Composition, form of production and packaging
Concentrate for the preparation of solution for infusions in the form of a transparent, yellowish solution, without visible mechanical inclusions.
1 ml of 1 fl.
paclitaxel 6 mg 30 mg
Excipients: citric acid anhydrous, ethanol, castor oil, polyoxylated.
5 ml - bottles (1) - packs of cardboard.
Concentrate for the preparation of solution for infusions in the form of a transparent, yellowish solution, without visible mechanical inclusions.
1 ml of 1 fl.
paclitaxel 6 mg 100 mg
Excipients: citric acid anhydrous, ethanol, castor oil, polyoxylated.
16.7 ml - vials (1) - packs of cardboard.
Concentrate for the preparation of solution for infusions in the form of a transparent, yellowish solution, without visible mechanical inclusions.
1 ml of 1 fl.
paclitaxel 6 mg 150 mg
Excipients: citric acid anhydrous, ethanol, castor oil, polyoxylated.
25 ml - bottles (1) - packs of cardboard.
Concentrate for the preparation of solution for infusions in the form of a transparent, yellowish solution, without visible mechanical inclusions.
1 ml of 1 fl.
paclitaxel 6 mg 300 mg
Excipients: citric acid anhydrous, ethanol, castor oil, polyoxylated.
50 ml - bottles (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2005.
PHARMACHOLOGIC EFFECT
An antineoplastic preparation of natural origin, obtained semisynthetic way 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.
In experimental studies , it has been shown that paclitaxel has mutagenic and embryotoxic properties, causing a deterioration in reproductive function.
PHARMACOKINETICS
Suction
With iv administration of Paxen at a dose of 135 mg / m 2 for 3 h C max paclitaxel in blood plasma is 2170 ng / ml, AUC is 7952 ng / h / ml; with the same dose administered for 24 hours - 195 ng / ml and 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%. The average V d is 198-688 l / m 2 . The time of half-distribution from the blood in the tissue is 30 minutes. Easily penetrates into tissues, accumulates mainly in the liver, spleen, pancreas, stomach, intestines, heart, muscles.
Metabolism
It is metabolized in the liver by hydroxylation with the participation of cytochrome P 450 CYP2D8 isoenzymes (with the formation of metabolite - 6-alpha-hydroxypaclitaxel) and CYP3A4 (with the formation of metabolites 3-para-hydroxypaclitaxel and 6-alpha, 3 para-dihydroxy-paclitaxel).
Excretion
It is excreted mainly with bile - 90%. With repeated infusions do not cumulate.
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 / m 2 .
INDICATIONS
ovarian cancer (first-line therapy for patients with a common form of disease or residual tumor (more than 1 cm) after laparotomy (in combination with cisplatin) and second-line therapy for metastases after standard therapy that did not work well;
- 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 surgical treatment and / or radiation therapy);
Kaposi's commissar in AIDS patients (second-line therapy, after ineffective therapy with liposomal anthracyclines).
DOSING MODE
To prevent severe hypersensitivity reactions, all patients should undergo premedication with the use of GCS, antihistamines and blockers of histamine H2-receptors.For example, 20 mg of dexamethasone (or its equivalent) orally for about 12 hours and 6 hours before the administration of Paxen, 50 mg of diphenhydramine (or its equivalent) IV and 300 mg of cimetidine or 50 mg of ranitidine IV for 30-60 minutes before introduction of Paxen.
Paxen is administered iv in a dose of 135-175 mg / m 2 as a 3-hour or 24-hour infusion, 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 Paxen for the treatment of Kaposi's sarcoma in AIDS patients is 100 mg / m 2 as a 3-hour infusion every 2 weeks.
When choosing the regimen and doses in each individual case, one should be guided by the literature data.
The introduction of Paxel should not be repeated until the neutrophil count in peripheral blood is at least 1500 / Ојl and the platelet count is at least 100,000 / ОјL.Patients who experienced severe neutropenia (neutrophil count <500 / ОјL for 7 days or longer) or severe form of peripheral neuropathy after Paxen administration, should be reduced by 20% during subsequent courses of treatment.
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 0.9% sodium chloride solution d / and 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 introducing Paxena, you should use equipment that does not contain PVC parts.
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 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.
Allergic reactions: in the first hours after Paxen's administration, bronchospasm, lowering of blood pressure, chest pain, flushing to the face, skin rashes, generalized urticaria, angioedema may be possible. Single cases of chills and back pain are described.
From the side of the cardiovascular system: a decrease in blood pressure, tachycardia, AV blockade, changes in ECG, vascular thrombosis and thrombophlebitis arepossible; rarely - increased blood pressure, bradycardia.
On the part of the respiratory system: interstitial pneumonia, pulmonary fibrosis, pulmonary embolism, as well as more frequent development of radiation pneumonitis in patients concurrent with radiotherapy are possible.
From the central nervous system and peripheral nervous system: paresthesia is possible; rarely convulsive seizures such as grand mal, visual impairment, ataxia, encephalopathy, autonomic neuropathy, manifested by paralytic intestinal obstruction and orthostatic hypotension.
From the musculoskeletal system: possible arthralgia, myalgia.
On the part of the digestive system: nausea, vomiting, diarrhea, mucositis, anorexia, constipation; increased activity of hepatic transaminases (more often AST), APF and bilirubin in blood serum; in isolated cases - acute intestinal obstruction, intestinal perforation, mesenteric artery thrombosis, ischemic colitis, hepatonecrosis, hepatic encephalopathy.
Dermatological reactions: alopecia, rarely - a violation of pigmentation or discoloration of the nail bed.
Local reactions: 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.
CONTRAINDICATIONS
- the initial content of neutrophils is less than 1500 / ОјL in patients with solid tumors;
-initial (or recorded during treatment) neutrophil count less than 1000 / Ојl in patients with Kaposi's sarcoma in AIDS patients;
-pregnancy;
-lactation (breastfeeding);
-increased sensitivity to the drug, as well as other drugs, the dosage form of which includes polyoxylated castor oil.
With caution in patients with thrombocytopenia (less than 100 000 / Ојl), liver failure, acute infectious diseases (including shingles, chicken pox, herpes), severe coronary heart disease, myocardial infarction (history), arrhythmias.
The safety and effectiveness of Paxen in children is not established.
PREGNANCY AND LACTATION
Paxen is contraindicated in pregnancy and lactation (breastfeeding).
Patients of reproductive age during treatment with Paxen and, at least 3 months after the end of therapy should use reliable methods of contraception.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution in liver failure.
APPLICATION FOR CHILDREN
The safety and effectiveness of Paxen in children is not established.
SPECIAL INSTRUCTIONS
Treatment Paxen should be conducted under the supervision of a doctor who has experience with antitumor chemotherapeutic drugs.
To prevent severe hypersensitivity reactions, all patients should be premedicated using GCS, antihistamines and histamine H2-blockers: 20 mg dexamethasone (or its equivalent) orally for about 12 hours and 6 hours before administration of Paxen, 50 mg of diphenhydramine (or its equivalent) IV and 300 mg of cimetidine or 50 mg of ranitidine IV for 30-60 minutes before the administration of Paxen.
In case of severe hypersensitivity reactions, the infusion of Paxen should be stopped immediately and symptomatic treatment should be started, and the drug should not be re-administered.
During treatment, it is necessary to regularly monitor the picture of peripheral blood, blood pressure, heart rate and BH (especially during the first hour of infusion), ECG control (and before treatment).
In cases of development of AV conduction disorders with repeated administration, continuous cardiomonitoring is necessary.
When used in combination with cisplatin, Paxen should first be administered, followed by cisplatin.
Polyoxyethylated castor oil, which is part of the Paxen preparation, can cause extraction of DEHP / di- (2-hexyl) phthalate / from plastic PVC containers, where the degree of leaching of the DEHP increases with increasing solution concentration and over time. Therefore, when preparing, storing and injecting a solution of Paxen, use equipment that does not contain PVC parts.
Paxen 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.
Impact on the ability to drive vehicles and manage mechanisms
During the treatment period, it is necessary to refrain from engaging in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: aplasia of the braincase, peripheral neuropathy, mucositis.
Treatment: symptomatic therapy. The antidote 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 administration with cimetidine, ranitidine, dexamethasone or diphenhydramine does not affect the association of paclitaxel with plasma proteins.
Inhibitors of microsomal oxidation (including ketoconazole, cimetidine, dexamethasone, verapamil, diazepam, quinidine, cyclosporine) inhibit the metabolism of paclitaxel. This interaction with the administration of drugs in therapeutic doses has no clinical significance.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a place protected from light, inaccessible to children at a temperature of 10 В° to 25 В° C. Shelf life - 3 years.
