Noxalk (Ceritinib) 150 mg 30 tab.

Antitumor tyrosine kinase inhibitor.

Ceritinib inhibits ALA autophosphorylation, ALA-mediated phosphorylation of signaling proteins and proliferation of ALA-dependent tumor cells in vitro and in vivo.

Localization of the ALA gene leads to the spread of the propagated hybrid protein and, as a result, to the systematic activation of the ALA-mediated large helmet was created in the non-small cell lung angle (NSCLC). In most cases, he is the partner for the transaction and is the CEO of EML4. The spreading chimeric protein EML4-ALK contains several ALK components fused to the N-terminal part of EML4. Ceritinib inhibits EML4-ALA kinase in the NSCLC cell line (H2228), which leads to suppression of cell proliferation in vitro and tumor regression in immunodeficient mice and rats carrying xenografts of the H2228 cell line.

Instructions for use NOXALK 150 MG 30 CAPSULES

International or metatestatic non-small cell lung cancer based on anaplastic membrane kinase (ALK).

Instructions for use NOXALK 150 MG 30 CAPSULES

Hypersensitivity to ceritinib; children under 18 years of age (efficacy and safety have not been proven); pregnancy and breastfeeding.

Side effect

From the blood and lymphatic system: very often - anemia; often - anemia (3-4 degrees of severity).

From the side of metabolism: very often - decreased appetite, decreased body weight; often - hyperglycemia, hypophosphatemia, decreased appetite (3-4 degrees of severity), weight loss (3-4 degrees of severity).

On the part of the organ of vision: often - visual impairment (visual impairment, blurred vision, photopsia, floating opacities of the vitreous body, decreased visual acuity, impaired accommodation, presbyopia).

From the side of the average judicial system: frequent pericarditis, bradycardia, seclusion, etc.

From the respiratory system: often - pneumonitis.

From the digestive system: very often - diarrhea, nausea, vomiting, abdominal pain, constipation, esophageal disorders; often - diarrhea (3-4 degrees of severity), abdominal pain (3-4 degrees of severity); infrequently - pancreatitis, constipation (3-4 degrees of severity), esophageal disorders (3-4 degrees of severity), increased lipase activity, increased amylase activity.

From the liver and biliary tract: often - deviations of biochemical parameters of liver function from the norm, hepatotoxicity; infrequently - hepatotoxicity (3-4 degrees of severity).

From the skin and subcutaneous tissues: very often - skin rash; infrequently - skin rash (3-4 degrees of severity).

From the urinary system: very often - increased creatinine concentration; often - renal insufficiency, impaired renal function; infrequently - renal insufficiency (3-4 degrees of severity), impaired renal function (3-4 degrees of severity), infrequently - increased creatinine concentration (3-4 degrees of severity).

General reactions: very often - increased fatigue; often - increased fatigue (3-4 degrees of severity).

Special instructions

Manifestations of hepatotoxicity are usually reversible when therapy is interrupted and/or the dose of ceritinib is reduced; sometimes its cancellation may be required.

Before starting treatment and monthly during therapy, it is recommended to monitor laboratory parameters of liver function (AST including activity, ALT, total bilirubin concentration). According to clinical indications, with an increase in the activity of hepatic transaminases, more frequent monitoring of these indicators should be carried out.

Most cases of severe, life-threatening conditions of pneumonitis were resolved or their course improved with the withdrawal of ceritinib. The patient's condition should be monitored in order to identify symptoms indicating the development of ISL and/or pneumonitis. If ILE and/or pneumonitis of any severity are detected during treatment, other possible causes of ILE and/or pneumonitis should be excluded and the use of ceritinib should be discontinued.

The use of ceritinib should be avoided in patients with congenital QT prolongation syndrome, and caution should be exercised when used in patients with QT prolongation and, including in anamnesis, or predisposition to prolongation of the QT interval, chronic heart failure, bradyarrhythmia, impaired water-electrolyte balance, as well as in patients taking antiarrhythmic and other drugs that prolong the QT interval. It is recommended to periodically monitor the ECG and electrolyte content (for example, potassium) in patients of this category.

According to clinical indications, in case of vomiting, diarrhea, dehydration or impaired renal function, correction of the water-electrolyte balance should be carried out. This is followed by an increase in heart rate with an increase in QTc > 500 ms or more than 60 ms of the total value, as well as with the development of a liquid tachycardia of the "pirouette" type, or polymorphic fluid arrhythmia, or in the presence of symptoms/suggestions for the development of an arrhythmia of the same sequence.

It is necessary to temporarily discontinue the use of ceritinib in patients with a prolongation of the Qt interval > 500 msec until the initial values are restored or until the length of the Qt interval < 481 msec is reduced according to ECG data of at least two, and then resume the use of ceritinib at a dose reduced by 150 mg.

If possible, the simultaneous use of ceritinib and other drugs capable of causing bradycardia (including beta-blockers, non-dihydropyridine calcium channel blockers, clonidine, digoxin) should be avoided. It is necessary to regularly monitor heart rate and blood pressure. If symptoms of bradycardia (which is not life-threatening) occur, it is necessary to temporarily assess the effect of concomitantly used drugs capable of causing bradycardia until they disappear or until the heart rate is restored to 60 beats / min or more, and, if necessary, reduce the dose of ceritinib.

Ceritinib should be discontinued in case of life-threatening bradycardia, if the effect of other drugs on the development of bradycardia has not been established; however, if the effect of other simultaneously used drugs on the development of bradycardia is established, it is necessary to temporarily cancel ceritinib until the symptoms of bradycardia disappear or until a heart rate of 60 beats / min or more is reached, and after dose adjustment of simultaneously used drugs or after their It is recommended to resume treatment with ceritinib at a dose reduced by 150 mg, with more frequent monitoring of the condition.

The patient's condition should be monitored and, if necessary, standard therapeutic measures should be used, including antidiarrheal, antiemetics, as well as infusion therapy. If necessary, ceritinib should be temporarily discontinued or its dose reduced.The risk of hyperglycemia is higher in patients with diabetes mellitus and/or taking GCS. It is necessary to monitor the concentration of glucose in the fasting blood serum before starting therapy with ceritinib, as well as periodically during treatment according to clinical indications. If necessary, hypoglycemic therapy should be initiated or adjusted.

Lipase and amylase activity should be monitored before and during ceritinib therapy in accordance with clinical indications.

Influence on the ability to drive vehicles and mechanisms

Ceritinib has little effect on the ability to drive vehicles and/or machinery. Given the possibility of developing some adverse reactions when using ceritinib (increased fatigue, visual impairment), patients should be careful when driving vehicles and/or mechanisms.