Crizotinib INN \n \nIngredients?:?Each capsule contains?250?mg of crizotinib.?Mechanism of action?:Crizotinib?is an inhibitor of receptor tyrosine kinases, including?ALK?, hepatocyte growth?factor receptor?(HGFR?,?c-Met)?,?ROS1 (c-ros)?, and receptord'Origine Nantais ( RON)?.?Metastasis can?affect the?ALK?gene?that leads to the expression of oncogenic fusion proteins?.?The formation of?proteins byALK?fusion?results in the activation and dysregulation of gene expression and signaling, and the proliferation and survival of tumor cells expressing these proteins is increased.?Crizotinib demonstrates?concentration-dependent inhibition?of?ALK?,?ROS1?and?c-Met?phosphorylation in?tumor cell assays,?cell lines in mice expressing echinoderma tumor xenografts and showed anti-tumor activity, microtubule-associated protein Sample?4 (EML4)-?or nuclear protein?(NPM)-ALK?fusion protein or?c-Met?. \n \nPharmacodynamics?:?on the one?52 is?embodiment?ALK?ECG alkylene-positive non-small cell lung cancer patients for study?g azole erlotinib?250?mg, twice daily, maximum average?a QTcF (?corrected by Friedrich's method?QT)?from?The baseline is?12.3?milliseconds?(?two-sided?90%?upper confidence interval?: 19.5?milliseconds?)?.?Quantitative analysis of exposure showed?a concentration-dependent increase in?crizotinib?plasma?QTcF?. \n \nPharmacokinetics?:?Absorption?: After a?single oral dose, crizotinib is absorbed at a median time to a peak?concentration of?4?to?6?hours.?The average absolute bioavailability of crizotinib was?43% (?range?: 32%-66%) after a?single oral dose of?250?mg.?The high-fat meal?reduced?the?AUC ofcrizotinibfrom time zero to infinity?(AUCinf) and the?maximum observed plasma concentration?(Cmax) was?approximately?14%?. \n \nDistribution?:?The geometric mean volume of the distribution of?crizotinib?after intravenous injection was?1772?liters,?giving a?dose of?50?mg, indicating that plasma is widely distributed in tissues. \n \nElimination?: After a?single dose of crizotinib, the mean apparent plasma terminal half-life of crizotinib was?42?hours?for the patient?.?After administration of a single?250?mg radiolabeled crizotinib dose?to healthy?subjects, subjects recovered?63%?and?22%?of the administered dose?in feces and urine, respectively?. \n \nMetabolism?:?Crizotinib is mainly?metabolized?by?CYP3A4/5?.?The main metabolic pathway in which humans epoxidize piperidine to crizotinaractam and dealkylation, followed?by conjugation?of the?second?stage?O?-dealkylated metabolite. \n \nIndications?:?ALK-?positive metastatic non-small cell lung cancer?:?Risone is used to treat patients with metastatic non-small cell lung cancer, and the tumor is an?FDA-?approved test?for anaplastic lymphoma kinase?(ALK)?-positive cell lung cancer?.?ROS1-?positive metastatic non-small cell lung cancer?:?Resorbone is indicated for the treatment of tumor?ROS1?positive in?patients with metastatic non-small cell lung cancer?.?Dosage and Administration?:?The recommended dose of limonic is?250?mg orally twice daily until the disease progresses or is no longer tolerated by the patient.?The recommended dose of lisonone in critically ill patients?does not require dialysis for kidney damage?[?creatinine clearance?< 30?ml?/?min?]?is?250?mg orally once daily.?Rizonib?can be taken with or without food.?Swallow the entire capsule.?If you miss a dose, you should make up, unless the next dose?expires?within?6?hours.?If you take a dose of lisonsone and vomit,?take the next dose. \n \nDose Modification?:?If one or more doses need to be reduced for the following reasons, the dose should be reduced as follows: National Cancer Institute General Term Definition of?Grade?3?or?4?Serious?Adverse Event Adverse Event Standard?(NCI CTCAE)?Version?4.0:?First dose reduction?:?Oral twice daily,?200mg?each time?.?Second dose reduction?:250?mg of?Lissonone once daily?.?If you can't tolerate?250?mg?of Lissonone once a?day?orally?, it will be permanently discontinued.?Or follow the instructions of the registered doctor. \n \nSide effects?:?hepatotoxicity, interstitial lung disease,?prolonged QT interval?, bradycardia, and severe vision loss. \n \nContraindications?:?Components of this product are known to be banned in patients who are allergic to crizotinib or any other drug. \n \nFor pregnancy and breastfeeding?:?no use of crizotinib for pregnant women.?The potential risks of female fetuses with reproductive potential should be communicated to?health care providers who are known or suspected of having a pregnancy.?Women with reproductive potential should be advised to?use effective contraceptive methods?during the treatment with lithonone and at least?45?days?after the final dose?.?Women and men?with reproductive potential?:?Women and men?with reproductive potential should?inform?Rizonib that it?is possible to reduce fertility.?Male patients and female reproductive partners?should advise potential patients to?use condom?doses?during the treatment with lithonone and at least?90?days?after the final treatment?. \n \nBreastfeeding?:?Women should be advised?not to breastfeed the?final dose?during and after?45?days of?treatment with Lisson?.?Rizonib?grams azole imatinib?INN 250?mg capsules?infertility?:?should be advised of the possibility of childbearing potential female and male fertility decline?from Lizuonibu. \n \nDrug interactions?:?Drugs?that?may increase the plasma concentration of crizotinib?:?Crizotinib and strong?cytochrome?P450 (CYP) 3A?inhibitors increase the plasma concentration of crizotinib.?Strong concomitant use?should avoid the use of?CYP3A?inhibitors, including but not limited to atazanavir, clarithromycin, indinavir,?itraconazole, ketoconazole, nefazodone, nelfinavir, Lito Nave, saquinavir, telidromycin, tridomycin, and?voriconazole.?Grapefruit or grapefruit juice should be avoided, which may also increase plasma concentrations?of crizotinib.?Moderate?CYP3A?inhibitors?should be used with caution?.?May?reduce plasma concentrations of crizotinib?:combination?of?crizotinib?and a strong?CYP3A?inducer?reduces plasma concentrations of crizotinib.?The use of strong?CYP3A?inducers?should be avoided?,?including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin and St. John's wort.?Crizotinib may alter plasma concentrations of the drug?:crizotinib?inhibits?CYP3A?in vitro and in vivo.?Simultaneous use of a narrow range of?CYP3A?substrates?should be avoided?,?including but not limited to alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, and?patients taking?crizotinib?Quinidine, sirolimus and tacrolimus.?If accompanied by these?CYP3A?Substrate?Patients taking?crizotinib?require a narrow therapeutic range, and reducing?the dose?ofCYP3A?substrate?may be required for adverse effects. \n \nNote?: \n \nLiver toxicity?:?In?1719?patients, there are?2?Ming?(0.1%)?appeared drug-induced liver toxicity, and lead to death?using Li Songni treatment in clinical trials.?Liver function tests, including alanine aminotransferase, aspartate aminotransferase, and total bilirubin should be?monitored every two weeks during the first two months of treatment, and then monitored monthly, according to clinical instructions,?with more frequent repeated detection of liver transaminases,?Patients with elevated?alkaline phosphatase or total bilirubin?transaminase.?Rizonib?should be suspended, reduced in dose, or permanently discontinued in this case. \n \nInterstitial lung disease?(?pneumonia?):?Severe, life-threatening or fatal interstitial lung disease?(ILD)/?pneumonia can occur in patients treated with lizonone.?Interstitial lung disease usually occurs after the?establishment of?3 Rizonib a?few months later.?Patients with pulmonary symptoms?expressingILD/?pneumonia should be?monitored.?Other potential causes of?ILD/pneumonia should be excluded, and Rizoni should permanently exclude?patients who?are diagnosed with drug-related?ILD/?pneumonia. \n \nQT interval?prolongation?:?QTc?prolongation?may occur in patients receiving treatment with lisonsone?.?The use of?Rizonib?should avoid patients with congenital long?QT?syndrome.?Electrocardiograms and electrolytes should be in?patients with congestive heart failure, bradyarrhythmia, electrolyte abnormalities, or taking medications?known to prolong the?QT interval?.?Rizonib?be in a patient permanently disabled?and?Torsade de?compared to baseline, who appeared greater than?500 ms?or greater than or equal to?60 ms?of the?QTc?changes?sign tip or polymorphic ventricular tachycardia or severe arrhythmia?/?symptoms.?Rizonib?should?restore to a?QTc?before, at least two separate?ECg?appear on more than?500 ms?in?QTc?of?n?patients detained?less than or equal to?480?In milliseconds, in this case, a low dose of Lissonone should be restored. \n \nBradycardia?:?Symptomatic bradycardia can occur in patients receiving lisonsone.?The combination of?Rizonib?with other drugs known to cause bradycardia?(?eg,?beta-?blockers, non-dihydropyridine calcium channel?blockers, clonidine, and digoxin?)?should be avoided as much as possible.?Heart rate and blood pressure should?be monitored regularly.?If there is a life-threatening symptomatic bradycardia, take a dose of lisonsone?before reverting to asymptomatic bradycardia or a heart rate of?60 bpm?or more, reassessing the?combined medication and adjusting the dose of lizonone.?It should stop permanently because?of the life-threatening bradycardia caused by?Rizonib?. \n \nSevere visual loss?:?In all clinical trials,?the incidence of visual impairment with grade?4?visual field loss was?0.2% (4/1719)?.?Optic atrophy and optic nerve disorders have been reported to be potential causes of vision loss.?New severe visual loss?(?best corrected visual acuity is lower than?one or two eyes20/200)?.?Ophthalmic assessment should include best corrected?visual acuity, retinal photographs, visual field, optical coherence tomography, and other assessments?for emerging severe visual loss. \n \nEmbryo?-?fetal toxicity?:?According to its mechanism of action, the injection of lithoni can cause harm to the fetus in?pregnant women.?Pregnant women should be informed of the potential risks to the fetus.?Women of childbearing age?should advise potential patients to use?an effective contraceptive method for?at least?45?days?during the treatment with lithonone?after the last dose.?Male patients with a female partner with reproductive potential should be advised to?use a condom?during treatment with Lithonone and at least?90days?after the final dose?. \n \nOverdose?: There?are currently no known cases of Rizzone overdose.?Rizzoni has no antidote.?Storage?:?Store in a?cool, dry place below?30 ?C?, away from the sun.?Keep out of reach of children. \n \nPacking?:?60?capsules?per carton?, blister pack.