Crizotinib

Oral
Locally advanced non-small cell lung carcinoma, Metastatic non-small cell lung carcinoma

CrCl (mL/min)	Dosage
<30 (not requiring dialysis)	Initially, 250 mg daily, if tolerated, gradually increase to 200 mg bid after at least 4 wk of treatment.

Severe: Contraindicated.

May be taken with or without food.

Congenital long QT syndrome. Severe hepatic impairment. Pregnancy and lactation.

Patient w/ bradyarrhythmias, CHF, electrolyte abnormalities, risk for prolonged QT interval. Mild to moderate hepatic and severe renal (<30 mL/min, not requiring dialysis) impairment.

Significant: Visual loss or impairment, photopsia, blurred vision, diplopia, vitreous floaters, photophobia, bradycardia, nausea and vomiting; severe neutropenia, lymphopenia, and thrombocytopenia.
Nervous: Dizziness, neuropathy, headache, insomnia, fatigue.
GI: Decreased appetite, dyspepsia, diarrhoea, constipation, oesophageal disorders, abdominal pain, stomatitis, dysgeusia.
Resp: Pulmonary embolism, upper resp tract infection, cough.
Hepatic: Increased liver transaminases.
Genitourinary: Increased creatinine, renal cyst.
Endocrine: Hypogonadism.
Musculoskeletal: Arthralgia.
Dermatologic: Rash.
Others: Oedema, fainting, hypophosphataemia, pain, fever.
Potentially Fatal: Hepatotoxicity, QTc prolongation, cardiac failure, GI perforation, interstitial lung disease/severe pneumonitis, hypoxia, acute resp distress syndrome, dyspnoea, empyema, pulmonary haemorrhage, renal failure (including acute cases).

PO: D

This drug may cause vision disorder, symptomatic bradycardia or fatigue, if affected, do not drive or operate machinery.

Monitor CBC, LFT, renal function, heart rate, BP, ECG and electrolytes; ophth evaluation. Assess pulmonary symptoms for interstitial lung disease or pneumonitis.

Plasma concentration is increased by potent CYP3A inhibitors (e.g. atazanavir, clarithromycin, indinavir, ketoconazole, saquinavir) and decreased by CYP3A inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin). Increased risk of bradycardia w/ non-dihydropyridine Ca channel blockers, β-blockers, clonidine, digoxin, anticholinesterases, pilocarpine. Increased risk of torsades de pointes w/ QTc prolonging agents (e.g. disopyramide, quinidine, amiodarone, sotalol, cisapride).

Increased plasma concentration w/ grapefruit or grapefruit juice. Reduced plasma concentration w/ St John’s wort.

Description:
Mechanism of Action: Crizotinib, a tyrosine kinase inhibitor, selectively inhibits anaplastic lymphoma kinase (ALK). In patients w/ ALK-positive non-small cell lung carcinoma (NSCLC), the ALK gene is abnormally activated due to mutations or translocations, which may lead to the expression of oncogenic fusion protein which is responsible for tumour growth. Crizotinib inhibits ALK tyrosine kinase, thus reducing cellular proliferation and survival in tumours which express these fusion proteins. It also inhibits hepatocyte growth factor receptor (HGFR, c-MET), ROS1 (c-ros), and recepteur d’origine nantais (RON).
Pharmacokinetics:
Absorption: Bioavailability: 43%. Time to peak plasma concentration: 4-6 hr.
Distribution: Plasma protein binding: 91%.
Metabolism: Metabolised in the liver via oxidation (to form crizotinib lactam), and O-dealkylation by CYP3A4/5 enzymes.
Excretion: Via faeces (63%, 53% as unchanged drug); urine (22%, 2.3% as unchanged drug). Terminal elimination half-life: 42 hr.

Source: National Center for Biotechnology Information. PubChem Database. Crizotinib, CID=11626560, https://pubchem.ncbi.nlm.nih.gov/compound/Crizotinib (accessed on Jan. 22, 2020)

Store between 20-25°C.
This is a cytotoxic drug. Any unused portion should be disposed of in accordance with local requirements.

Liệu pháp nhắm trúng đích

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

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

Anon. Crizotinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/05/2017.

Buckingham R (ed). Crizotinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com.

Joint Formulary Committee. Crizotinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com.

Xalkori Capsule (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/05/2017.