Composition, form of production and packaging
Concentrate for the preparation of a solution for infusions in the form of a transparent, colorless or slightly yellowish, viscous liquid.
1 ml of 1 fl.
paclitaxel 6 mg 30 mg
Excipients: polyoxyl 35 castor oil (macrogol glyceryl hydroxy stearate), ethanol anhydrous.
5 ml - bottles (1) - packs of cardboard.
5 ml - vials (1) complete with an infusion system - packs cardboard.
Concentrate for the preparation of a solution for infusions in the form of a transparent, colorless or slightly yellowish, viscous liquid.
1 ml of 1 fl.
paclitaxel 6 mg 100 mg
Excipients: polyoxyl 35 castor oil (macrogol glyceryl hydroxy stearate), ethanol anhydrous.
17 ml - bottles (1) - packs of cardboard.
17 ml - vials (1) complete with an infusion system - packs cardboard.
Concentrate for the preparation of a solution for infusions in the form of a transparent, colorless or slightly yellowish, viscous liquid.
1 ml of 1 fl.
paclitaxel 6 mg 260 mg
Excipients: polyoxyl 35 castor oil (macrogol glyceryl hydroxy stearate), ethanol anhydrous.
43.4 ml - vials (1) - packs of cardboard.
43.4 ml - vials (1) complete with infusion system - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
The product description was approved by the manufacturer for the 2009 print edition.
PHARMACHOLOGIC EFFECT
Paclitaxel-LENS is an antitumor preparation of natural origin, obtained semi-synthetically from the plant Taxus Baccata.
The mechanism of action is associated with the ability to stimulate the "assembly" of microtubules from dimeric tubulin molecules, stabilize their structure and inhibit dynamic reorganization in the interphase, which disrupts the mitotic function of the cell. Causes a dose-dependent suppression of bone marrow hematopoiesis.
According to experimental data it has mutagenic and embryotoxic properties, it causes a decrease in reproductive function.
PHARMACOKINETICS
Suction
With iv administration of paclitaxel for 3 hours at a dose of 135 mg / m C max is 2170 ng / ml, AUC is 7952 ng / h / ml. With iv administration of paclitaxel for 24 hours at a dose of 135 mg / m, C max is 195 ng / ml and AUC is 6300 ng / h / ml, respectively. C max and AUC are dose-dependent: with a 3-hour infusion, increasing the dose to 175 mg / m 2 leads to an increase in these parameters by 68% and 89%, respectively, at 24-hour - by 87% and 26%, respectively.
Distribution
Binding to plasma proteins - 88-98%. Average V d -198-688 l / m 2 . The time of half-distribution from the blood in the tissue is 30 minutes. Easily penetrates and adsorbed by tissues, accumulates mainly in the liver, spleen, pancreas, stomach, intestines, heart, muscles. With repeated infusions do not cumulate.
Metabolism
It is metabolized in the liver by hydroxylation with the participation of CYP2D8 isoenzymes (with the formation of the metabolite 6 -? - hydroxypaclitaxel) and CYP3CA4 (with the formation of metabolites of 3-para-hydroxypaclitaxel and 6-, 3-para-dihydroxy paclitaxel).
Excretion
It is excreted mainly with bile - 90%. T 1/2 and total clearance are variable and depend on the dose and duration of IV administration: 13.1-52.7 h and 12.2-23.8 l / h / m 2 , respectively. After intravenous infusion (1-24 hours), the total excretion by the kidneys is 1.3-12.6% of the dose (15-275 mg / m 2 ), which indicates the presence of intensive extrarenal clearance. The total ground clearance is 11-24 l / sq.m.
INDICATIONS
- combined with cisplatin therapy of the first line of patients with a common form or residual tumor (> 1 cm) of ovarian cancer after laparotomy;
- second-line therapy for metastases of ovarian cancer 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);
- First-line therapy after a relapse of breast cancer, within 6 months after the initiation of adjuvant therapy;
- second-line therapy for metastatic breast cancer after ineffective standard therapy;
- combined with cisplatin therapy of the first line of patients with non-small-cell lung cancer who are not scheduled for surgical treatment and / or radiation therapy;
- second-line therapy for Kaposi's sarcoma in patients with AIDS after ineffective therapy with liposomal anthracyclines.
DOSING MODE
Paclitaxel-LENS is administered iv in the form of a 3-hour or 24-hour infusion at a dose of 135-175 mg / m 2 with an interval between courses of 3 weeks.
The recommended dose of Paclitaxel-LENS for the treatment of Kaposi's sarcoma in patients with AIDS is 100 mg / m 2 as a 3-hour infusion every 2 weeks.
The drug is used in the form of monotherapy or in combination: in ovarian cancer and non-small cell lung cancer with cisplatin, in breast cancer with doxorubicin.
When choosing the regimen and doses in each individual case, one should be guided by the literature data.
To prevent severe hypersensitivity reactions, all patients should undergo premedication with GCS, antihistamines and histamine H2-blockers. For example, 20 mg of dexamethasone (or its equivalent) orally within about 12 and 6 hours before the administration of the Paclitaxel-LENS preparation, 50 mg of diphenhydramine (or its equivalent), and 300 mg of cimetidine or 50 mg of ranitidine IV in 30-60 min prior to the administration of the Paclitaxel-LENS preparation.
The administration of Paclitaxel-LENS should not be repeated until the neutrophil count is at least 1500 / Ојl of blood and the platelet count is at least 100,000 / ОјL of blood.
Patients who had severe neutropenia (neutrophil count <500 / mm 3 for 7 days or longer) or severe form of peripheral neuropathy after subsequent administration of Paklitaxel-LENS should be reduced by 20% after the administration of Paclitaxel-LENS.
The drug solution is prepared immediately before administration, diluting the concentrate with 0.9% sodium chloride solution, or 5% dextrose solution, or 5% dextrose solution in a 0.9% solution of sodium chloride for injection, or 5% dextrose solution in Ringer's solution to a final concentration of 0.3 to 1.2 mg / ml. The prepared solutions may be opalescent due to the carrier base present in the formulation, after which the opalescence of the solution is retained.
When preparing, storing and administering Paclitaxel-LENS, you should use equipment that does not contain PVC parts.
Paclitaxel-LENS should be administered through a system with an integrated membrane filter (pore size not more than 0.22 microns).
SIDE EFFECT
The frequency and severity of side effects are dose-dependent.
On the part of the hematopoiesis system: neutropenia, thrombocytopenia, anemia. Suppression of bone marrow function, mainly of granulocyte germ, was the main toxic effect limiting the dose of the drug. The maximum decrease in the level of neutrophils is usually observed on day 8-11, normalization occurs on day 22.
From the cardiovascular system: a decrease or increase (less often) AD, bradycardia, tachycardia, AV-blockade, changes in the ECG, vascular thrombosis, thrombophlebitis.
On the part of the respiratory system: interstitial pneumonia, pulmonary fibrosis, pulmonary embolism, radiation pneumonitis in patients undergoing radiotherapy.
From the central nervous system and the peripheral nervous system: paresthesia; rarely convulsive seizures such as grand mal, visual impairment, ataxia, encephalopathy, autonomic neuropathy, manifested by paralytic intestinal obstruction and orthostatic arterial hypotension.
On the part of the digestive system: nausea, vomiting, diarrhea, mucositis, anorexia, constipation, increased activity of hepatic transaminases (often ACT), alkaline phosphatase, bilirubin in serum; single cases - acute intestinal obstruction, perforation of the intestine, thrombosis of the mesenteric artery, ischemic colitis. The cases of development of hepatonecrosis and hepatic encephalopathy are described.
From the musculoskeletal system: arthralgia, myalgia.
Local reactions: pain, swelling, erythema, induration and skin pigmentation at the injection site; Extravasation can cause inflammation and necrosis of subcutaneous tissue.
Dermatological reactions: alopecia; rarely - a violation of pigmentation or discoloration of the nail bed.
Allergic reactions: in the first hours - reactions of increased sensitivity, manifested bronchospasm, lowering blood pressure, pain behind the sternum, flushing of the face, skin rashes, generalized urticaria, angioedema; single cases - chills, back pain.
Other: asthenia, general malaise.
CONTRAINDICATIONS
- initial neutrophil count <1500 / ОјL in patients with solid tumors;
- the initial or registered in the course of treatment of neutrophil count <1000 / ОјL in Kaposi's sarcoma in patients with AIDS;
- Pregnancy;
- the period of breastfeeding;
- hypersensitivity to drugs, the dosage form of which includes polyoxyethylated castor oil.
Caution should be used when thrombocytopenia (<100 000 / Ојl), liver failure, acute infectious diseases (including herpes zoster, chicken pox, herpes), severe coronary heart disease, myocardial infarction (history), arrhythmias.
PREGNANCY AND LACTATION
Paclitaxel-LENS is contraindicated in pregnancy and during breastfeeding.
Patients should be provided with reliable contraceptive methods during treatment with Paclitaxel-LENS and at least 3 months after the end of therapy.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution, use the drug for liver failure.
APPLICATION FOR CHILDREN
The safety and effectiveness of the use of the drug Paclitaxel-LENS in children is not established.
SPECIAL INSTRUCTIONS
The use of Paclitaxel-LENS should be performed under the supervision of a physician with experience in working with antitumor chemotherapeutic drugs.
To prevent severe hypersensitivity reactions, all patients should undergo premedication with glucocorticosteroids, antihistamines and histamine H2 blockers. In case of severe hypersensitivity reactions, the infusion of Paclitaxel-LENS should be stopped immediately and symptomatic treatment should be started, and the drug should not be reintroduced.
During treatment with the drug should regularly monitor the picture of peripheral blood, blood pressure, heart rate and the number of breaths (especially during the first hour of infusion), ECG control (and before treatment). In cases of development of violations of AV-conduction, with repeated administration it is necessary to conduct continuous cardiomonitoring.
If Paclitaxel-LENS is used in combination with cisplatin, Paclitaxel-LENS should be administered first.
Polyoxyethylated castor oil, which is part of the Paclitaxel-LENS preparation, can cause extraction of DEHP [di- (2-hexyl) phthalate] from plasticized PVC containers, and the degree of leaching of the DEHP increases with increasing solution concentration and over time. Therefore, when preparing, storing and administering Paclitaxel-LENS, you should use equipment that does not contain PVC parts.
Paclitaxel-LENS is a cytotoxic substance that should be used with caution, 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.
Use in Pediatrics
The safety and effectiveness of the use of the drug Paclitaxel-LENS in children is not established.
Impact on the ability to drive vehicles and manage mechanisms
During treatment with Paclitaxel-LENS, one should refrain from engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: bone marrow aplasia, peripheral neuropathy, mucositis.
Treatment: symptomatic. The antidote to paclitaxel is unknown.
DRUG INTERACTION
Cisplatin reduces the total clearance of paclitaxel by 20% (with more pronounced myelosuppression observed when paclitaxel is administered after cisplatin).
Simultaneous use with cimetidine, ranitidine, dexamethasone or diphenhydramine does not affect the association of paclitaxel with plasma proteins.
Inhibitors of microsomal oxidation (including ketoconazole, cimetidine, verapamil, diazepam, quinidine, cyclosporine) inhibit the metabolism of paclitaxel.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children, protected from light at a temperature of no higher than 25 В° C. Shelf life - 2 years.
