Paclitaxel-LENS concentrate for solution 6 mg / ml 23.3 ml No. 1 bottle

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Paclitaxel-LENS concentrate for solution 6mg / ml 23.3 ml No. 1 bottle

Composition and release form
Concentrate for solution for infusion 1 ml
paclitaxel 6 mg
excipients: polyoxyl 35 castor oil; anhydrous ethyl alcohol  

in vials of 5, 17, 43.4 ml; in the box 1 bottle.

Description of the dosage form

Transparent colorless or slightly yellowish viscous liquid.

Characteristic

An antitumor drug obtained semi-synthetically from Taxus Baccata.

pharmachologic effect

- antitumor.

Pharmacodynamics

It has an antimitotic effect.
Stimulates the “assembly” of microtubules from dimeric tubulin molecules, stabilizes their structure and inhibits dynamic reorganization in the interphase, which disrupts the mitotic function of the cell.
Causes dose-dependent suppression of bone marrow hematopoiesis. According to experimental data, has mutagenic and embryotoxic properties, causes a decrease in reproductive function.

Pharmacokinetics

When a / in the introduction for 3 h at a dose of 135 mg / m2 Cmax is 2170 ng / ml, the area under the concentration-time curve (AUC) is 7952 ng / h / ml; with the introduction of the same dose over 24 hours - 195 ng / ml, and 6300 ng / h / ml, respectively. Cmax and AUC dose-dependent: with a 3-hour infusion dose increase to 175 mg / m2 leads to an increase in these parameters by 68 and 89%, respectively, with 24-hour administration - by 87 and 26%, respectively. Communication with plasma proteins - 88–98%. Distribution volume - 198–688 l / m2. The half-time from blood to tissue is 30 minutes. It easily penetrates and is absorbed by tissues, accumulates mainly in the liver, spleen, pancreas, stomach, intestines, heart, muscles.

Metabolized in the liver by hydroxylation involving cytochrome P450 isoenzymes CYP2D8 (with the formation of a metabolite — 6-alpha-hydroxypaclitaxel) and CYP3A4 (with the formation of metabolites: 3-para-hydroxypaclitaxel and 6-alpha, 3-para-dihydroxypaclitaxel). Excreted mainly with bile - 90%. With repeated infusions does not accumulate. T1/2 and the total clearance is variable and depends on the dose and duration of intravenous injection: 13.1–52.7 h and 12.2–23.8 l / h / m2 respectively. After intravenous infusion (1–24 h), the total elimination by the kidneys is 1.3–12.6% of the dose (15–275 mg / m2), which indicates the presence of intensive extrarenal clearance.

Indications drug Paclitaxel-LENS

Ovarian cancer - first-line therapy in patients with a common form of the disease or residual tumor (more than 1 cm) after laparotomy (in combination with cisplatin) and second-line therapy for metastases after standard therapy, which did not give a positive result);
breast cancer in the presence of affected lymph nodes after standard combination therapy (adjuvant treatment); after recurrence of the disease, for 6 months after the start of adjuvant therapy - first-line therapy; metastatic breast cancer after an ineffective standard therapy - second-line therapy;
non-small cell lung cancer - first-line therapy in patients who are not planning surgical treatment and / or radiation therapy (in combination with cisplatin);
Kaposi's sarcoma in AIDS patients - second-line therapy, after ineffective therapy with liposomal anthracyclines.

Contraindications

  • hypersensitivity to the drug, as well as other drugs, the dosage form of which includes polyoxyethylated castor oil;
  • pregnancy;
  • breastfeeding period;
  • baseline neutrophil count less than 1500 / μl in patients with solid tumors;
  • the initial or registered in the treatment process, the neutrophil content is less than 1000 / μl in patients with Kaposi's sarcoma in AIDS patients.

Carefully:
  • thrombocytopenia (less than 100,000 / μL);
  • liver failure;
  • acute infectious diseases (including shingles, chicken pox, herpes);
  • severe ischemic heart disease;
  • history of myocardial infarction;
  • arrhythmias.

The safety and efficacy of Paclitaxel-LENS use in children has not been established.

Use during pregnancy and lactation

Contraindicated in pregnancy. At the time of treatment should stop breastfeeding.
Side effects
The frequency and severity of side effects are dose-dependent.
From the side of blood-forming organs: neutropenia, thrombocytopenia, anemia. Suppression of bone marrow function, mainly granulocyte sprout, is the main dose-limiting toxic effect. The maximum decrease in the level of neutrophils is usually observed on days 8–11, normalization occurs on day 22 after administration.
Allergic reactions: in the first hours after the introduction of Paclitaxel-LENS hypersensitivity reactions may occur, which are manifested by bronchospasm, decreased blood pressure, chest pain, flushing of the face, skin rashes, generalized urticaria, angioedema. Described isolated cases of chills and back pain.
On the part of the cardiovascular system: decrease in blood pressure, less often - increase in blood pressure, bradycardia, possible tachycardia, atrioventricular block, ECG changes, vascular thrombosis and thrombophlebitis.
On the part of the respiratory system: interstitial pneumonia, pulmonary fibrosis, pulmonary embolism, as well as more frequent development of radiation pneumonitis in patients simultaneously undergoing radiation therapy.
The nervous system: mainly paresthesia. Rarely, grand mal seizures, visual disturbances, ataxia, encephalopathy, autonomic neuropathy, manifested by paralytic intestinal obstruction and orthostatic hypotension.
From the musculoskeletal system: arthralgia, myalgia.
On the part of the digestive system: nausea, vomiting, diarrhea, mucositis, anorexia, constipation. Single reports of acute intestinal obstruction, intestinal perforation, mesenteric artery thrombosis, ischemic colitis.
On the part of the liver: an increase in the activity of “liver” transaminases (more often AST), alkaline phosphatase and serum bilirubin level. Cases of the development of hepatonecrosis and hepatic encephalopathy are described.
Local reactions: pain, swelling, erythema, induration and skin pigmentation at the injection site; extravasation may cause inflammation and necrosis of the subcutaneous tissue.
On the part of the skin and skin appendages: alopecia, rarely - a violation of pigmentation or discoloration of the nail bed.
Other: asthenia and general malaise.

Interaction

Cisplatin reduces the total clearance of paclitaxel by 20% (more pronounced myelosuppression is observed when paclitaxel is administered after cisplatin).
The simultaneous appointment with cimetidine, ranitidine, dexamethasone or diphenhydramine does not affect the connection of paclitaxel with plasma proteins.
Inhibitors of microsomal oxidation (including ketoconazole, cimetidine, verapamil, diazepam, quinidine, cyclosporine, etc.) inhibit the metabolism of paclitaxel.

Dosage and administration

In / in infusion, in the form of a 3-hour or 24-hour infusion; should be introduced through a system with an integrated membrane filter with a pore size of not more than 0.22 μm.
When preparing, storing and administering Paclitaxel-LENS drug, you should use equipment that does not contain PVC parts.
To prevent severe hypersensitivity reactions, all patients should be premedicated using GCS, H1- antihistamine drugs and H antagonists2- histamine receptors. For example, 20 mg of dexamethasone (or its equivalent) by mouth approximately 12 and 6 hours before the administration of paclitaxel-LENS, 50 mg of diphenhydramine (or its equivalent) in / and 300 mg of cimetidine or 50 mg of ranitidine in / in 30–60 minutes before the introduction of the drug Paclitaxel-LENS.
When choosing a regimen and doses in each individual case, you should be guided by the data of special literature.
Paclitaxel-LENS should be administered intravenously as a 3-hour or 24-hour infusion at a dose of 135-175 mg / m2 with an interval between courses of 3 weeks. The drug is used as monotherapy or in combination with cisplatin (ovarian cancer and non-small cell lung cancer) or doxorubicin (breast cancer).
The recommended dose of Paclitaxel-LENS for the treatment of Kaposi's sarcoma in patients with AIDS is 100 mg / m2 as a 3-hour infusion every 2 weeks. The administration of Paclitaxel-LENS should not be repeated until the neutrophil count is at least 1500 / μl blood and the platelet count is at least 100000 / μl blood. Severe neutropenia (neutrophil count <500 / mm) was observed in patients after the administration of Paclitaxel-LENS3 blood for 7 days or longer) or severe peripheral neuropathy; paclitaxel-LENS should be reduced by 20% in subsequent courses of treatment.
The preparation solution is prepared immediately before administration, diluting the concentrate with 0.9% sodium chloride solution, either with 5% dextrose solution or 5% dextrose solution in 0.9% sodium chloride solution for injection, or with 5% dextrose solution in Ringer's solution to the final concentration 0.3 to 1.2 mg / ml. The prepared solutions can be opalescent due to the presence of the base carrier in the composition of the dosage form, and the solution remains after filtering.

Overdose

Symptoms: aplasia of the bone marrow, peripheral neuropathy, mucositis.
Treatment: paclitaxel's antidote is unknown.

special instructions

The use of Paclitaxel-LENS should be carried out under the supervision of a physician with experience in working with anticancer chemotherapy drugs.
In the case of the development of severe hypersensitivity reactions, the injection of the drug Paclitaxel-LENS should be immediately stopped and symptomatic treatment should be started, and the drug should not be re-administered.
Polyoxyethylated castor oil, which is part of the preparation of Paclitaxel-LENS, can cause extraction of DEGP [di- (2-hexyl) phthalate] from plasticized PVC containers, and the degree of leaching of DEGP increases with increasing solution concentration and with time. Therefore, when preparing, storing and administering Paclitaxel-LENS preparation, you should use equipment that does not contain PVC parts.
During treatment, it is necessary to regularly monitor the picture of peripheral blood, blood pressure, heart rate and the number of breaths (especially during the first hour of infusion), to carry out ECG monitoring (and before the start of treatment).
In cases of development of AV conduction disorders, with repeated administrations, continuous cardiomonitoring should be performed.
If Paclitaxel-LENS is used in combination with cisplatin, Paclitaxel-LENS should be administered first and then cisplatin. Patients during treatment with Paclitaxel-LENS and at least for 3 months after the end of therapy should use reliable methods of contraception.
During the period of treatment, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration of attention and quickness of psychomotor reactions.
Paclitaxel-LENS is a cytotoxic substance, when working with which care must be taken, use gloves and avoid contact with skin or mucous membranes, which in such cases must be thoroughly washed with soap and water or (eyes) with plenty of water.

Storage conditions of the drug Paclitaxel-LENS

In the dark place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

The shelf life of the drug Paclitaxel-LENS

2 years.

Do not use after the expiration date printed on the package.


It is a drug. Consultation with a doctor is required.