Taxol

A number of antineoplastic and immunomodulating drugs include chemotherapeutic agents - taxanes, of which Taxol is a typical representative. Taxol is a known antitumor medication of plant origin. Its international name is Paclitaxel.

Indications Taxol

Taxol can be prescribed for malignant tumors of various origin and localization.

• For chemotherapy for ovarian cancer:
  • as initial treatment in combination with cisplatin, patients with disseminated metastases or residual tumor process (larger than 10 mm) after the first laparotomy;
  • as a second, complicated, treatment option, patients with disseminated ovarian metastases if the previous therapy did not bring the expected result.
• For chemotherapy for breast cancer:
  • as an auxiliary postoperative therapy, patients with the spread of metastases to the lymph nodes;
  • as an initial therapy for further tumor growth after ancillary treatment with anthracycline drugs;
  • as a complicated treatment option, if previous therapies did not bring the expected results;
  • as an additional treatment after the use of anthracyclines and cyclophosphamide;
  • as an initial treatment for a cancerous tumor with metastases, in combination with the drug Trastuzumab, if immunohistochemical analysis indicated a level of 3+ HER-2 expression, with concurrent contraindications to the use of anthracyclines.
• For chemotherapy for non-small cell lung cancer:
  • as initial treatment in combination with Cisplatinum, or for unilateral therapy of patients who are not shown surgical intervention and irradiation.
• For chemotherapy for HIV-associated angiosarcoma Kaposi:
  • as a more complex treatment after the initial course, which did not bring positive results.

[1], [2], [3], [4], [5],

Release form

Antineoplastic medication Taxol is a transparent viscous liquid that is almost colorless, which is a concentrate for manufacturing an infusion solution.

In 1 ml of the solution contains 6 mg of the active ingredient paclitaxel. Additional ingredients are castor oil and ethanol.

Taxol is bottled in 5 ml bottles, 16.7 ml, 25 ml or 50 ml. Each flakonchik packed in a cardboard box, which is embedded in the annotation to the drug.

The names of analogues of Taxol

Antineoplastic medication Taxol has a sufficiently large number of analogues with the same active ingredient paclitaxel:

• Abitaxel is a concentrated preparation produced by Argentina;
• Viztaksel - a tool produced by a joint US-Indian company;
• Intaksel is a preparation manufactured in Germany and India;
• Kanataksen is a Canadian concentrated drug;
• Mitotax is a solution of Indian production;
• Neotaxel is a concentrated infusion fluid of joint production from India and Cyprus;
• Pacimeduck is a German preparation;
• Paclinor is a tool of Anglo-Indian production;
• Paklitaks is an Indian drug;
• Paclitaxel Ebwee is a medicament of the Austrian pharmaceutical company;
• Paclitaxel Aktavis is a preparation of the Romanian-Icelandic enterprise;
• Paclitaxel Amax is a drug released in the UK;
• Paclitaxel Maine is a joint venture between Australia and the United Kingdom;
• Paclitaxel Vista is an Italian drug;
• Paclitaxel Lens is a Russian concentrate;
• Paclitaxel Teva is a concentrated solution produced in Israel and the Netherlands;
• Paclitaxel Farmex is a Ukrainian drug;
• Paclitero is a product of Indian origin;
• Paklichhop - a preparation produced by Argentina together with India;
• The papalitis is a Ukrainian drug;
• Pantium is a medication manufactured in India and the United Kingdom;
• Praxel - a preparation from Mexico;
• Stritoxol is an Indian antitumour agent;
• Taksaval - manufactured in Luxembourg;
• Taxomede is a German-Swiss drug;
• Tapeclet is a concentrated medicine produced in India;
• Egilitax is a Hungarian and German medicinal product.

[6], [7], [8], [9], [10], [11]

Pharmacodynamics

Antineoplastic medication Taxol is obtained by biosynthesis. The principle of the effectiveness of the drug consists in its ability to activate the "binding" of tubular components from the dimeric molecular structures of tubulin, inhibit the depolymerization process and block the dynamic interchange in the interphase. These reactions lead to a disorder of the mitotic cellular function.

In addition, Taxol provokes the formation of abnormal bonds of tubular components throughout the cell cycle, and also potentiates the formation of a large number of tubular stars during mitosis.

Taxol in certain doses inhibits the blood-forming processes in the bone marrow.

Numerous studies indicate that Taxol may have a mutagenic and embryotoxic property, and also contribute to a decrease in the reproductive capacity of the organism.

[12], [13], [14], [15]

Pharmacokinetics

Kinetic properties of Taxol were studied after intravenous administration of the drug in an amount of 135 mg / m² and 175 mg / m² for three hours and one day.

The content of the active ingredient in the serum is reduced relative to the two kinetic phases. The average Vd is determined in the range from 198 to 688 l / m².

Kinetic properties with increasing dosage lose linearity. Thus, when the dosage is increased by 30%, the limit concentration increases by 75%.

The accumulative effect of the drug has not been observed, even with repeated treatment with Taxol.

The degree of binding to plasma proteins is about 89%.

The metabolism of the drug occurs in the liver.

The half-life and the total clearance may vary, depending on the amount of the drug administered and the duration of the infusion.

Approximately one and a half to 12% of the administered amount of Taxol is excreted from the body with the urinary fluid in an unchanged state, which can speak of intense out-of-cellular clearance.

Metabolic features of the drug with impaired renal function were not determined.

The effect of hemodialysis on excretion of the drug from the body was not detected.

[16], [17], [18], [19], [20], [21], [22]

Dosing and administration

Antineoplastic medication Taxol is administered intravenously, with the help of a drop system.

• In the initial treatment of ovarian carcinoma, the dosage may be 135 mg / m², followed by the addition of cisplatin. The gap between chemotherapy courses is 21 days.
• Repeated therapy of carcinoma of the ovaries and mammary gland is carried out 175 mg / m² of the drug, which is administered 3 hours with an interval between chemotherapy courses at 21 days.
• In the initial treatment of non-small cell lung cancer, 175 mg / m² Taxol is administered, which is administered for three hours. The gap between chemotherapy courses is 21 days.

Before treatment with Taxol, patients undergo mandatory premedication, including the use of corticosteroids, antihistamines, and H 2 receptor antagonists. An exemplary premedication scheme may look like this:

• 20 mg of Dexamethasone by mouth within 12 hours and 6 hours before the start of Taxol infusion;
• 50 mg Diphenhydramine in the form of intravenous injection, cimetidine 300 mg or Ranitidine 50 mg for half an hour before the infusion of Taxol.

 Immediately before the start of infusion, Taxol is diluted to a level of 0.3-1.2 mg per ml with the following solutions:

• isotonic sodium chloride solution;
• 5% glucose;
• 5% glucose in 0.9% sodium chloride;
• 5% glucose in Ringer's injection solution.

Infusion Taxol is carried out using a special system with a membrane filter (pore diameter - not more than 0.22 microns).

[26], [27], [28], [29],

Use Taxol during pregnancy

Antitumor drug Taxol is prohibited for use by pregnant and nursing patients.

Women of reproductive age must first think about the use of reliable contraceptive methods before starting treatment with the drug.

Taxol has proven mutagenic and embryotoxic properties.

Contraindications

Taxol can not be assigned:

• pregnant and lactating women;
• with solid tumors in combination with the level of neutrophils below 1500 per μL;
• with HIV-associated Kaposi angiosarcoma in combination with neutrophil levels below 1000 per μL;
• with the development of severe uncontrolled infectious processes against the background of Kaposi's angiosarcoma;
• with a high probability of developing an allergic reaction to the components of Taxol.

Contingent contraindications are:

• thrombocytopenia (up to 100,000 per μL);
• insufficient liver function;
• acute phase of infectious pathologies;
• complicated course of ischemic heart disease;
• suffered myocardial infarction;
• disturbances of a warm rhythm.

The term "conditional contraindication" means that the use of the drug is allowed, but under the strict supervision of the doctor, with the regular delivery of the necessary tests to monitor the patient's condition.

[23]

Side effects Taxol

Usually Taxol in a standard dosage is tolerated by patients, regardless of the age characteristics of the patient.

Of the most serious adverse events, one can especially distinguish:

• oppression of hematopoiesis, marked neutropenia;
• attachment of infection (mainly the defeat of the respiratory system);
• lowering of platelet count;
• lowering of hemoglobin - anemia;
• myelosuppression.

The drug causes a relatively rare occurrence of the drug, but sometimes such reactions are manifested by a sharp drop in blood pressure, Quinck's swelling, shortness of breath, and widespread eruptions.

In some patients, a slowing of the cardiac activity was observed, accompanied by some changes on the ECG.

Sometimes the use of Taxol caused neuropathy, paresthesia and extremely rarely - encephalopathy.

Many patients had pain in the muscles and joints.

Hair loss was seen in almost all patients undergoing treatment with Taxol.

In addition, during treatment it is possible:

• enlargement of the liver;
• nausea, diarrhea, enterocolitis;
• deterioration of the skin and nails;
• local manifestations at the injection site.

 Treatment of any side symptoms is symptomatic. Sometimes a drug is replaced with another, at the discretion of the doctor.

[24], [25]

Overdose

Possible symptoms of overdose:

• suppression of the hematopoietic function of the bone marrow;
• inflammatory processes in the digestive tract;
• development of peripheral neuropathy.

Since there is no special antidote that would neutralize the action of Taxol, it is recommended that symptomatic treatment be performed in such cases.

[30], [31], [32], [33], [34]

Interactions with other drugs

Cisplatin causes a decrease in the clearance of the active ingredient Taxol en 33%.

The use of Doxorubicin in combination with Taxol leads to an increase in the level of doxorubicin and the product of its metabolism in serum. In addition, this combination of drugs can lead to neutropenia and stomatitis.

Combined treatment with cimetidine, ranitidine, dexamethasone and diphenhydramine does not affect the connection of the active ingredient Taxol with plasma proteins.

In order not to disrupt the metabolism of the active ingredient of Taxol, it is not recommended to simultaneously treat the drugs inducing or inhibiting the isoenzymes CYP2C8 and CYP3A4 (Rifampicin, Phenytoin, Erythromycin, etc.).

In addition, metabolic processes can inhibit ketoconazole, Ciclosporin, Testosterone, Quercetin, Diazepam.

[35], [36], [37], [38], [39]

Storage conditions

Taxol is stored under normal temperature conditions, in a dark place, closed from children's access.

If the drug is stored in the refrigerator, a solution may appear in the solution. When the temperature of the drug is brought to the room temperature (about + 20 ° C), the precipitate disappears. The quality of the drug does not affect this situation in any way.

If the sediment does not dissolve, and the visible turbidity has appeared, then the medicine should be disposed of.

The diluted solution does not lose its properties for 27 hours, but they should not be stored in the refrigerator, but should be used in the near future.

[40], [41], [42]

Shelf life

The antitumor drug Taxol is retained for up to 2 years.