Index of drugs

Ovarian cancer. As a first line treatment in combination with Cisplatin in the treatment of patients with advanced or residual form (> 1 cm) of cancer after previous laparotomy. As a second-line treatment for the treatment of metastatic ovarian tumors in cases where standard treatment with platinum was ineffective.Breast cancer. Supplementary treatment of breast cancer in patients with lymph node involvement after standard multidrug therapy containing anthracycline and cyclophosphamide - AC (adjuvant treatment should be considered as an alternative to prolonged AC therapy). First-line treatment of locally advanced or metastatic breast cancer, both in combination with anthracyclines in patients who can be treated with anthracyclines and in combination with trastuzumab in patients with increased 2 (HER-2) level expression at level 3+ as determined in the study immunohistochemistry in which treatment with anthracyclines is not suitable. Monotherapy with metastatic breast cancer in patients whose standard anthracycline therapy has not improved or could not be used.An advanced form of non-small cell lung cancer. Treatment of non-small cell lung cancer in combination with cisplatin in patients who can not be treated with radical surgery and / or radiotherapy.Kaposi's sarcoma in the course of AIDS. Treatment of advanced Kaposi's sarcoma occurring in the course of AIDS in patients in whom treatment with liposomal anthracyclines was ineffective (a small number of data confirms the efficacy of Paclitaxel in the above indication).

1 vial contains 30 mg, 100 mg or 300 mg paclitaxel (1 ml concentrate for solution for infusion contains 6 mg paclitaxel); drug contains ethanol and macrogolglycerol ricinoleate.

An anti-cancer drug. Paclitaxel promotes the formation of microtubules from tubulin dimers and stabilizes them, preventing depolymerization. The result of this action is the inhibition of the reorganization of the microtubule network necessary for basic cell functions related to mitotic division and interphase. In addition, paclitaxel causes the formation of abnormal aggregates or microtubule bundles during the cell cycle and the formation of multiple spindles during mitosis. After intravenous administration, paclitaxel shows a two-phase decrease in blood levels. At doses of 135 mg and 175 mg / m² pc. in a 3- or 24-hour infusion, the mean terminal half-life was 3-5.7 h. The degree of binding to plasma proteins is 89-98%. Hepatic metabolism (involving the cytochrome P-450 enzyme system, mainly CYP2C8, CYP3A4) and biliary secretion may be considered the main route of paclitaxel elimination.

Increased hypersensitivity to paclitaxel or any of the other ingredients (especially macrogolglycerol ricinoleate). Neutrophil count <1500 / mm³ or the number of plates <100,000 / mm³ (in patients with Kaposi's sarcoma: <1000 / mm³ and <75,000 / mm³). Severe non-treatable infection (concerns the treatment of patients with Kaposi's sarcoma). Pregnancy and breastfeeding.

The drug should not be administered intra-arterially. Due to the possibility of severe hypersensitivity reactions after administration of the drug, appropriate measures and equipment should be provided to enable intensive therapy. If hypersensitivity reactions occur, the paclitaxel infusion should be stopped immediately and symptomatic treatment initiated; do not try to continue to administer the medicine to your patient. During treatment, check the blood image regularly. During clinical trials, the majority of patients with Kaposi's sarcoma received a granulocyte growth factor (G-CSF). Regular monitoring of vital signs is recommended, especially during the first hour of paclitaxel infusion. If cardiac conduction abnormalities develop during paclitaxel therapy, appropriate symptomatic treatment should be initiated and continued monitoring of cardiac function during subsequent courses of treatment. Due to the increased risk of cardiotoscopy, a cardiac examination should be performed prior to initiating combination therapy with doxorubicin or trastuzumab: collect an accurate history of cardiac function assessment, physical examination, electrocardiogram, echocardiogram and / or MUGA isotopic scintigraphy; during treatment (eg every 3 months) heart function should be monitored.The cumulative dose (mg / m) should also be determined exactly² pc.) of an anthracycline, deciding on the frequency of cardiac ventricular function evaluation. If the results of cardiac functional examinations show worsening of his work, even asymptomatic, consideration should be given to the clinical benefits resulting from further treatment in terms of possible heart damage, including potentially irreversible damage. If treatment is continued, the heart should be monitored more frequently (eg every 1-2 courses of treatment). Exercise caution in patients with hepatic impairment; observe whether myelotoxicity is worsening. There are no data on patients with initial severe hepatic cholestasis. Paclitaxel is not recommended for patients with severe hepatic impairment. If severe or persistent diarrhea is observed during or shortly after treatment, pseudomembranous colitis should be considered. Patients during treatment should use measures to protect their hands and feet from solar radiation. Since the preparation contains ethanol, the possibility of alcohol influence on o.u.n. and other effects of its operation. Due to the content of macrogolglycerol ricinoleate, the drug may cause severe hypersensitivity reactions.

Paclitaxel is teratogenic, embryotoxic and mutagenic. The drug is contraindicated during pregnancy and breastfeeding. Women of childbearing age and men must use effective contraception during treatment with paclitaxel and for 6 months after its completion. Before starting treatment, the patient should be informed about the possibility of freezing sperm due to the possibility of irreversible infertility due to paclitaxel treatment.

Side effects after paclitaxel monotherapy infused over 3 hours in the treatment of metastatic lesions and side effects from post-marketing reports. Very common: infections (especially of the urinary tract and upper respiratory tract), bone marrow suppression, neutropenia, anemia, thrombocytopenia, leukopenia, bleeding, mild hypersensitivity reactions (mainly redness and rash), neurotoxicity (mainly peripheral neuropathy), hypotension, nausea, vomiting, diarrhea, mucositis, alopecia, joint and muscle pain. Common: bradycardia, transient mild changes in the skin and nails, reactions at the injection site (swelling, pain, erythema), hardening at the injection site, inflammation of the subcutaneous tissue (when administered outside the vein), significant elevation of aminotransferases. Uncommon: septic shock, severe hypersensitivity reactions requiring treatment (eg: hypotension, angioneurotic edema, impaired breathing, generalized urticaria, chills, back pain, chest pain, tachycardia, abdominal pain, limb pain, profuse sweating and hypertension) , cardiomyopathy, asymptomatic ventricular tachycardia, twin-saturable tachycardia, atrio-ventricular block with syncope, myocardial infarction, hypertension, thrombosis, thrombophlebitis, a significant increase in bilirubin. Rarely: pneumonia, peritonitis, sepsis, neutropenic fever, anaphylactic reactions, motor neuropathy (with mild peripheral weakness), dyspnea, pleural effusion, interstitial pneumonitis, pulmonary embolism, respiratory failure, intestinal obstruction, intestinal perforation, ischemic colitis, pancreatitis, pruritus, rash, erythema, weakness, fever, dehydration, edema, malaise, increase in creatinine. Very rare: acute myelogenous leukemia, myelodysplastic syndrome, anaphylactic shock, anorexia, confusion, neuropathy of autonomic nerves (leading to paralytic ileus and orthostatic hypotension), grand mal convulsions, convulsions, encephalopathy, dizziness, headache, ataxia, function of the optic nerve and / or vision (flashing scots, especially in patients receiving higher doses than recommended), ototoxicity, hearing loss, tinnitus, dizziness, atrial fibrillation, supraventricular tachycardia, shock, cough, mesenteric thrombosis pseudomembranous colitis, esophagitis, constipation, ascites, hepatic necrosis and hepatic encephalopathy (both cases were reported fatal), Stevens-Johnson syndrome, toxic epidermal necrolysis,erythema multiforme, exfoliative dermatitis, urticaria, separation of the nail from the placenta. Skin necrosis and / or skin exfoliation, sometimes caused by extravasation, have been reported. Skin discoloration may also occur. Secondary skin lesions at the site of previous extravasation have been observed rarely after subsequent doses of paclitaxel elsewhere. In patients treated with paclitaxel followed by Cisplatin, an increased incidence of serious neurotoxicity was observed. In the case of combination therapy with doxorubicin, cardiac contractility disorders have been reported. Administration of trastuzumab in combination with paclitaxel in patients previously treated with anthracyclines resulted in an increase in the incidence and severity of heart failure compared to paclitaxel monotherapy; in a few cases deaths have been observed. In patients treated with paclitaxel and undergoing radiation therapy, radiation pneumonia was reported. The following disorders were more common in the treatment of metastatic breast cancer using a 3-hour infusion of paclitaxel in combination with trastuzumab, as the first-line treatment than paclitaxel monotherapy: circulatory insufficiency, infection, chills, fever, cough, rash, joint pain , tachycardia, diarrhea, hypertension, epistaxis, acne, herpes, accidental injuries, insomnia, rhinitis, sinus inflammation, infection at the injection site. In patients with Kaposi's sarcoma in the course of AIDS, it was observed that with the exception of hematopoietic system disorders and hepatopathy, the frequency and severity of adverse reactions were comparable, as in patients treated with paclitaxel monotherapy for other solid tumors.

The drug should be administered under the supervision of a qualified doctor who has experience in conducting anti-cancer chemotherapy. Before starting to use Paclitaxel, premedication should be used consisting of: corticosteroid - Dexamethasone 20 mg (8-20 mg in patients with Kaposi's sarcoma) orally 12 and 6 hours before the infusion is started or intravenously 30 to 60 minutes before the infusion begins; antihistamine - diphenhydramine 50 mg (or other antihistamine) intravenously 30 to 60 minutes before the start of the infusion; H receptor antagonists₂ - cimetidine 300 mg intravenously or Ranitidine 50 mg intravenously 30 to 60 minutes before the start of the infusion.Ovarian cancer. Treatment of ovarian cancer with the use of paclitaxel as a first-line drug: paclitaxel at a dose of 160 mg / m² pc. in a 3-hour intravenous infusion (or at a dose of 135 mg / m² pc. in a 24-hour infusion) followed by cisplatin 75 mg / m² pc, with a 3-week break between successive courses of treatment. Treatment of ovarian cancer with paclitaxel as a second-line treatment: paclitaxel at a dose of 175 mg / m² pc. in a 3-hour intravenous infusion, with a 3-week break between successive courses of treatment.Breast cancer. Supplementary treatment for breast cancer: paclitaxel at a dose of 175 mg / m² pc. in a 3-hour intravenous infusion, every 3 weeks, after multidrug therapy containing anthracycline and cyclophosphamide (AC); treatment should include 4 courses of paclitaxel administration. Treatment of breast cancer with paclitaxel as a first line treatment: paclitaxel at a dose of 220 mg / m² pc. in a 3-hour intravenous infusion 24 hours after doxorubicin 50 mg / m² pc, with a 3-week break between successive courses of treatment. In combination with trastuzumab, a paclitaxel dose of 175 mg / m is recommended² pc. in a 3-hour intravenous infusion, with a 3-week break between courses (paclitaxel may be administered the Next day after the first dose of trastuzumab or immediately after subsequent doses if the previous dose of trastuzumab was well tolerated; details on the dose of trastuzumab are included in the Product Characteristics Medicinal for trastuzumab). Treatment of breast cancer with paclitaxel as a second-line treatment: paclitaxel at a dose of 175 mg / m² pc. in a 3-hour intravenous infusion, with a 3-week break between successive courses of treatment.An advanced form of non-small cell lung cancer: paclitaxel at a dose of 175 mg / m² pc. in a 3-hour intravenous infusion followed by cisplatin 80 mg / m² pc, with a 3-week break between successive courses of treatment.Kaposi's sarcoma in the course of AIDS: paclitaxel 100 mg / m² pc. in a 3-hour intravenous infusion, with a 2-week break between consecutive courses of treatment.Dose adjustment. Paclitaxel should not be re-administered until the neutrophil count reaches ≥ 1500 / mm³ (in patients with Kaposi's sarcoma ≥1000 / mm³), and platelet count value ≥100,000 / mm³ (in patients with Kaposi's sarcoma ≥75.000 / mm³). In patients with severe neutropenia (neutrophil count <500 / mm³ persisting for 7 days or longer) or increased peripheral neuropathy, paclitaxel doses should be reduced in subsequent treatment cycles by 20% (in patients with Kaposi's sarcoma by 25%). In case of severe mucositis in patients with Kaposi's sarcoma, the dose of paclitaxel should be reduced by 25%.Special groups of patients. There is insufficient data to suggest dose changes in patients with mild to moderate hepatic impairment; Do not use in patients with severe hepatic impairment.
The drug should be administered through an infusion set with an internal filter containing a micropore membrane with a diameter of ≤ 0.22 μm. Macrogol glycerol ricinoleate contained in the preparation may cause DEHP leaching from PVC containers, in quantities increasing over time and with increasing drug concentration - the preparation, storage and administration of the drug should be carried out using equipment that does not contain PVC.