Abitaxel - instructions for use, dose, side effects, contraindications

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 maximum concentration (Сmah) 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.

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.

Metabol is excreted 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 3-para-hydroxypaclitaxel and 6-alpha, 3-parahydroxy-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.

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).

- Sarcoma Kalosha patients with AIDS (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.

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 .

The safety and effectiveness of the drug Abitaxel in children is not established.

Dosing and Administration:

To prevent severe reactions of hypersensitivity, all patients should undergo premedication with glucocorticosteroids, antihistamines and H2-histamine receptor antagonists. For example, 20 mg of dexamethasone (or its equivalent) orally within 12 and 6 hours before the administration of the drug Abitaxel, 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 the drug Abitaxel.

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

Abitaxel is administered intravenously in the form of a 3-hour or 24-hour infusion in a dose 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 the drug Abitaxel 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 the drug Abitaxel 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 with severe neutropenia (neutrophil count <500 / μL blood for 7 days or longer) or severe peripheral neuropathy after the administration of Abitaxel should be reduced by 20% during subsequent courses of treatment.

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 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 the drug, Abitaxel should use equipment that does not contain PVC parts.

Abitaxel should be administered 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 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 immune system: In the first hours after the administration of Abitaxel, hypersensitivity reactions may occur,manifested bronhospazmom, lowering blood pressure, pain in the chest, flushing 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 (BP), 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 pneumonics in patients undergoing 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.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 bilirubin in serum. 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, swelling, 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).

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 diphenhydramine 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. Polyoxyethylated castor oil, which is a part of paclitaxel, can cause 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.

Special instructions:

The use of abitaxel should be carried out under the supervision of a doctor who has experience with antitumor chemotherapeutic drugs.

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

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 Abitaxel and, at least 3 months after the end of therapy.

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.

Abitaxel 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 infusions of 6 mg / ml.

Packaging:

For 30 mg / 5 ml, 100 mg / 16.7 ml, 150 mg / 25 ml, 210 mg / 35 ml and 300 mg / 50 ml in colorless glass bottles sealed with a chlorobutyl stopper and crimped with an aluminum cap with a plastic insert "Flip off".

1 bottle with instructions for use in a cardboard pack.

Storage conditions:

List B.

At a temperature of 15 - 25 ° C in the dark place.

Keep out of the reach of children.

Shelf life:

3 years.

The drug should not be used after the expiry date indicated on the package. The dilute solutions of Abitaxel are stable at room temperature for 27 hours.

Terms of leave from pharmacies:On prescription

Registration number:П N015865 / 01

Date of registration:27.04.2009

Expiration Date:Unlimited

The owner of the registration certificate:Laboratory Tutor SAASIFAALaboratory Tutor SAASIFAA Argentina

Manufacturer: & nbsp

Laboratorio TUTEUR S.A.C.I.F.I.A. Argentina

Representation: & nbspHEAD OF MEDICA SAHEAD OF MEDICA SASwitzerland

Information update date: & nbsp17.01.2017

Illustrated instructions

Instructions

Abitaxel (Abitaxel)