Xalkori

Crizotinib

For adults previously treated & untreated w/ anaplastic lymphoma kinase (ALK) +ve advanced non-small cell lung cancer (NSCLC). Treatment of ROS-1 +ve advanced NSCLC.

250 mg twice daily. If dose reduction is necessary, reduce to 200 mg twice daily & may further be reduced to 250 mg once daily.

May be taken with or without food.

Hypersensitivity. Severe hepatic impairment.

Permanently discontinue if treatment-related ILD/pneumonitis is diagnosed. Consider periodic monitoring w/ ECG & electrolytes in patients w/ history of or predisposition for QTc prolongation, or taking QT interval-prolonging drugs; ophthalmological evaluation if vision disorder persists or worsens in severity. Monitor LFTs including ALT, AST & total bilirubin every 2 wk during the 1st 2 mth of treatment, then once mthly & as clinically indicated, w/ more frequent repeat testing for grades 2, 3 or 4 elevations. Caution should be exercised by patients who experience vision disorder, dizziness or fatigue during treatment when driving or operating machinery. Mild & moderate hepatic impairment. Severe renal impairment & ESRD. Male & female fertility may be compromised. Pregnancy & lactation. Women of child-bearing potential should use adequate contraception during & for at least 90 days after therapy. Ped patients.

Neutropenia, leukopenia; decreased appetite; neuropathy, dizziness, dysgeusia; vision disorder; bradycardia; vomiting, diarrhoea, nausea, constipation; elevated transaminases; rash; oedema, fatigue. Prolonged ECG QT, syncope; interstitial lung disease; oesophagitis, dyspepsia; increased blood alkaline phosphatase; renal cyst, increased blood creatinine; decreased blood testosterone.

Increased plasma conc w/ strong CYP3A inhibitors (eg, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir), azole antifungals (eg, itraconazole, ketoconazole, voriconazole), macrolides (eg, clarithromycin, telithromycin, troleandomycin), grapefruit or grapefruit juice. Increased systemic exposure w/ ketoconazole. May alter plasma conc of CYP3A substrates w/ narrow therapeutic indices eg, alfentanil, cisapride, cyclosporine, ergot derivatives, fentanyl, pimozide, quinidine, sirolimus, tacrolimus. Decreased AUC_inf & C_max w/ rifampicin. Decreased plasma conc w/ strong CYP3A inducers eg, carbamazepine, phenobarb, phenytoin, rifabutin, rifampin, St. John's wort. Concomitant use w/ drugs predominantly metabolized by pregnane X receptor-regulated enzymes eg, CYP2B6, CYP2C8, CYP2C9, UGT1A1 (except CYP3A4); substrates of UGTs eg, paracetamol, morphine, irinotecan. Effectiveness of OCs may be altered. May increase therapeutic effect & AR of P-gp substrates eg, digoxin, dabigatran, colchicine, pravastatin. Decreased solubility & subsequently reduced bioavailability w/ drugs that elevate gastric pH eg, PPIs, H₂ blockers, antacids.

Cytotoxic Chemotherapy

L01ED01 - crizotinib ; Belongs to the class of anaplastic lymphoma kinase (ALK) inhibitors. Used in the treatment of cancer.

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