Taxol

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

Indications Taxol

Taxol can be prescribed for malignant tumors of various origins and locations.

• For chemotherapy for ovarian cancer:
  • as initial treatment in combination with cisplatin in patients with disseminated metastases or residual tumor (larger than 10 mm in size) after the first laparotomy;
  • as a second, more complicated treatment option for patients with disseminated metastases to the ovaries, if previous therapy has not produced the expected result.
• For chemotherapy for breast cancer:
  • as an adjuvant postoperative therapy for patients with metastases spreading to the lymph nodes;
  • as initial therapy for further tumor growth after adjuvant treatment with anthracycline drugs;
  • as a more complex treatment option if previous types of therapy have not produced the expected results;
  • as an adjunctive treatment after the use of anthracyclines and cyclophosphamide;
  • as initial treatment for metastatic cancer, in combination with Trastuzumab, if immunohistochemistry indicates HER-2 expression level 3+, with concomitant contraindications to the use of anthracyclines.
• For chemotherapy for non-small cell lung cancer:
  • as initial treatment in combination with Cisplatin, or for unilateral therapy of patients who are not candidates for surgery and radiation.
• For chemotherapy of HIV-associated Kaposi's angiosarcoma:
  • as a more complex treatment after the initial course has not produced positive results.

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Release form

The antitumor drug Taxol is a transparent, viscous liquid, almost colorless, which is a concentrate for the preparation of an infusion solution.

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

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

Names of analogues of the drug Taxol

The antitumor drug Taxol has a fairly large number of analogues with the same active ingredient paclitaxel:

• Abitaxel is a concentrated preparation produced in Argentina;
• Viztaxel is a drug produced by a US-Indian joint venture;
• Intaxel is a drug produced in Germany and India;
• Canataxen is a Canadian concentrated drug;
• Mitotax is a solution produced in India;
• Neotaxel is a concentrated infusion fluid jointly produced by India and Cyprus;
• Paklimedak is a German drug;
• Paklinor is a product of Anglo-Indian production;
• Paclitax is an Indian drug;
• Paclitaxel Ebeve is a medicine from an Austrian pharmaceutical company;
• Paclitaxel Actavis is a drug from a Romanian-Icelandic enterprise;
• Paclitaxel Amaxa is a drug produced in the UK;
• Paclitaxel Maine is a joint product of Australia and the UK;
• 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 Pharmex is a Ukrainian drug;
• Paclitero is a product of Indian manufacture;
• Paklihop is a drug produced by Argentina in collaboration with India;
• Pactalik is a Ukrainian drug;
• Panthium is a medicine produced in India and the UK;
• Praxel is a drug from Mexico;
• Stritoxol is an Indian antitumor drug;
• Taxaval – produced in Luxembourg;
• Taxomeda is a German-Swiss drug;
• Tapaklet is a concentrated medicine produced in India;
• Egilitax is a Hungarian and German medicine.

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Pharmacodynamics

The antitumor drug Taxol is produced by biosynthesis. The principle of the drug's effectiveness is its ability to activate the "binding" of tubular components from dimeric molecular structures of tubulin, inhibit the depolymerization process, and block dynamic rearrangement in the interphase. The listed reactions lead to a disorder of mitotic cellular function.

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

Taxol in certain doses suppresses hematopoietic processes in the bone marrow.

Numerous studies indicate that Taxol may have mutagenic and embryotoxic properties, and may also contribute to a decrease in the reproductive capabilities of the body.

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Pharmacokinetics

The kinetic properties of Taxol were studied after intravenous administration of the drug in amounts of 135 mg/m² and 175 mg/m² for three hours and one day.

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

Kinetic properties lose linearity with increasing dosage. Thus, with a 30% increase in dosage, the maximum concentration increases by 75%.

No cumulative effect of the drug was observed, even with repeated treatment with Taxol.

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

The drug is metabolized in the liver.

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

Approximately one and a half to 12% of the administered amount of Taxol is excreted from the body with urine unchanged, which may indicate intensive extrarenal clearance.

The metabolic characteristics of the drug in patients with impaired renal function have not been determined.

No effect of hemodialysis on the elimination of the drug from the body was detected.

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Dosing and administration

The antitumor drug Taxol is administered intravenously using a drip system.

• In the initial treatment of ovarian carcinoma, the dosage may be 135 mg/m², with subsequent addition of cisplatin. The interval between chemotherapy courses is 21 days.
• Re-therapy for ovarian and breast carcinoma is carried out with 175 mg/m² of the drug, which is administered over 3 hours with an interval of 21 days between chemotherapy courses.
• Initial treatment for non-small cell lung cancer is 175 mg/m² Taxol administered over three hours. The interval between chemotherapy courses is 21 days.

Before treatment with Taxol, patients undergo mandatory premedication, including the use of corticosteroids, antihistamines and H²-receptor antagonists. An approximate premedication scheme may look like this:

• 20 mg Dexamethasone orally 12 hours and 6 hours before the start of Taxol infusion;
• 50 mg Diphenhydramine as an intravenous injection, Cimetidine 300 mg or Ranitidine 50 mg half an hour to an hour before the start of the Taxol infusion.

Immediately before the start of the 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.

Taxol infusion is carried out using a special system with a membrane filter (pore diameter – no more than 0.22 microns).

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Use Taxol during pregnancy

The antitumor drug Taxol is prohibited for use by pregnant and lactating patients.

Women of reproductive age should consider using reliable contraceptive methods before starting treatment with the drug.

Taxol has proven mutagenic and embryotoxic properties.

Contraindications

Taxol should not be prescribed:

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

Conditional contraindications are:

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

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

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Side effects Taxol

Usually, Taxol in standard dosage is well tolerated by patients, regardless of the patient’s age.

Among the most serious side effects, the following can be particularly highlighted:

• suppression of hematopoiesis, severe neutropenia;
• the addition of infection (mainly damage to the respiratory organs);
• decreased platelet levels;
• decreased hemoglobin levels – anemia;
• myelosuppression.

The drug causes allergies relatively rarely, but sometimes such reactions are manifested by a sharp decrease in blood pressure, Quincke's edema, shortness of breath, and widespread rashes.

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

Occasionally, the use of Taxol caused neuropathy, paresthesia, and, very rarely, encephalopathy.

Many patients reported muscle and joint pain.

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

In addition, during treatment it is possible to:

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

Treatment of any side effects is symptomatic. Sometimes the medication is replaced with another one, at the discretion of the doctor.

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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 specific antidote that would neutralize the effects of Taxol, symptomatic treatment is recommended in such cases.

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Interactions with other drugs

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

The use of Doxorubicin in combination with Taxol leads to an excess of doxorubicin and its metabolite in the blood serum. In addition, such a combination of drugs can lead to neutropenia and stomatitis.

Concomitant treatment with Cimetidine, Ranitidine, Dexamethasone and Diphenhydramine does not affect the binding of the active ingredient Taxol to plasma proteins.

In order not to disrupt the metabolic processes of the active ingredient Taxol, it is not recommended to simultaneously administer treatment with drugs that induce or inhibit the CYP2C8 and CYP3A4 isoenzymes (Rifampicin, Phenytoin, Erythromycin, etc.).

In addition, metabolic processes can be suppressed by Ketoconazole, Cyclosporine, Testosterone, Quercetin, Diazepam.

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Storage conditions

Taxol is stored under normal temperature conditions, in a dark place, out of the reach of children.

If the preparation is stored in the refrigerator, a sediment may appear in the solution. When the preparation temperature is brought to room temperature (approximately +20°C), the sediment disappears. This situation does not affect the quality of the preparation in any way.

If the sediment does not dissolve and visible turbidity appears, the medication should be disposed of.

The diluted solution does not lose its properties for 27 hours, however, it is not recommended to store them in the refrigerator, but should be used as soon as possible.

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Shelf life

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