Paclitaxel Actavis

Paclitaxel actavis refers to the pharmacological group of antitumor agents (cytostatics) that are of plant origin. Synonyms: Taxol, Paclitaxel, Paclitaxel Ebwee, Paklitax, Paksen, Paclinor, Paclitaxel-Teva, Paktalik, Paklitera, Docetaxel, Abitaxel, Intaksel, Mitotax, Sindaxel, Taxakad, Yutaksan.

Indications Paclitaxel Actavis

Indications for use Paclitaxel Actavis include such oncological diseases as:

• ovarian cancer;
• breast cancer;
• non-small cell lung cancer (adenocarcinoma, squamous and undifferentiated bronchoalveolar, large-celled, mixed cell carcinoma);
• transitional cell carcinoma of the bladder;
• esophageal cancer;
• lymphocytic and non- lymphocytic leukemia;
• multiple hemorrhagic skin ( Kaposi's sarcoma ).

For patients with diffuse ovarian cancer or residual neoplasia who underwent laparotomy, Paclitaxel actavis is a first-line therapy drug; with metastases after ineffective standard treatment - with the drug of second-line therapy.

In malignant breast cancer, paclitaxel actavis is used in postoperative (adjuvant) treatment - in the presence of affected lymph nodes, in case of recurrence of the disease or the appearance of metastases.

In the treatment of non-small cell lung cancer, this drug is prescribed when surgical intervention or radiation therapy is not expected. The use of paclitaxel actuavis in Kaposi's sarcoma is indicated for patients with AIDS.

[1]

Release form

The form of the preparation is a concentrated liquid formulation for the preparation of a solution for infusions.

[2], [3]

Pharmacodynamics

Active basis of the preparation Paclitaxel actavis and its synonyms are taxanes - nitrogen-containing organic compounds (alkaloids) of the bark of the coniferous tree of the genus Taxus of the class of short-leaved (or Pacific).

The mechanism of cytostatic action is based on the ability of the substance paclitaxel, obtained from taxanes, to inhibit the process of cellular mitosis in the initial phases.

Indirect division (mitosis) of eukaryotic cells begins with the formation in the cytoskeleton of the mitotic apparatus - the achromatin spindle, the mobile filaments of which (microtubules) connect the poles of the cell and its center. After doubling the DNA, the daughter chromosomes in the metaphase stage are concentrated in the center of the cell, and the task of the achromatin spindle microtubules is to move these chromosomes to different poles of the cell, where two new cells appear in the telophase stage.

Microtubules are formed by polymerization of the cytoplasmic globular protein tubulin, and paclitaxel, due to the similarity of taxane with tubulin, binds to molecules of free tubulin. This increases the intensity and degree of polymerization of tubulin and activates the formation of microtubules, resulting in the formation of an excess of microtubules. And due to the suppression of the depolymerization of tubulin microtubules lose the ability to perform their functions. All this leads to a violation not only of the formation of the mitotic apparatus of cells, but also of the stopping of their division.

In addition, under the influence of Paclitaxel actavis (and all drugs with paclitaxel), the normal arrangement of microtubules in the cytoskeleton is disrupted and a number of their anomalous bundles and condensations appear.

[4], [5]

Pharmacokinetics

After entering the bloodstream from 89% to 98%, Paclitaxel actavis binds to proteins. Within 30 minutes, half of the drug penetrates into the tissues of the intestine, liver, spleen, pancreas, heart and muscles.

The concentration of paclitaxel in the blood plasma after intravenous administration is reduced in stages. Biological transformation Paclitaxel actavis occurs in the liver under the influence of cytochrome P450 enzymes - during the hydroxylation reaction, with the formation of a metabolite of 6a-hydroxy-paclitaxel.

The half-life of the drug varies in a wide range - from 3 hours to two days. From the body Paclitaxel actavis is excreted mainly with bile; part of the drug in an unchanged form is eliminated by the kidneys with urine.

[6], [7], [8],

Dosing and administration

All cyclosatic preparations of the taxane group are administered in a hospital, under the supervision and supervision of an oncologist.

In order to prevent the manifestation of a hypersensitivity reaction to the drug Paclitaxel actavis before its use, medicamentous preparation of patients with corticosteroids should be carried out.

Method of application Paclitaxel actavis - intravenous drip (within 3-24 hours). The individual dose is determined in accordance with the treatment protocol. The standard dosage is 135-175 mg / m ². Repeated administration of the drug is performed after 21 days.

Concentrate Paclitaxel actavis before administration is diluted (up to 0,3-1,2 mg / ml), for which one of the solutions for injection - sodium chloride or glucose is used.

It should be borne in mind that the solution ready for administration can not be stored in the refrigerator, and its stability in the light and at a temperature of + 25 ° C remains a maximum of 27 hours.

[13]

Use Paclitaxel Actavis during pregnancy

The use of paclitaxel actavis during pregnancy and during lactation is contraindicated. It has been established that paclitaxel not only exerts embryotoxic action, but also reduces the reproductive capacity of women of childbearing age.

Contraindications

The cytotoxic drug Paclitaxel Actavis is contraindicated in patients with increased individual sensitivity to paclitaxel, acute infectious diseases, coronary heart disease, with a history of myocardial infarction, and also with a low content of neutrophilic granulocytes (neutropenia) in the blood.

[9]

Side effects Paclitaxel Actavis

The use of paclitaxel actavis may accompany side effects in the form of: hair loss; nausea, vomiting and diarrhea; urticaria and skin itching; shortness of breath; edema; disorders of the heart rhythm (tachycardia or bradycardia); increase or decrease in blood pressure; pain in the joints and muscles; renal failure; anemia, neutropenia, or thrombocytopenia.

In the presence of inflammatory pathologies, their exacerbation may occur. Side effects from the central and peripheral nervous system are also manifested, namely: paresthesia, impaired coordination of movements and vision, encephalopathic symptoms (weakness, headache, dizziness, fatigue, sleep disturbance, memory from consciousness).

[10], [11], [12]

Overdose

In case of an overdose of Paclitaxel Actavis, dyspnea, falling AD, angioedema, extensive urticaria, reddening and erosive-ulcerative lesions of the mucous membranes of the mouth and pharynx, and hypoplastic anemia (due to suppression of the hematopoietic function of the bone marrow) are most often observed.

To date, there is no specific antidote for paclitaxel, therefore symptomatic treatment is indicated. With significant overdose, the administration of Paclitaxel Actavis should be stopped.

[14], [15],

Interactions with other drugs

A number of drugs - ethinyl estradiol, retinoic acid, quercetin, ketoconazole, verapamil, diazepam, quinidine, dexamethasone, cyclosporine, vincristine - inhibit the metabolism of Paclitaxel actavis.

The use of paclitaxel actavis in combination with the antitumor antibiotic doxorubicin gives side effects in the form of stomatitis and pronounced neutropenia.

[16], [17]

Storage conditions

The drug refers to List B and it is stored in a dark place at room temperature or in a refrigerator (at a temperature of at least -2 ° C). Storage of unopened vials in the refrigerator can cause a precipitate to appear, which must dissolve at room temperature. Otherwise, the drug becomes unsuitable for use.

[18]

Shelf life

Shelf life of the drug is 24 months.

[19], [20], [21], [22]