Kanataksen - instructions for use, doses, side effects, contraindications

Kanataksen® (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; with the same dose administered for 24 hours at 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.

Communication 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 CYP2C8 (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-paradihydroxy 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 introduction: 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.

Indications:

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

- Breast cancer (the presence of affected lymph nodes after standard combination therapy (adjuvant treatment), after relapse, within 6 months after 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 surgical treatment and / or radiation therapy (in combination with cisplatin).

- Kaposi's Sarcoma in AIDS patients (second-line therapy).

Contraindications:

- Hypersensitivity to paclitaxel or other constituents of the drug (including polyoxyethylated castor oil)

- 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.

- Pregnancy and lactation.

- Child age (safety and efficacy not established)

Carefully:

Inhibition of bone marrow hemopoiesis (including after chemotherapy or radiation therapy), liver failure, acute infectious diseases (including herpes zoster, chickenpox, herpes), severe course of coronary heart disease, myocardial infarction (history), arrhythmias .

Dosing and Administration:

To prevent severe hypersensitivity reactions, all patients should undergo premedication with glucocorticosteroids, H1 and H2-histamine receptor blockers. For example, 20 mg of dexamethasone (or its equivalent) is administered approximately 12 and 6 hours before the administration of Kanataksen®, 50 mg of diphenhydramine (or its equivalent) intravenously and 300 mg of cimetidine or 50 mg of ranitidine intravenously 30 to 60 minutes before the administration of Kanataxen ®.

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

Kanataksen® is administered intravenously as a 3-hour or 24-hour infusion at a dose of 175 mg / m² or 135 mg / m² with an interval between administrations 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 Kanataksen® for the treatment of Kaposi's sarcoma in AIDS patients is 100 mg / m² in the form of a 3-hour infusion every 2 weeks.

The administration of Kanataksen® 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 have been treated with Kanataksen®. Severe neutropenia (neutrophil count <500 / μL blood for 7 days or longer) or severe peripheral neuropathy, in a subsequent course of treatment, the dose of Kanataksen® should be reduced by 20%.

Solution for infusion 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 the final concentration from 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 the Kanataksen® preparation, you should use equipment that does not contain parts made of polyvinyl chloride (PVC).

Kanataksen® should be introduced through a system with an integrated membrane filter (pore diameter not more than 0.22 microns).

If unopened vials are placed in the refrigerator, a precipitate may form which dissolves again with little stirring (or without stirring) when room temperature is reached. The quality of the product does not deteriorate. If the solution remains cloudy, or if there is an insoluble deposit, the vial should be destroyed.

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 limiting the dose of the drug.The maximum decrease in the number of neutrophils is usually observed on day 8-11, normalization occurs on day 22.

From the immune system: in the first hours after the administration of the drug Kanataksen®, there may be reactions of hypersensitivity, manifested by bronchospasm, lowering of arterial pressure (BP), pains in the chest area, "tides" of blood to the face, skin rashes, generalized urticaria, angioedema. 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, rhythm disturbance, atrioventricular blockade, ventricular bigemini, changes in ECG, thrombosis of venous vessels 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, autonomic 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. There are isolated reports of acute intestinal obstruction, intestinal perforation, mesenteric artery thrombosis, ischemic colitis.

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

From the skin and skin appendages: alopecia, rarely a violation of pigmentation or discoloration of the nail bed. Very rarely - multiforme exudative erythema, incl. Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, onycholysis.

From the sense organs: decreased visual acuity, conjunctivitis, increased lacrimation.

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

Other: asthenia and general malaise, decreased tolerance to infections (any etiology), flu-like syndrome, malaise, chest pain, chills, fever, dehydration, decreased or weight gain, severe infections, septic shock.

Overdose:

Symptoms: bone marrow aplasia, peripheral neuropathy, mucositis.

Treatment: symptomatic. The antidote to paclitaxel is not known.

Interaction:

When paclitaxel is administered after cisplatin, paclitaxel clearance is reduced by approximately 33%, with more pronounced myelosuppression, cisplatin it is recommended to administer after paclitaxel.

Simultaneous administration with cimetidine, ranitidine, dexamethasone or diphenhydramine does not affect the association of paclitaxel with plasma proteins.

With the use of paclitaxel in combination with doxorubicin, an increase in the content of doxorubicin and its active metabolite of doxorubicin in blood plasma can be observed.

Paclitaxel is metabolized with the participation of isoenzymes CYP2C8 and CYP3A4 cytochrome P450, therefore caution should be exercised when paclitaxel and known inducers are used simultaneously (for example, rifampicin, carbamazepine, phenytoin, efavnrenz, nevirapine) or inhibitors (e.g., erythromycin, fluoxetine, gemfibrozil) of these isoenzymes.

Polyoxyethylated castor oil, which is part of paclitaxel,can cause the extraction of DEHP [di- (2-diethylhexyl) phthalate] from plasticized polyvinyl chloride (PVC) containers, where the degree of leaching of DEHP increases with increasing solution concentration and over time.

Special instructions:

Treatment with Kanataksen® should be performed under the supervision of a doctor who has experience with antitumor chemotherapeutic drugs.

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

In case of severe hypersensitivity reactions, the infusion of Kanataksen® should be stopped immediately and symptomatic treatment should be started, and the drug should not be injected again.

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.

Patients should be provided with reliable contraceptive methods during treatment with Kanataksen® and at least 3 months after the end of therapy. Kanataksen® is a cytotoxic substance that should be used with care, 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.

Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving vehicles to engage in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Concentrate for the preparation of a solution for infusions of 6 mg / ml.

Packaging:

At 30 mg / 5 ml, 100 mg / 16.7 ml or 300 mg / 50 ml in vials of colorless glass, sealed with a rubber lid, rolled with an aluminum cap and closed with a plastic cover to control the first opening.

1 or 10 bottles of 5 ml, 1 or 5 bottles of 16.7 ml and 1 or 4 bottles of 50 ml, along with instructions for use in a cardboard pack.

Storage conditions:

List B.

At a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2,5 years - bottles of 5 ml.

2 year - vials of 16,7 ml and 50 ml.

The drug should not be used after the expiry date indicated on the package. Kanataksen® solutions obtained after dilution are stable at room temperature for 27 hours.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006247/10

Date of registration:01.07.2010

Expiration Date:Unlimited

The owner of the registration certificate: Genfa Medica S.A. Genfa Medica S.A. Switzerland

Manufacturer: & nbsp

GENFA MEDICA, S.A. Canada

Representation: & nbspHEAD OF MEDICA SAHEAD OF MEDICA SASwitzerland

Information update date: & nbsp22.11.2017

Illustrated instructions

Instructions

Kanataxen (Kanataxene)