Paclitaxel-LENS - instructions for use, dose, side effects, contraindications

Excipients:
Polyoxyl 35 castor oil (macrogol glyceryl hydroxy stearate) in terms of 100% substance - 527.0 mg, ethanol (ethanol anhydrous) - up to 1 ml.

Description:

Transparent colorless or slightly yellowish viscous liquid.

Pharmacotherapeutic group:antitumor agent - alkaloid

ATX: & nbsp

L.01.C.D. Taxoids

L.01.C.D.01 Paclitaxel

Pharmacodynamics:

Paclitaxel-LENS® (paclitaxel) 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:With intravenous (IV) administration for 3 hours at a dose of 135 mg / m² the maximum concentration (Сmах) is 2170 ng / ml, the area under the curve "concentration-time" (AUC) - 7952 ng / h / ml; when the same dose was administered within 24 hours, 195 ng / ml and 6300 ng / h / ml, respectively. Stam and AUC dose-dependent: with a 3-hour infusion, increasing the dose to 175 mg / m² leads to an increase in these parameters by 68% and 89%, respectively, at 24 hours - by 87% and 26%, respectively.

The connection with plasma proteins is 88-98%. The average volume of distribution is 198-688 l / m². 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.

Metabolized in the liver by hydroxylation with the participation of cytochrome P450 isoenzymes CYP2D8 (with the formation of a metabolite - 6-alpha-hydroxypaclitaxel) and CYP3CA4 (with the formation of metabolites of 3-para-hydroxy-paclitaxel and 6-alpha, 3-para-dihydroxy paclitaxel). It is excreted mainly with bile - 90%. With repeated infusions do not cumulate.

The half-life 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 / m², respectively. After intravenous infusion (1-24 hours), the total excretion by the kidneys is 1.3-12.6% of the dose (15-275 mg / m²), which indicates the presence of intensive extrarenal clearance. The total ground clearance is 11-24 l / sq.m.

Indications:

- Ovarian cancer (first-line therapy of patients with a common form of disease or residual tumor (more than 1 cm) after laparotomy (in combination with cisplatin) and second-line therapy with metastases after standard therapy, which did not give a positive result).

- Breast cancer (the presence of affected lymph nodes after standard combination therapy (adjuvant treatment), after relapse, within 6 months after the initiation of adjuvant therapy - first-line therapy, metastatic breast cancer after ineffective standard therapy - second-line therapy).

- Non-small cell lung cancer (first-line therapy for patients who do not plan for 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 and lactation.

- The initial content of neutrophils is less than 1500 / μl in patients with solid tumors.

- The initial (or registered in the treatment) neutrophil count 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 herpes zoster, chicken pox, herpes), severe course of coronary heart disease, myocardial infarction (in the anamnesis), arrhythmia.

Application in pediatrics. The safety and efficacy of Paclitaxel-LENS® in children have not been established.

Dosing and Administration:

To prevent severe hypersensitivity reactions, all patients should undergo premedication with glucocorticosteroids, antihistamines and H antagonists₂-gistaminovyh receptors. For example, 20 mg dexamethasone (or its equivalent) orally approximately 12 and 6 hours before the administration of the Paclitaxel-LENS® preparation, 50 mg of diphenhydramine (or its equivalent) intravenously and 300 mg of cimetidine or 50 mg of ranitidine intravenously 30 to 60 minutes before administration preparation of Paclitaxel-LENS®.

When choosing the regimen and doses in each individual case, one should be guided by the literature data.

Paclitaxel-LENS® is 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 in the form of 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 in the form of 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 of blood and the platelet count is at least 100,000 / μL of blood. Patients who had severe neutropenia after administration of Paclitaxel-LENS® (neutrophil count <500 / mm³ blood for 7 days or longer) or a severe form of peripheral neuropathy during subsequent courses of treatment, the dose of Paclitaxel-LENS® should be reduced by 20%.

The drug solution is prepared immediately prior to administration,spreading the concentrate 0.9% sodium chloride or 5% dextrose, or 5% dextrose in 0.9% sodium chloride solution for injection or 5% dextrose 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®, use equipment that does not contain PVC parts.

Paclitaxel-LENS® should be introduced through a system with an integrated membrane filter (pore size not more than 0.22 microns).

Side effects:

The frequency and severity of side effects are dose-dependent.

From the hematopoiesis: neutropenia, thrombocytopenia, anemia.

Suppression of bone marrow function, mainly granulocyte germ, was the main toxic effect that limits 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.

Allergic reactions: in the first hours after the administration of Paclitaxel-LENS®, there may be reactions of hypersensitivity, manifested by bronchospasm, lowering blood pressure, pain behind the sternum, flushing of the face, skin rashes, generalized urticaria, angioneurotic edema. Single cases of chills and pains in the back are described.

From the cardiovascular system: lowering blood pressure, less often - raising blood pressure, bradycardia, tachycardia, atrioventricular blockade, ECG changes, vascular thrombosis and thrombophlebitis are possible.

From the respiratory system: interstitial pneumonia, pulmonary fibrosis, pulmonary embolism, and more frequent development of radiation pneumonitis in patients concomitant with radiotherapy.

From the nervous system: mainly paresthesia. Rarely - convulsive seizures of the type grand mal, visual impairment, ataxia, encephalopathy, vegetative neuropathy, manifested by paralytic intestinal obstruction and orthostatic hypotension.

From the musculoskeletal system: arthralgia, myalgia.

From the digestive system: nausea, vomiting, diarrhea, mucositis, anorexia, constipation.Single reports of acute intestinal obstruction, perforation of the intestine, thrombosis of the mesenteric artery, ischemic colitis.

On the part of the liver: increased activity of "liver" transaminases (more often ACT), alkaline phosphatase and bilirubin in serum. The cases of development of hepatonecrosis and hepatic encephalopathy are described.

Local reactions: pain, swelling, erythema, induration and skin pigmentation at the injection site; Extravasation can cause inflammation and necrosis of subcutaneous tissue.

From the skin and skin appendages: alopecia, rarely a violation of pigmentation or discoloration of the nail bed.

Other adverse reactions: asthenia and general malaise.

Overdose:

Symptoms: aplasia of the bone marrow, peripheral neuropathy, mucositis. Treatment: symptomatic. The antidote to paclitaxel is not known.

Interaction:

Cisplatin reduces the total clearance of paclitaxel by 20% (with more pronounced myelosuppression observed when paclitaxel injected after cisplatin). Simultaneous administration with cimetidine, ranitidine, dexamethasone or difengi drams does not affect the association of paclitaxel with plasma proteins.

Inhibitors of microsomal oxidation (incl. ketoconazole, cimetidine, verapamil, diazepam, quinidine, ciclosporin and others) suppress the metabolism of paclitaxel.

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 H antagonists2 histamine receptors: 20 mg of dexamethasone (or its equivalent) orally within 12 and 6 hours prior to administration of Paclitaxel-LENS®, 50 mg of diphenhydramine (or its equivalent) intravenously and 300 mg of cimetidine or 50 mg of ranitidine intravenously 30 to 60 minutes before administration Paclitaxel-LENS®.

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 re-administered.

Polyoxyethylated castor oil, which is part of the preparation Paclitaxel-LENS®,can cause the extraction of DEHP [di- (2-hexyl) phthalate] from plasticized polyvinylchloride (PVC) containers, the degree of leaching of the DEHP increases with increasing solution concentration and with time. Therefore, when preparing, storing and administering Paclitaxel-LENS®, 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), ECG control (and before treatment).

In cases of development of violations of atrioventricular conduction, with repeated administration it is necessary to carry out continuous cardiomonitoring.

If Paclitaxel-LENS® is used in combination with cisplatin, Paclitaxel-LENS® should first be administered, and then cisplatin.

Patients should be provided with reliable contraceptive methods during treatment with Paclitaxel-LENS® and at least 3 months after the end of therapy.

During the treatment period, it is necessary to refrain from engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

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.

Form release / dosage:Concentrate for the preparation of a solution for infusion 6 mg / ml (30 mg / 5 ml 100 mg / 17 ml, 120 mg / 20 ml, 140 mg / 23.3 ml, 150 mg / 25 ml, 210 mg / 35 ml 250 mg / 41.7 ml, 260 mg / 43.4 ml, 276 mg / 46 ml, 300 mg / 50 ml).

Packaging:5 ml, 17 ml, 20 ml, 23.3 ml, 25 ml, 35 ml, 41.7 ml, 43.4 ml, 46 ml or 50 ml in neutral glass bottles. hermetically sealed with stoppers of bromobutyl rubber with an internal inert fluoropolymer coating, with a roll of aluminum-plastic caps.

For 1 bottle with instructions for use in a pack of cardboard.

1 bottle with instructions for use in a pack of cardboard, complete with an infusion system with an integrated membrane filter with a pore diameter of no more than 0.22 microns, not containing parts from the PBX.

For 30, 50, 72 or 100 bottles with an equal number of instructions for use are placed in a box of cardboard (for hospitals).

For 30, 50, 72 or 100 vials in a complete set with an equal number of infusion systems with a built-in membrane filter with a pore diameter of no more than 0.22 microns.not containing parts from PVC and with an equal number of instructions for use in a box of cardboard (for hospitals).

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

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:P N000006 / 01

Date of registration:13.12.2011

The owner of the registration certificate:LENS-PHARM, LLC LENS-PHARM, LLC Russia

Manufacturer: & nbsp

LENS-PHARM, LLC Russia

Information update date: & nbsp11.10.2015

Illustrated instructions

Instructions

Paclitaxel-LENS® (Paclitaxel-LANS)