Taksakad

General characteristics. Structure:

Active ingredient: Paklitakset 6 mg.

Excipients: macrogoal глицерилрицинолеат, ethanol.

Pharmacological properties:

Pharmacodynamics. Таксакад® (paklitakset) is the antineoplastic drug received in the semi-synthetic way.

The mechanism of action is connected with ability to stimulate assembly of microtubules from dimeric molecules of a tubulin, to stabilize their structure due to suppression of a depolymerization and to slow down dynamic reorganization in interphase that breaks mitotic function of a cell. Besides, paklitakset induces formation of abnormal accumulations, or "linking" of microtubules throughout a cellular cycle and causes formation of multiple stars of microtubules during a mitosis.
 
On experimental data, drug has mutagen and embriotoksichesky properties, causes decrease in reproductive function.
 
Pharmacokinetics. Concentration of a paklitaksel in a blood plasma after intravenous administration decreases according to two-phase kinetics.

The pharmacokinetics of a paklitaksel was defined after infusion of drug in doses of 135 and 175 mg/m for 3 and 24 hours. The elimination half-life and the general clearance of a paklitaksel are variable and depend on a dose and duration of introduction: 13,0 - 52,7 h and 12,2 - 23,8 l/h/m, respectively. The average volume of distribution makes from 198 to 688 l/m.

At multiple courses of treatment cumulation of a paklitaksel is noted.

Communication with proteins of plasma makes 89%.

In the researches in vitro on microsomes of a liver it is revealed that paklitakset it is metabolized in a liver with the participation of CYP2C8 isoenzyme to an alpha gidroksipaklitaksel and with the participation of CYP3A4 isoenzyme to 3-para-gidroksipakitakset and 6 - alpha 3-paradigidroksipaklitaksela.

After intravenous infusion of a paklitaksel (15 - 275 mg/m) throughout the 1, 6 or 24 p 1,3 - 12,6% of the entered dose were removed by kidneys in not changed look. After 3-hour infusion of a radioactive paklitaksel in doses of 225 - 250 mg/m during 120 h 14% of radiopharmaceutical 71% - intestines were removed by kidneys. 5% of the entered radiopharmaceutical were removed by intestines in not changed look, other part was made by metabolites, mainly, 6 - alpha гидроксипаклитаксел.

Indications to use:

Ovarian cancer:
 
- Therapy of the 1st line in a combination with platinum drugs at patients with widespread ovarian cancer or with a residual tumor (more than 1 cm) after the carried-out initial laparotomy;
 
- Therapy of the 2nd line at patients with metastatic ovarian cancer later
 the standard therapy which did not yield a positive take.

Breast cancer:

- Adjuvant therapy at patients with existence of metastasises in lymph nodes after performing the standard combined treatment;
 
- Therapy of the 1st line at patients with a late stage of cancer or metastatic cancer after the disease recurrence within 6 months later began performing adjuvant therapy with inclusion of drugs of an anthracycline row, in the absence of contraindications for their use;
 
- Therapy of the 1st line at patients with a late stage of cancer or with a metastatic breast cancer in a combination with drugs of an anthracycline row in the absence of contraindications for their use, or in a combination with trastuzumaby at patients with immunohistochemical HER-2 expression level confirmed 2+ or 3 +;
 
- Therapy of the 2nd line at patients with a late stage of cancer or with a metastatic breast cancer when progressing a disease after the combined chemotherapy. The previous therapy has to include drugs of an anthracycline row in the absence of contraindications for their use.
 
Not small-celled cancer of a lung:
 
- Therapy of the 1st line in a combination with drug of platinum or in the form of monotherapy at patients to whom performing surgical treatment and/or radiation therapy is not planned.
 
Kaposha's sarcoma caused by AIDS:
 
- Therapy of the 2nd line.

Route of administration and doses:

Premedication. For the warning of heavy reactions of hypersensitivity to all patients premedication with use of glucocorticosteroids, blockers of H1 and H2-histamine receptors has to be carried out, for example:
 
- 20 mg of dexamethasone (or its equivalent) inside approximately in 12 and 6 hours prior to administration of drug Taksakad or 20 mg of dexamethasone intravenously approximately in 30 - 60 minutes prior to administration of the drug Taksakad®,
 
- 50 mg of a difengidramin (or its equivalent) intravenously in 30-60 minutes prior to administration of the drug Taksakad®,
 
- 300 mg of Cimetidinum or 50 mg of ranitidine intravenously in 30-60 minutes prior to administration of the drug Taksakad®.
 
Ovarian cancer:
 
- Therapy of the 1st line
 
- 1 time in 3 weeks: 175 mg/sq.m in the form of 3-hour intravenous infusion with the subsequent administration of drug of platinum
 
or
 
- 1 time in 3 weeks: 135 mg/sq.m in the form of 24-hour intravenous infusion with the subsequent administration of drug of platinum.
 
- Therapy of the 2nd line (monotherapy)
 
- 1 time in 3 weeks: 175 mg/sq.m in the form of 3-hour intravenous infusion.
 
Breast cancer:
 
- Adjuvant therapy. It is carried out after the standard combined treatment. Таксакад® it is entered in a dose of 175 mg/m in the form of 3-hour intravenous infusion. In total carrying out 4 courses of therapy with an interval of 3 weeks is recommended.

- Therapy of the 1st line

■ Monoterapiya:

- 175 mg/sq.m in the form of 3-hour intravenous infusion each 3 weeks.

■ Combination therapy:

- with trastuzumaby: next day after introduction of the first dose of a trastuzumab - 175 mg/sq.m of the drug Taksakad® in the form of 3-hour intravenous infusion each 3 weeks; at good tolerance of a trastuzumab - at once after introduction of the subsequent doses of a trastuzumab.

- with doxorubicine (50 mg/m): in 24 hours after administration of doxorubicine - 220 mg/sq.m of the drug Taksakad® in the form of 3-hour intravenous infusion each 3 weeks.

- Therapy of the 2nd line

- 175 mg/m in the form of 3-hour intravenous infusion each 3 weeks

Not small-celled cancer of a lung:

- Combination therapy

- 175 mg/sq.m in the form of 3-hour intravenous infusion, then platinum drug, each 3 weeks

or

- 135 mg/sq.m in the form of 24-hour intravenous infusion, then platinum drug, each 3 weeks.

- Monotherapy

- 175 mg/m - 225 mg/m in the form of 3-hour intravenous infusion each 3 weeks.

Kaposha's sarcoma caused by AIDS:

- Therapy of the 2nd line

- 135 mg/m in the form of 3-hour intravenous infusion each 3 weeks or

- 100 mg/m in the form of 3-hour intravenous infusion each 2 weeks (45 - 50 mg/m a week).

Preparation of solution for infusion. Solution for infusions is prepared just before introduction. Solution of drug is prepared by cultivation of a concentrate to final concentration of a paklitaksel from 0,3 to 1,2 mg/ml. To Vkachestva of the diluting solution can be used: 0,9% chloride sodium solution, or 5% dextrose solution in 0,9% chloride sodium solution, or 5% dextrose solution in Ringer's solution. The prepared solutions can opalestsirovat because of the dosage form of a basis carrier which is present at structure, and after filtering opalescence of solution remains.
 
Taksakad ® it is necessary to enter through system with the membrane filter (the size of a time no more than 0,22 microns).

If not opened bottles are located in the refrigerator, the deposit which is dissolved again at insignificant hashing (or without hashing) on reaching room temperature can be formed. Quality of a product at the same time does not worsen. If solution remains muddy or if existence of an insoluble deposit is noted, the bottle should be destroyed.
 
Weak solutions should not be stored in the refrigerator.
 
Correction of the mode of dosing. To patients with solid tumors repeated courses of treatment the drug Taksakad® are appointed only after achievement of maintenance of neutrophils not less 1500/mkl blood (1000/mkl at patients with sarcoma of Kaposha caused by AIDS), and the maintenance of thrombocytes - 100000/mkl blood (75000/mkl at patients with sarcoma of Kaposha caused by AIDS). To patients at whom after introduction of Taksakada® the heavy neutropenia developed (the maintenance of neutrophils <500/mkl blood within more than 7 days) or a heavy peripheral neuropathy, at the subsequent courses of treatment Taksakad it is necessary to lower a drug dose by 20%. Нейротоксичноть and a neutropenia are dozozavisimy.

Dose adjustment at sarcoma of Kaposha caused by AIDS. Depending on immunosuppression level at patients with far come AIDS form the following measures are recommended:
 
- Decrease in a peroral dose of dexamethasone (as a part of premedication) to 10 mg;
 
- Drug Taksakad® use only at the maintenance of neutrophils not less 1000/mkl blood, thrombocytes - 75000/mkl;
 
- At a heavy neutropenia (less 500/mkl blood within a week and more) or heavy peripheral neuropathy - reduction of a dose of the drug Taksakad® by 25% at the subsequent courses of therapy;

- If necessary - purpose of a granulotsitarny colony stimulating factor (G-KSF).
 
Use at an abnormal liver function. Drug Taksakad® dose adjustment is recommended to patients with a liver failure and the increased risk of toxicity connected with it (in particular miyelosupressiya of the III-IV degree).
 
It is necessary to establish careful control of a condition of the patient.

Table 1. The recommended doses for patients with an abnormal liver function.

 

Degree of a liver failure			Dose * drug Taksakad®
Activity of "hepatic" transaminases		Concentration of bilirubin in blood serum
24-hour infusion
<2 x VGN	and	≤ 26 µmol/l	135 mg/sq.m
2 - <10 x VGN	and	≤ 26 µmol/l	100 mg/sq.m
<10 x VGN	and	28 - 129 µmol/l	50 mg/m
≥ 10 x VGN	or	> 129 µmol/l	It is not recommended
3-hour infusion
<10 x VGN	and	≤ 22 µmol/l	175 mg/sq.m
<10 x VGN	and	22 - 35 µmol/l	135 mg/sq.m
<10 x VGN	and	35 - 86 µmol/l	90 mg/sq.m
≥ 10 x VGN	or	> 86 µmol/l	It is not recommended
* The recommended doses for the first course of therapy; correction of a dose at the subsequent courses has to be based on individual portability of drug. VGN - the upper bound of norm.

Precautionary measures at use. At preparation, storage and administration of the drug Taksakad® it is necessary to use the equipment which does not contain details from PVC, for example: from glass, polypropylene or polyolefin.
 
Таксакад® is cytotoxic substance during the work with which it is necessary to be careful, use gloves and to avoid its hit on skin or mucous membranes which in such cases need to be washed out carefully soap and water, or (eyes) a large amount of water.

Features of use:

Pregnancy and lactation. Use of drug is contraindicated at pregnancy and during breastfeeding.

Treatment by the drug Taksakad® has to be performed under observation of the doctor having experience with antineoplastic chemotherapeutic drugs. Таксакад® it is necessary to apply in the form of weak solution. Before administration of the drug Taksakad® by the patient premedication has to be carried out by glucocorticosteroids, blockers of Hl and H2-histamine receptors. If Taksakad® is used in a combination with Cisplatinum, at first it is necessary to enter Taksakad®, and then Cisplatinum.

Anaphylaxis and serious reactions of hypersensitivity. Less, than at 1% of patients, despite the carried-out premedication, at use of a paklitaksel serious reactions of hypersensitivity were noted. Frequency and weight of such reactions did not depend on a dose and the scheme of administration of drug. At development of heavy reactions suffocation, inflows, a stethalgia, tachycardia, and also abdominal pains, extremity pains, the increased sweating, increase in arterial pressure were most often observed. At development of heavy reactions of hypersensitivity administration of the drug Taksakad® should be stopped immediately and if necessary to appoint a symptomatic treatment. In similar cases it is impossible to appoint repeated courses of treatment drug.
 
Reactions in an injection site. During intravenous administration of a paklitaksel the following usually easy reactions in an injection site were observed: hypostasis, pain in an injection site, an erythema, sensitivity in an injection site, hemorrhages which can lead to development of cellulitis. Such reactions were more often observed at 24-hour infusion, than at 3-hour. In certain cases the beginning of such reactions was observed both during infusion, and in 7-10 days after it.

Miyelosupressiya. Suppression of function of marrow (mainly, a neutropenia) depends on a dose and the scheme of use of drug and is the main toxic reaction limiting a drug dose. At patients with the previous roentgenotherapy in the anamnesis the neutropenia developed less often and in easier degree, and was not aggravated in process of accumulation in an organism.
 
Cases of development of infections were observed very often, sometimes from the death, including sepsis, pneumonia and a pneumonitis. Infections of urinary tract were noted as the most frequent complicated infections. At patients with immunosuppression (patients with HIV infection and patients with sarcoma of Kaposha caused by AIDS), at least, one opportunistic infection was noted.

Use of a maintenance therapy, including a granulotsitarny colony stimulating factor, is recommended for patients at whom the heavy neutropenia was observed.

Decrease in number of thrombocytes below 100000/mkl was noted, at least, time during therapy paklitaksely, sometimes the maintenance of thrombocytes was lower 50000/mkl. Also cases of bleedings, the majority of which were local, are noted, and the frequency of their emergence did not contact a dose of a paklitaksel and the scheme of introduction.

At use of the drug Taksakad® it is necessary to control a blood pattern regularly. It is not necessary to appoint drug sick with the maintenance of neutrophils less 1500/mkl less 1000/mkl at sarcoma of Kaposha caused by AIDS and with the maintenance of thrombocytes less 100000/mkl (75000/mkl at patients with sarcoma of Kaposha caused by AIDS). At development of a heavy neutropenia (<500/mkl) within more than 7 days at the subsequent courses of treatment the dose of the drug Taksakad® should be lowered by 20% (at patients with sarcoma of Kaposha caused by AIDS - for 25%).

Influence on cardiovascular system. The decrease, increase in arterial pressure and bradycardia which are observed during introduction of a paklitaksel usually in a bessimptomna and in most cases do not demand treatment. The lowering of arterial pressure and bradycardia were observed usually within the first 3 hours of infusion.
 
Also disturbance cases on an ECG in the form of disturbances of repolarization such as sinus tachycardia, sinus bradycardia and early extrasystole were noted.
 
In hard cases treatment by the drug Taksakad® should be suspended or stopped. Control of indicators of the vital functions, especially within the first hour of infusion of drug is recommended. If Taksakad® is applied in a combination with trastuzumaby or doxorubicine to treatment of a metastatic breast cancer, control of cordial function is recommended.
 
At treatment paklitaksely cases of heavy disturbances of cordial conductivity are noted. At detection of symptoms of disturbance of cordial conductivity by the patient it is necessary to appoint the corresponding therapy along with a constant ECG - monitoring of cardiovascular system.
 
Influence on a nervous system. Frequency and weight of disturbances from a nervous system generally were dozozavisimy. At treatment paklitaksely the peripheral neuropathy which is usually moderately expressed is often noted. Frequency of development of a peripheral neuropathy increased in process of accumulation of drug in an organism. Cases of paresthesia were often observed in the form of a hyperesthesia. At a heavy neuropathy at the subsequent courses of treatment the dose of the drug Taksakad® should be lowered by 20% (at patients with sarcoma of Kaposha caused by AIDS - for 25%). The peripheral neuropathy can be the cause of the termination of therapy by the drug Taksakad®. Symptoms of a neuropathy decreased or completely disappeared within several months after the therapy termination by drug. Development of a neuropathy is not a contraindication for purpose of the drug Taksakad®)

Cases of disturbance of evoked potential of an optic nerve at patients with permanent injury of an optic nerve were seldom noted.

It is necessary to take possible influence of ethanol which contains in the drug Taksakad® into account.
 
Influence on digestive tract. Cases of nausea/vomiting/diarrhea, a mukozit easy and moderate severity were very often noted at all patients. Cases of development of a mukozit depended on the scheme of administration of drug and were more often observed at 24-hour infusion, than at 3-hour.
 
Exceptional cases of a neytropenichesky coloenteritis (typhlitis), despite joint purpose of a granulotsitarny colony stimulating factor, were observed at the patients applying paklitakset in the form of monotherapy and in a combination with other chemotherapeutic drugs.
 
Liver failure. Patients with a liver failure represent special risk group of development of the miyelosupressiya connected with toxicity of side effects, especially 3-4 degrees. It is necessary to establish careful control of a condition of the patient and if necessary to consider a question of correction of a dose of drug.
 
Contraception. Patients during treatment by the drug Taksakad® and, at least, within 3 months after the end of therapy should use reliable methods of contraception.

Influence on ability to manage vehicles and mechanisms. The drug Taksakad® contains ethanol therefore during treatment it is necessary to refrain from driving and work with potentially dangerous mechanisms. The premedication which is carried out to the patient before administration of the drug Taksakad® can also make negative impact on ability to concentration of attention.

Side effects:

Side effects, as a rule, do not differ on the frequency and weight at cancer therapy of ovaries, a breast cancer, not small-celled cancer of a lung or Kaposha's sarcoma.

However, at patients with sarcoma of the Galosh caused by AIDS more often than are usually noted and heavier infections (including opportunistic), oppression of a hemopoiesis and a febrile neutropenia proceed.

Side effects at monotherapy. Frequency of emergence of side effects is specified according to the following scale: very often (≥ 1/10), it is frequent (≥ 1/100 - <1/10), infrequently (≥ 1/1000 - <1/100), is rare (≥ 1/10000 - <1/1000), is very rare (<1/10000), frequency is unknown (it cannot be estimated by means of available data).

Note: * post-marketing data on side effects of a paklitaksel are noted.

From bodies of a hemopoiesis: very often: miyelosupressiya, neutropenia, anemia, thrombocytopenia, leukopenia, fever, bleedings. Редко*: febrile neutropenia. Very much редко*: acute myeloid leukosis, miyelodisplastichesky syndrome.

From immune system. Very often: the insignificant hypersensitivity reactions which are generally shown in the form of a hyperemia ("inflows") and skin rash. Infrequently: the expressed hypersensitivity reactions demanding treatment, for example, a lowering of arterial pressure, a Quincke's disease, breath dysfunction, a generalized small tortoiseshell, hypostasis, dorsodynias, a fever). Редко*: anaphylactic reactions (including with a lethal outcome). Very much редко*: acute anaphylaxis.

From a nervous system. Very often: neurotoxicity (mainly, peripheral neuropathy). Редко*: the motor neuropathy resulting in insignificant weakness of extremities. Very much редко*: confusion of consciousness, the vegetative neuropathy which is shown paralytic impassability of intestines and orthostatic hypotension, epileptic seizures like "grand mal", spasms, encephalopathy, dizziness, a headache, an ataxy.

From cardiovascular system. Very often: changes on the electrocardiogram (ECG), a lowering of arterial pressure. Often: bradycardia. Infrequently: increase in arterial pressure, fibrinferments, thrombophlebitis, a cardiomyopathy, symptomless ventricular tachycardia, tachycardia with a bigeminal pulse, an atrioventricular block and a syncope, a myocardial infarction. Very much редко*: fibrillation of auricles, supraventricular tachycardia, shock.

From respiratory system. Редко*: asthma, pleural exudate, respiratory insufficiency, intersticial pneumonia, pneumosclerosis, embolism of a pulmonary artery. Very much редко*: cough.

From the alimentary system. Very often: nausea, vomiting, diarrhea, mukozit. Редко*: intestinal impassability, perforation of intestines, ischemic colitis, pancreatitis. Very much редко*: thrombosis of a mesenteric artery, pseudomembranous colitis, esophagitis, lock, ascites, anorexia.

From a liver and biliary tract. Very much редко*: гепатонекроз (with a lethal outcome), hepatic encephalopathy (with a lethal outcome).

From an organ of sight. Very much редко*: reversible damages of an optic nerve and/or vision disorder (ophthalmic migraine, or eye migraine), photopsia, destruction of a vitreous of an eye. Frequency неизвестна*: macular hypostasis.

From an acoustic organ. Very much редко*: hearing loss, sonitus, вертиго (vestibular dizziness), ototoxicity.

From skin, hypodermic cellulose and appendages of skin. Very often: alopecia. Often: temporary minor changes of skin and nails. Редко*: an itch, rash, an erythema, phlebitis, an inflammation of a hypodermic fatty tissue, skin exfoliation, a necrosis and fibrosis of skin, the damages of skin reminding effects of radiation therapy. Very much редко*: Stephens-Johnson's syndrome, epidermal necrolysis, mnogoformny exudative erythema, exfoliative dermatitis, small tortoiseshell, онихолизис. Frequency is unknown: scleroderma, skin red волчанка*.

From a musculoskeletal system. Very often: arthralgia, mialgiya. Frequency неизвестна*: system lupus erythematosus.
 
Local reactions. Often: local hypostasis, pain, erythema, induration.

From laboratory indicators. Often: increase in activity of aspartate aminotransferase (ACT), increase in activity of an alkaline phosphatase. Infrequently: increase in concentration of bilirubin. Редко*: increase in concentration of serumal creatinine.
 
Others. Very often: accession of consecutive infections. Infrequently: septic shock. Редко*: pneumonia, sepsis, adynamy, febricula, fervescence, dehydration, peripheral hypostases. Frequency неизвестна*: syndrome of a lysis of a tumor.
 
Side effects at a combination therapy:
 
- Paklitaksel + Cisplatinum in the 1st line of therapy of ovarian cancer. Frequency and severity of a neurotoxicity, arthralgia / миалгии and hypersensitivity are higher in comparison with therapy by cyclophosphamide and Cisplatinum. On the contrary, manifestations of a miyelosupressiya are noted less often and are expressed more weakly, than at use of cyclophosphamide and Cisplatinum. Manifestations of a heavy neurotoxicity at use in a combination with Cisplatinum in a dose of 75 mg/m are noted less often when using a paklitaksel in a dose of 135 mg/m in the form of 24-hour infusion, than at its introduction in a dose of 175 mg/m in the form of 3-hour infusion.

- Paklitaksel + трастузумаб in therapy of a breast cancer. At use of a paklitaksel in a combination with trastuzumaby in the 1st line of therapy of a metastatic breast cancer following side effects were noted more often than at monotherapy paklitaksely: heart failure, infections, a fever, fever, cough, rash, an arthralgia, tachycardia, diarrhea, increase in arterial pressure, nasal bleeding, an acne, herpetic rashes, accidental injuries, sleeplessness, rhinitis, sinusitis, reactions in an injection site.
 
At use of a paklitaksel in a combination with trastuzumaby in the 2nd line of therapy (after drugs of an anthracycline row) led to increase in frequency and weight of disturbances of cordial activity (in rare instances from the death) in comparison with monotherapy paklitaksely. In most cases side effects were reversible after purpose of the corresponding treatment.

- Paklitaksel + doxorubicine in therapy of a breast cancer. Cases of congestive heart failure at the patients who were earlier not receiving chemotherapy were noted. At the patients receiving chemotherapy courses earlier, especially using anthracyclines disturbance of cordial activity, reduction of fraction of emission of a left ventricle and ventricular insufficiency were often noted. The myocardial infarction was in rare instances noted.
 
- Paklitaksel + radiation therapy. At patients to whom at the same time appointed paklitakset also radiation therapy, cases of a beam pneumonitis were noted.

Interaction with other medicines:

Cisplatinum: At introduction of a paklitaksel after Cisplatinum the miyelosupressiya is expressed stronger, and clearance of a paklitaksel 33% lower, than at introduction of Cisplatinum after a paklitaksel.
 
Doxorubicine: At use of a paklitaksel with doxorubicine the content of doxorubicine and its active metabolite of a doksorubitsinol in blood serum can increase. Such side effects as a neutropenia and stomatitis, are expressed stronger at use of a paklitaksel before administration of doxorubicine, and also when performing longer infusion, than it is recommended.
 
Substrates, inductors and inhibitors of isoenzymes of CYP2C8 and CYP3A4: Paklitaksel is metabolized with the participation of isoenzymes of CYP2C8 and CYP3A4 therefore it is necessary to be careful when using a paklitaksel against the background of treatment by substrates (for example, midazolam, буспирон, фелодипин, ловастатин, элетриптан, sildenafit, симвастатин, to triazoles, репаглинид and розиглитазон), inductors (for example, rifampicin, carbamazepine, Phenytoinum, эфавиренз, not Virapinum) or inhibitors (for example, erythromycin, fluoxetine, gemfibrozit, кетоконазол, ритонавир, индинавир, нелфинавир) these isoenzymes.

Contraindications:

- Hypersensitivity to the paklitaksel or any component which is a part of drug, especially to a macrogoal to a glitserilritsinoleat (the polyhydroxyethylated castor oil);
 
- The initial maintenance of neutrophils less 1500/mkl at patients with solid tumors;
 
- The initial or registered in the course of treatment maintenance of neutrophils less 1000/mkl at patients with sarcoma of Kaposha caused by AIDS;
 
- The accompanying serious uncontrollable infections at patients with Kaposha's sarcoma;

- Pregnancy and period of feeding by a breast;

 
- Children's age (there are no sufficient data on safety and efficiency of drug).
 
With care. Thrombocytopenia (less 100000/mkl), a liver failure, acute infectious diseases (including shingles, chicken pox, herpes), the heavy course of coronary heart disease, a myocardial infarction (in the anamnesis), arrhythmias.

Overdose:

Symptoms: marrow aplasia, peripheral neuropathy, mukozita.

Treatment: symptomatic. The antidote to a paklitaksel is not known.

Storage conditions:

In the place protected from light, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use drug after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 5 ml (30 mg), 16,7 ml (100 mg), 23,3 ml (140 mg), 25 ml (150 mg), 35 ml (210 mg), 41,7 ml (250 mg), 43,3 ml (260 mg), 46 ml (276 mg), 50 ml (300 mg) and 60 ml (360 mg) in the bottles of neutral glass I of a hydrolytic class corked by traffic jams with a teflon covering, with a running in aluminum caps. On each bottle paste the label. On 1 bottle together with the application instruction place in a pack from a cardboard.