Икземпра®

General characteristics. Structure:

Active ingredient: 15 mg * or 45 mg * иксабепилон.

1 bottle of the enclosed solvent contains 8,0 ml ** or 23,5 ml **: macrogoal глицерилрицинолеат (EL Cremophore) of 4,0 ml or 11,75 ml, ethanol of 4,0 ml or 11,75 ml.

* - Packing is made taking into account a rebookmark in 1 mg for a bottle 15 mg and in 2 mg for a bottle of 45 mg that is necessary for a guarantee of full extraction of the declared dosage. At the same time quantity of an iksabepilon rolled into one taking into account a rebookmark — 16 mg and 47 mg respectively.

** - Packing is made taking into account a rebookmark in 0,8 ml for a bottle 8 ml of willows of 1,5 ml for a bottle of 23,5 ml that is necessary for a guarantee of full extraction of the declared volume. At the same time the content of solvent rolled into one taking into account a rebookmark - 8,8 ml and 25,0 ml respectively.

Pharmacological properties:

Pharmacodynamics. The drug Ikzempra® (иксабепилон) is the representative of a new class of antineoplastic drugs - epotilon and their analogs. Natural epotilona are allocated from Sorangium cellulosum myxobacterium. Epotilona have ability to stabilize dynamics of microtubules that leads to blockade of a mitosis of tumor cells, and, eventually, to their apoptosis and death. The mechanism of binding of natural epotilon and their analogs with tubuliny differs from that at other substances stabilizing microtubules. Iksabepilon — a semi-synthetic analog of an epotilon In, a 16-chlenny poliketidny macrolead in which the lactone is replaced with chemically modified lactam that allowed to increase its stability, extent of linkng with proteins and antineoplastic action.

Iksabepilon has low sensitivity to many factors of tumoral resistance, including to such carriers as a protein of multiple medicinal resistance (MRP-1) and the R-glycoprotein (P-gp), participating in formation of the inborn and acquired resistance to action of antineoplastic means. Communicating with tubuliny, иксабепилон actively inhibits dynamics of microtubules of various R-tubulina isoforms, including pill-isoforms of a tubulin whose excess expression is connected with development of resistance to taxons.

In the conditions of in vivo иксабепилон it is active on various models of a tumor of the person, including the tumor types, steady against action of antineoplastic means, causing an excess expression of P-gp, MRP-1, pill-isoforms of a tubulin or the induced mutations of a tubulin. Iksabepilon shows activity on models of the tumors steady against effect of various drugs, including taxons, anthracyclines and alkaloids of a periwinkle. In combination with kapetsitabiny in the conditions of in vivo a synergism of antineoplastic activity of both drugs is observed. In addition to direct antineoplastic action, иксабепилон has antiangiogenic effect.

Pharmacokinetics. Absorption. At purpose of the drug Ikzempra® in the form of monotherapy in a dosage of 40 mg/sq.m value Stakh (the maximum concentration of an iksabepilon in plasma) was 252 ng/ml (coefficient of variation of CV 56%) and AUC value (the area under a curve "concentration time") - 2143 ¡ú*þ/ml (CV 48%). Usually specified size Stakh was reached upon termination of 3-hour intravenous infusion. At intravenous administration of drug in the range of doses from 15 to 57 mg/m the pharmacokinetics of an iksabepilon is linear.

Distribution. The volume of distribution exceeds 1 Ltd company of l that demonstrates active absorption and binding of an iksabepilon by fabrics. In vitro linkng of an iksabepilon with proteins of serum of the person makes 67-77%; the ratio of concentration in blood/plasma makes 0,65/0,85 in the range of concentration in blood from 50 to 5 Ltd companies of ng/ml.

Metabolism. It is intensively metabolized in a liver, in vitro - by means of CYP3A4 isoenzyme with education more than 30 metabolites, вьшодящихся with urine and a stake.

Removal. The elimination half-life of an iksabepilon at its introduction in a dose of 40 mg/m in the form of 3-hour intravenous infusion makes about 52 hours. It is removed preferential in the form of metabolites. About 86% of the entered dose are removed within 7 days through intestines (65% of a dose) and kidneys (21% of a dose), including in not changed type about 1,6% and 5,6% respectively. At the recommended dosing mode (intravenous infusions are each 3 weeks) accumulation in plasma is not expected.

Pharmacokinetics at special groups of patients. Elderly patients: distinctions of pharmacokinetic parameters at patients of advanced and young age are not revealed.

Children and teenagers: the pharmacokinetics at patients is younger than 18 years was not studied. Patients with abnormal liver functions: the area indicator under a curve concentration time increased by 22% at patients with the serumal concentration of bilirubin exceeding the upper bound of norm no more than by 1,5 times, for 30% at patients with serumal concentration of bilirubin, exceeding the upper bound of norm from 1,5 to 3 times, and for 81% - at the serumal concentration of bilirubin which is three times exceeding the upper bound of norm.

Patients with a renal failure: at patients with a moderate renal failure (clearance of creatinine not less than 28,6 ml/min.) changes of pharmacokinetics of an iksabepilon are not revealed.

Indications to use:

The locally-spread or metastasizing breast cancer at inefficiency of the previous therapy:

- in a combination with kapetsitabiny at inefficiency of the previous therapy by taxons and anthracyclines, at resistance to taxons or in the absence of indications to further therapy by anthracyclines,
- in the form of monotherapy at inefficiency of earlier carried out therapy by taxons, kapetsitabiny and anthracyclines.

Route of administration and doses:

To minimize risk of development of reactions of hypersensitivity, all patients approximately in 1 hour prior to infusion of the drug Ikzempra® should carry out adequate premedication with use:

- H1 blocker - histamine receptors (for example, дифенгидрамин 50 mg inside or its equivalent) and
- H2 blocker - histamine receptors (for example, ranitidine of 150-300 mg inside or 50 mg intravenously, or its equivalent).

In the presence in the anamnesis of hypersensitivity to an iksabepilon in addition to premedication blockers of H1-and N2-of histamine receptors premedication is required by glucocorticosteroids (for example, dexamethasone of 20 mg intravenously in 30 min. prior to drug Ikzempra®ili infusion inside in 12 and 6 hours prior to drug Ikzempra® infusion).

The recommended drug Ikzempra® dose, at its combination with kapetsitabiny, makes 40 mg/sq.m intravenously, in the form of 3-hour infusion each 3 weeks; капецитабин accept 1 Ltd company of mg/sq.m 2 times a day (in 30 min. after food) within 2 weeks, with the subsequent 7-day break. At monotherapy the recommended dose of the drug Ikzempra® makes 40 mg/sq.m intravenously, in the form of 3-hour infusion each 3 weeks. A drug Ikzempra® dose at the surface area of a body exceeding 2,2 sq.m calculate 2,2 sq.m proceeding from body surface area.

Recommendations about correction of a dose of drug. For assessment of possible toxic reactions periodically it is necessary to conduct examination of patients and laboratory researches, including the developed clinical blood test and definition of indicators of function of a liver. At identification of significant toxic reactions treatment should be postponed until their reduction or stopping. Dose adjustment should be carried out at the beginning of each course of treatment on not hematologic signs of toxicity or by quantity of uniform elements of blood (see table 1). A new course of treatment it is necessary to begin at absolute quantity of neutrophils not lower than 1 500 cells / мкл, quantity of thrombocytes it is not lower than 100 000 cells / мкл, at the same time not hematologic signs of toxicity have to decrease. If toxic reactions after an initial dose decline recur, it is recommended to lower a dose by 20%.

Table 1: Dose adjustment of the drug Ikzempra® at toxic reactions.

Not hematologic:	The offered dose adjustment
Neuropathy 3 degrees (heavy) lasting less than 7 days	To lower a dose by 20%
Neuropathy 3 degrees (heavy) duration> 7 days, or disabling neuropathy	To stop therapy
Any toxic reaction 3 degrees (heavy), in addition to neuropathy, or passing an arthralgia / миалгия and fatigue	To lower a dose by 20%
Any toxic reaction 4 degrees (disabling)	To stop therapy

Table 1: Dose adjustment of the drug Ikzempra® at toxic reactions.

Hematologic:
Neutropenia <500 cells / мкл during> 7 days	To lower a dose by 20%
Febrile neutropenia	To lower a dose by 20%
Quantity of thrombocytes <25 Ltd companies / мкл or quantity of thrombocytes <50 Ltd companies / мкл with bleeding	To lower a dose by 20%

 

Renal failures

 Dose adjustment at depression of function of kidneys is not required.
Damages of a liver
At signs of damage of a liver the risk of development of toxic reactions increases. The dose at the first course of treatment should be skorregirovat according to degree of an abnormal liver function (tables 2 and 3). It is necessary to be careful at the activity of serumal ACT or ALT, by 5 times exceeding the upper bound of norm (UBN) as have not enough data concerning therapy such patients.

 
Table 2: The recommended drug Ikzempra®pri doses its combination with kapetsitabiny against the background of an abnormal liver function

	The recommended dose of the drug Ikzempra® (mg/sq.m)
Serumal concentration of bilirubin <1 хВГНи ® Serumal ACT and ALT <2,5 x VGN	40
Serumal concentration bilirubina5> 1 x VGN and • Serumal ACT and ALT> 2,5 x VGN	Contraindicated

 

and Recommendations about doses are intended for the first course of treatment; the further dose decline at the subsequent courses should be carried out depending on individual portability.
b except for patients at whom serumal concentration of the general bilirubin is increased at Gilbert's disease.

 
Table 3: The recommended drug Ikzempra® doses at monotherapy against the background of an abnormal liver function

Activity of transaminases		Serumal concentration bilirubina15	Икземпра® (mg/sq.m) 3
Serumal ACT and ALT <2.5 x VGN	and	<1 x VGN	40
Serumal ACT and ALT> 2.5 x VGN-<10khvgn	and	<1 x VGN	32
Serumal ACT and ALT> 2.5 x VGN-<10khvgn	and	<1.5 x VGN	32
Serumal ACT and ALT <10 HVGN	and	> 1.5 HVGN - <ZhVGN	20-30
Serumal ACT and ALT> 10 HVGN	and/or	> 3 x VGN	Use is not recommended

 

Recommendations about doses are intended for the first course of treatment; the further dose decline at the subsequent courses should be carried out depending on individual portability.
b except for patients at whom serumal concentration of the general bilirubin is increased at Gilbert's disease.

Elderly patients. Clinically significant differences in pharmacokinetics at elderly patients are not revealed. Change of a dose of drug at appointment is not required to elderly patients. At the same time carried out therapy

For the patients who are at the same time receiving powerful inhibitors of an isoenzyme CYP3A4 (for example, кетоконазол, итраконазол, ритонавир, ампренавир, индинавир, нелфинавир, делавирдин, вориконазол), the initial dose of an iksabepilon makes 20 mg/m.

Instructions for preparation and administration of drug. Drug dissolution. Bottles with lyophilisate and solvent take out from the refrigerator and maintain at the room temperature (20 - 25 °C) about 30 min. In the beginning in a bottle with solvent loss of a deposit which is dissolved at achievement of room temperature can be observed.

As well as during the work with other antineoplastic drugs it is necessary to be careful at preparation and administration of solution of an iksabepilon! The specified actions have to be carried out by specially trained personnel with use of protective gloves in the room, specially allotted for these purposes, in aseptic conditions!

In aseptic conditions by means of the syringe of the corresponding size slowly enter solvent into a bottle with lyophilisate.

Bottle contents with a dosage of 15 mg are recovered by means of 8 ml of solvent, bottle contents with a dosage of 45 mg are recovered by means of 23,5 ml of solvent. Carefully shake up a bottle before full dissolution of contents of a bottle. After dissolution concentration of an iksabepilon in solution makes 2 mg/ml. The recovered solution is stable within 1 hour at storage in a bottle (not in the syringe) at the room temperature and room lighting.

Preparation of solution for infusions. Before introduction to the patient the recovered solution has to be divorced with the corresponding infusion solution. For this purpose it is authorized to use the following infusion solutions which have to have рН from 6,0 to 9,0:

• Ringer's solution of a lactate
• Ringer's solution of acetate
• 0,9% chloride sodium solution for injections (When using 0,9% of solution of sodium of chloride for injections it рН should be finished to рН> 6,0, having added Natrii hydrocarbonas solution for injections at the rate of 1 ml (range of concentration from 4,2% to 8,4%) for 250 ml of 0,9% of solution of sodium of chloride, and only then to add solution of an iksabepilon).

At preparation of solution it is necessary to apply the tanks which are not containing DEGF to infusions [di - (2 ethylhexyl) phthalate].

Final concentration of solution for infusions of the drug Ikzempra® has to make from 0,2 mg/ml to 0,6 mg/ml.

For calculation of final concentration of solution for infusions use the following formulas:

• The total amount of infusion = ml of the recovered drug solution + ml of infusion solution
• Final concentration of solution for infusions = a dose of an iksabepilon (mg) / the total amount of infusion (ml)

The necessary amount of the recovered solution with concentration of 2 mg/ml is taken from a bottle by means of the syringe, transferred to a bottle with the corresponding amount of infusion solution and carefully mixed, rotating capacity. For introduction it is necessary to use infusional systems with the filter having diameter of a time from 0,2 to 1,2 microns.

Unused solution for infusions has to be destroyed according to the procedure provided for all antineoplastic drugs. Solution for infusions is stable within 6 hours at storage at the room temperature and lighting. Solution for infusion has to be entered within 3 hours; administration of drug has to be complete not later than in 6 hours after preparation of infusion solution.

Features of use:

Hypersensitivity reactions. All patients before infusion by the drug Ikzempra® should carry out premedication by blockers of Hi-and Ng - histamine receptors and to make observation for identification of reactions of hypersensitivity (for example, asthmas, a bronchospasm, a lowering of arterial pressure). In case of development of the heavy reactions of hypersensitivity, for example, demanding treatment, injection of drug it is necessary to stop and begin immediately the corresponding symptomatic therapy (for example, Epinephrinum, glucocorticosteroids). At development of reactions of hypersensitivity within one cycle at the subsequent cycles it is necessary to carry out premedication, in addition to blockers of Hi-and Ng - histamine receptors, by glucocorticosteroids and to consider the possibility of increase in time of infusion.

Miyelosupressiya. Miyelosupressiya of a dozozavisim is also shown, generally by a neutropenia. For control of development of a miyelosupressiya all patients receiving drug are recommended to carry out clinical blood test regularly. At development of a heavy neutropenia or thrombocytopenia of a dose of drug it is necessary to lower. Peripheral neuropathy

Neuropathy, mainly peripheral touch neuropathy, develops often, and usually happens easy and moderate. At treatment by the drug Ikzempra® it is necessary to make observation of development of symptoms of neuropathy, such as burning sensations, hyperesthesia, hypesthesia, paresteziya, discomfort, neyropatichesky pain. At for the first time the arisen or aggravated peripheral neuropathy can be required to lower a dose, to interrupt a course of treatment, or to cancel drug. At a diabetes mellitus or already available neuropathy the risk of development of heavy neuropathy is increased. At treatment of such patients it is necessary to be careful. The previous therapy by neurotoxic chemotherapeutic drugs risk factor is not.

Damage of a liver. In researches at a breast cancer at activity of serumal ACT or ALT higher than 2,5 x toxicity of the drug Ikzempra® in a dose of 40 mg/sq.m as monotherapy or in combination with kapetsitabiny turned out VGN more expressed, than at activity of serumal ACT or ALT <2,5 x VGN. At monotherapy a neutropenia 4 degrees, a febrile neutropenia, other serious adverse phenomena (thrombocytopenia, a lock, gastrointestinal pains, gastric emptying disturbance, stomatitis, a hyperthermia, a hyperbilirubinemia, a syncope) developed more often. At a combination therapy with kapetsitabiny the general frequency of development of the undesirable phenomena 3-4 degrees (anemia, a leukopenia, thrombocytopenia, the disseminated intravascular coagulating, a neutropenia, an apnoea and cordial activity, abdominal pains, diarrhea, nausea, an esophagitis, vomiting, an adynamy, fatigue, an inflammation of mucous membranes, the infections caused by a neutropenia, pneumonia, respiratory infections, sepsis, septic shock, dehydration, anorexia, a hypovolemia, a metabolic acidosis, a renal failure, dysfunction of respiratory system), a febrile neutropenia, the serious undesirable phenomena (dysfunction of marrow, stenocardia, an atrial flutter, a cardiomyopathy, a myocardial infarction, myocardium ischemia, ventricular dysfunction, colitis, a lock, dyspepsia, gastritis, intestinal impassability, gastrointestinal bleeding, stomatitis, stethalgias, a fever, stethalgias not of a cardiovascular origin, hyperthermia, acute disorder of function of a liver, hypersensitivity, reactions of hypersensitivity of the IV type, bacterial infections, cystitis, an infectious coloenteritis, infections, laryngitis, difficulty of access to vessels at intravenous administration, decrease in quantity of granulocytes, hemoglobin, neutrophils, erythrocytes, leukocytes in blood, a hypopotassemia, a hyponatremia, ostealgias, muscular spasms, a musculoskeletal stethalgia, a mialgiya, a lockjaw, a lack of coordination, a hypesthesia, a lethargy, neuralgia, peripheral neuropathy, paresthesia, peripheral touch neuropathy, a syncope, confusion of consciousness, an acute fluid lungs, a dysphonia, диспноэ, pharyngolaryngeal pains, a mnogoformny erythema, a palmar and bottom eritrodizesteziya, rash, a lowering of arterial pressure, hypovolemic shock, thrombosis, a vasculitis), cases of death connected with toxicity increased.

It is not necessary to appoint the drug Ikzempra® in combination with kapetsitabiny at activity of serumal ACT or ALT higher than 2,5 x VGN or serumal concentration of bilirubin higher than 1 x VGN as at the same time the risk of development of toxic reactions and the mortality connected with a neutropenia increase. It is necessary to appoint with care the drug Ikzempra® as monotherapy at abnormal liver functions and to reduce a dose according to recommendations.

Dysfunctions of heart. Frequency of development of dysfunctions of heart (for example, ischemia of a myocardium and dysfunction of ventricles) at joint reception of an iksabepilon and kapetsitabin was higher (1,9%), in comparison with monotherapy kapetsitabiny (0,3%). It is necessary to be careful at administration of drug of Ikzempra® at patients with heart diseases in the anamnesis. At development of ischemia of a myocardium or dysfunction of heart it is necessary to interrupt a course of treatment with the drug Ikzempra® or to cancel drug.

Possibility of disturbance of cognitive function owing to action of fillers. to an oskolk ethanol is a part of the drug Ikzempra®, it is necessary to consider a possibility of its influence on the central nervous system and other effects.

Elderly patients. Efficiency and safety of the drug Ikzempra® at monotherapy at patients are more senior than 65 years and at more young people are identical.

Necessary efficiency was reached both at young people, and at the elderly patients using the drug Ikzempra® together with kapetsitabiny, however the probability of development of adverse side reactions 3-4 degrees at elderly patients was higher. In this regard at a combination therapy it is necessary to monitor development of side reactions in elderly patients carefully.

Influence on an opportunity to manage motor transport and to work with mechanisms. The special researches studying influence of the drug Ikzempra® on an opportunity to manage motor transport and to work with mechanisms, it was not carried out.

Considering the ethanol content in the solvent attached to the drug Ikzempra® and also possibility of side effects from TsNS which can affect ability to manage motor transport and to work with mechanisms, it is not recommended to drive the car and other mechanisms during treatment by drug.

Side effects:

The most frequent (at more than 20% of patients) the undesirable phenomena at monotherapy by the drug Ikzempra® were: peripheral touch neuropathy, fatigue/adynamy, миалгия / arthralgia, alopecia, nausea, vomiting, stomatitis / мукозит, diarrhea.

At more than 20% of the patients receiving a combination therapy the following reactions in addition developed: palmar and bottom eritrodizesteziya, anorexia, abdominal pains, damages of nails, lock.

By-effects at use of the drug Ikzempra® are presented on the frequency of their registration: very frequent (> 1/10), frequent (> 1/100, <1/10), infrequent (> 1/1 000, <1/100), rare (> 1/10 000, <1/1 000), very rare (<1/1 000).

From laboratory indicators: frequent: decrease in body weight; infrequent: increase in activity of transaminases; rare: increase in activity of an alkaline phosphatase in blood, increase in activity gamma глутамилтрансферазы in serum.

Disturbances from cardiovascular system: frequent: "inflows" with feeling of heat; infrequent: myocardial infarction, dysfunction of ventricles, supraventricular arrhythmia, thrombosis, lowering of arterial pressure; rare: myocardium ischemia, stenocardia, cardiomyopathy, ciliary arrhythmia, hypovolemic shock, thromboembolism of a pulmonary artery, bleeding, vasculitis.

Diseases of blood and lymphatic system: very frequent: neutropenia, thrombocytopenia, anemia, leukopenia; frequent: febrile neutropenia; rare: coagulopathy, lymphopenia.

From a nervous system: very frequent: peripheral touch neuropathy, headaches; frequent: peripheral motive neuropathy, dizziness, taste change, sleeplessness; infrequent: syncope, cognitive disturbances; rare: hemorrhagic stroke, lacks of coordination of movements, drowsiness.

From kidneys and urinary tract: rare: renal failure, nephrolithiasis.

From skin and hypodermic cellulose: very frequent: alopecia; frequent: syndrome of an eritrodizesteziya of fingers of hands and legs, skin rashes, skin hyperpegmentation, itch, skin peeling, damage of nails; rare: multiformny erythema.

From skeletal and muscular system, connecting fabric: very frequent: миалгия / arthralgia, pains of skeletal muscles, infrequent: muscular weakness, rare: muscular spasms, lockjaw.

From respiratory tracts, bodies of a thorax and mediastinum: frequent: short wind, cough; infrequent: respiratory insufficiency, pneumonitis, hypoxia, rare: an acute fluid lungs, a dysphonia, pain in a throat and a throat.

Disbolism and power supply systems: very frequent: anorexia; frequent: dehydration; infrequent: hyponatremia, metabolic acidosis; rare: hypopotassemia, hypovolemia.

From digestive tract: very frequent: stomatitis / мукозит, diarrhea, vomiting, lock, abdominal pains, nausea; frequent: gastroesophageal reflux disease; infrequent: intestinal impassability, colitis, disturbance of evacuation of contents of a stomach, esophagitis; rare: gastrointestinal bleeding, dysphagy, gastritis.

Bacterial and parasitic infections: frequent: upper respiratory tract infections; infrequent: sepsis, infections against the background of a neutropenia, pneumonia, infections of mochevshodyashchy ways, infections; rare: lower respiratory tract infections, coloenteritis, bacterial infection, laryngitis.

The general diseases and diseases developing in a drug injection site: very frequent: fatigue/adynamy; frequent fever, hypostasis, pains in a breast, pains, dacryagogue; rare: fever.

Disturbances from a liver and bilious ways: rare: acute liver failure, jaundice.

From immune system: frequent: hypersensitivity.

Interaction with other medicines:

Kapetsitabin. At the oncological patients receiving иксабепилон in combination with kapetsitabiny of value Stakh and AUC of an iksabepilon decreased by 19% and 6%, a kapetsitabin — for 27% and 5%, a ftoruratsila — increased by 1% and 14%, respectively, in comparison with purpose of an iksabepilon or kapetsitabin separately. This influence is not recognized as clinically significant.

Drugs which can increase concentration of an iksabepilon in a blood plasma. Inductors of an isoenzyme P450 (CYP) of ZA4, can slow down metabolism of an iksabepilon and increase its concentration in plasma. At purpose of the drug Ikzempra® with powerful inhibitors of an isoenzyme CYP3A4 (for example, ketokonazoly, itrakonazoly, ritonaviry, amprenaviry, indinaviry, nelfinaviry, delavirdiny, vorikonazoly) its dose should be reduced. It is also necessary to consider the possibility of purpose of the alternative drugs which are not CYP3A4 isoenzyme inhibitors.

Influence of weak or moderate inhibitors (for example, erythromycin, a flukonazol, verapamil) on system concentration of an iksabepilon was not studied. Therefore it is necessary to be careful at joint reception of these drugs and the drug Ikzempra®, and also whenever possible to appoint the alternative drugs which are not CYP3A4 isoenzyme inhibitors.

At joint therapy by inhibitors of an isoenzyme CYP3A4 and the drug Ikzempra® it is necessary to control more carefully development of acute toxic reactions (for example, regular control of a blood count in intervals between courses of treatment).

Drugs which can reduce concentration of an iksabepilon in plasma. The drugs inducing CYP3A4 isoenzyme (for example, dexamethasone, Phenytoinum, carbamazepine, рифабутин, rifampicin, phenobarbital, drugs of the St. John's Wort which is made a hole) can accelerate metabolism of an iksabepilon and, thereby, reduce its concentration in a blood plasma to subtherapeutic values. Therefore, it is necessary to consider the possibility of appointment along with iksabepilony the drugs which are poorly inducing this isoenzyme.

Influence of the drug Ikzempra® on other drugs. Iksabepilon in the concentration applied in clinical practice does not suppress P450 cytochrome isoenzymes therefore its influence on concentration of other medicines in plasma is not expected.

Contraindications:

- Expressed (3-4 degree according to the standard criteria of toxicity) hypersensitivity in the anamnesis to the EL Cremophore or other drugs containing EL Cremophore or its derivatives (for example, the polyhydroxyethylated castor oil);
- absolute quantity of neutrophils less than 1 500 cells / мкл or thrombocytes less than 100 Ltd companies of cells / мкл;
- in a combination with kapetsitabiny: at activity serumal aspartate aminotransferases (ACT) or alaninaminotranspherase (ALT), by 2,5 times exceeding the upper bound of norm or at the serumal concentration of bilirubin exceeding the upper bound of norm;
- pregnancy and period of feeding by a breast;
- age up to 18 years (efficiency and safety are not established).

With care:

- diabetes mellitus,
- neuropathy,
- liver failure,
- dysfunctions of cardiovascular system in the anamnesis.

Overdose:

Isolated cases of overdose are described by the drug Ikzempra®. Observed at the same time side reactions included peripheral neuropathy, fatigue, musculoskeletal pains / миалгию and gastrointestinal symptoms (nausea, anorexia, diarrhea, abdominal pains, stomatitis).

There is no antidote at overdose by drug. Treatment at overdose has to consist in symptomatic medicinal therapy according to clinical manifestations and in careful observation of the patient.

Storage conditions:

In the place protected from light at a temperature from 2 °C to 8 °C. To store in the place, unavailable to children! A period of validity - 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of solution for infusions complete with solvent. On 15 or 45 mg of lyophilisate in a bottle of colourless glass the type I corked by the brombutilovy stopper rolled by an aluminum cap with a protective plastic cover. On 8,0 or 23,5 ml of solvent for Ikzempra® in a bottle of colourless glass the type I corked by the brombutilovy stopper rolled by an aluminum cap with a protective plastic cover. Place 1 bottle with lyophilisate in a cardboard tray, 1 bottle with solvent. A tray with bottles together with the application instruction in a pack cardboard.