lymphoma kinase (ALK)- +ve advanced NSCLC previously not treated w/ ALK inhibitor. Monotherapy for adults w/ ALK-+ve advanced NSCLC previously treated w/ crizotinib.

Initially 90 mg once daily for the 1st 7 days, then 180 mg once daily. If interrupted for ≥14 days, resume at 90 mg once daily for 7 days before increasing to the previously tolerated dose. Dose adjustment: 90 mg once daily (1st 7 days): 1st reduction: Reduce to 60 mg once daily. 180 mg once daily: 1st dose reduction: Reduce to 120 mg once daily. 2nd dose reduction: Reduce to 90 mg once daily. 3rd dose reduction: Reduce to 60 mg once daily. Patients w/ severe hepatic impairment (Child-Pugh class C) Initially 60 mg once daily for the 1st 7 days, then 120 mg once daily. Patients 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, do not crush/chew. Avoid grapefruit or grapefruit juice.

Hypersensitivity.

Patients w/ history of ILD or drug induced-pneumonitis. Monitor for new or worsening resp symptoms (eg, dyspnoea, cough) particularly in the 1st wk of treatment. Withhold treatment if pneumonitis, severe HTN (≥Grade 3), bradycardia, severe creatine phosphokinase (CPK); lipase & amylase abnormalities; AST, ALT & bilirubin elevation, until adequate hyperglycaemic control is achieved occurs. Regularly monitor BP & heart rate (if concomitant use w/ drugs known to cause bradycardia cannot be avoided), CPK levels, lipase & amylase levels, liver function including AST, ALT & total bilirubin during treatment. Discontinue treatment if life-threatening bradycardia occurs. Perform ophthalmologic evaluation for new or worsening severe visual symptoms & consider dose reduction. Assess liver function (AST, ALT & total bilirubin) prior to treatment, & perform monitoring thereafter, then every 2 wk during the 1st 3 mth of treatment; fasting serum glucose prior to treatment & periodically monitor thereafter. Avoid concomitant use w/ strong CYP3A inhibitors, & strong & moderate CYP3A inducers; concomitant use w/ drugs known to cause bradycardia. Women of childbearing potential should use effective non-hormonal contraception during & for at least 4 mth after treatment. Men w/ female partners of childbearing potential should be advised to use effective contraception during & for at least 3 mth after treatment. Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Minor influence on the ability to drive & use machines. Pregnancy & lactation.

Pneumonia, URTI; anaemia, decreased lymphocyte count, increased aPTT, decreased WBCs & neutrophil; hyperglycaemia, hyperinsulinaemia, hypophosphataemia, decreased appetite, hypokalaemia, hypomagnesaemia, hyponatraemia, hypercalcaemia; headache, peripheral neuropathy, dizziness; visual disturbance; HTN; cough, dyspnoea; increased lipase, nausea, diarrhoea, increased amylase, vomiting, constipation, abdominal pain, 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; tachycardia, prolonged ECG QT, bradycardia, palpitations; pneumonitis; dry mouth, dyspepsia, flatulence; increased blood LDH, hyperbilirubinaemia; dry skin, photosensitivity reaction; pain in extremity, musculoskeletal chest pain & stiffness; pain, non-cardiac chest pain, chest discomfort; increased blood cholesterol, decreased wt.

Increased AUC & C_max w/ strong CYP3A inhibitors eg, certain antivirals (indinavir, nelfinavir, ritonavir, saquinavir), macrolides (clarithromycin, telithromycin, troleandomycin), antifungals (eg, ketoconazole, voriconazole), nefazodone. May increase AUC w/ moderate CYP3A inhibitors (eg, diltiazem & verapamil). May increase plasma conc w/ grapefruit or grapefruit juice. Decreased AUC & C_max w/ strong CYP3A inducer eg, rifampicin, carbamazepine, phenytoin, rifabutin, phenobarb & St. John's wort. May decrease AUC w/ moderate CYP3A inducers eg, efavirenz, modafinil, bosentan, etravirine, nafcillin. May reduce effectiveness of CYP3A substrates w/ narrow therapeutic index (eg, alfentanil, fentanyl, quinidine, cyclosporine, sirolimus, tacrolimus). May increase plasma conc of P-gp substrates (eg, digoxin, dabigatran, colchicine, pravastatin), BCRP substrates (eg, MTX, rosuvastatin, sulfasalazine), organic cation transporter 1 substrates, multidrug & toxin extrusion protein 1 & 2k substrates.

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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