Zykadia

Ceritinib

Anaplastic lymphoma kinase (ALK) +ve locally advanced or metastatic NSCLC.

Recommended & max dose: 450 mg once daily. Severe hepatic impairment Reduce dose to ¹/₃, rounded to nearest multiple of 150 mg.

Should be taken with food: Swallow whole & do not chew/crush.

Permanently discontinue treatment in patients diagnosed w/ any grade treatment-related ILD/pneumonitis; who develop QTc >500 msec or >60 msec change from baseline & Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia; in life-threatening bradycardia if no contributing concomitant medication is identified. Withhold therapy in patients who develop QTc >500 msec on at least 2 separate ECGs until recovery to baseline or QTc <481 msec; in case of symptomatic or life-threatening bradycardia until recovery to asymptomatic bradycardia or heart rate of ≥60 bpm. Avoid use in patients w/ congenital long QT syndrome. Hepatotoxicity; severe life-threatening, or fatal ILD/pneumonitis; QTc prolongation; bradycardia; diarrhea, nausea or vomiting; hyperglycemia; lipase/amylase elevations. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Higher risk of hyperglycemia in patients w/ DM &/or concurrent steroid use. Perform liver lab test including AST, AST & total bilirubin prior to treatment & mthly thereafter. Frequently monitor liver transaminases & total bilirubin in patients who develop transaminase elevations. Periodically monitor ECGs & electrolytes in patients w/ CHF, bradyarrhythmias, or electrolyte abnormalities & those taking medications known to prolong QT interval. Correct electrolytes in case of vomiting, diarrhea, dehydration or impaired renal function. Monitor heart rate & BP regularly; fasting serum glucose, lipase & amylase prior to treatment & periodically thereafter. Monitor & manage GI adverse reactions using anti-diarrheals, anti-emetics, or fluid replacement. Avoid concomitant use w/ drugs known to cause bradycardia eg, β-blockers, non-dihydropyridine Ca channel blockers, clonidine & digoxin. Severe renal impairment. May cause infertility. Women of childbearing potential should use highly effective method of contraception during treatment & up to 3 mth after discontinuation. Pregnancy & lactation. Ped patients <18 yr.

Anemia; decreased appetite; diarrhoea, nausea, vomiting, abdominal pain, constipation, oesophageal disorder; rash; fatigue; liver lab test abnormalities, decreased wt, increased blood creatinine. Hyperglycemia, hypophosphataemia; vision disorder; pericarditis, bradycardia; pneumonitis; abnormal LFTs, hepatotoxicity; renal failure & impairment; prolonged ECG QT, increased lipase & amylase.

Increased AUC_inf & C_max w/ ketoconazole. Avoid concomitant use w/ strong CYP3A inhibitors including ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, & nefazodone; strong CYP3A/P-gp inducers including carbamazepine, phenobarb, phenytoin, rifabutin, rifampin & St. John's wort (Hypericum perforatum); substrates primarily metabolized by CYP3A or CYP3A substrates known to have narrow therapeutic indices eg, ciclosporin, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, tacrolimus, alfentanil & sirolimus; substrates primarily metabolized by CYP2C9 or CYP2C9 substrates known to have narrow therapeutic indices eg, phenytoin & warfarin; grapefruit or grapefruit juice. Increased conc w/ P-gp inhibitors. Decreased AUC_inf, C_max & plasma conc w/ rifampin. Increased AUC_inf of midazolam; warfarin. Increased plasma conc of drugs that are predominantly metabolized by CYP2A6 & CYP2E1. Altered solubility & reduced bioavailability w/ gastric acid reducing agents eg, PPIs, H₂-receptor antagonists, antacids. Increased bioavailability w/ food.

Targeted Cancer Therapy

L01ED02 - ceritinib ; Belongs to the class of anaplastic lymphoma kinase (ALK) inhibitors. Used in the treatment of cancer.

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