2010/06/05

Paclitaxel

International name:
Paclitaxel (Paclitaxel)

Group Affiliation:
Antitumor agents, alkaloid

Description of the active substance (INN):
Paclitaxel

Dosage form:
Concentrate for solution for infusion

Mode of action:
Antitumor agents of plant origin. Does the process of cell division, changes the process of formation and stabilization of the mitotic spindle microtubules and prevents depolymerization. As a result, suppressed the dynamic reorganization mikrotubulyarnoy network in the interphase of mitosis, causes the appearance of abnormal bundles of microtubules throughout the cell cycle and multiple condensations of star (Astaire) during mitosis.

Indications:
Ovarian cancer (first-line treatment of patients with common form of the disease or residual tumor (more than 1 cm) after laparotomy (in combination with cisplatin) and second-line therapy for metastases after conventional therapy, which gave no positive result.) Breast cancer (presence of affected lymph nodes after standard combination therapy (adjuvant therapy) after disease recurrence within 6 months after the start of adjuvant therapy - first-line therapy, metastatic breast cancer after standard therapy is ineffective - for second-line therapy). non small cell lung lung cancer (first-line treatment of patients which is not planned for surgical treatment and / or radiation therapy (in combination with cisplatin). Kaposi's sarcoma in AIDS patients: secondary treatment. Squamous cell carcinoma of the head and neck; transitorial bladder cancer, esophagus cancer, leukemia (lymphocytic, nelimfotsitarnaya).

Contraindications:
Hypersensitivity (including to polioksolu castor oil), neutropenia (less than 1.5 thousand / ml), thrombocytopenia (less than 100 thousand / ml), pregnancy, lactation, liver failure, infectious diseases (including herpes shingles, chickenpox, herpes), arrhythmias, myocardial infarction (history), myocardial ischemia, inhibition of bone marrow hematopoiesis after chemotherapy or radiotherapy.

Side effects:
From the side of hematopoiesis and hemostasis system: inhibition of bone marrow hematopoiesis (neutropenia, thrombocytopenia, anemia). The nervous system: ataxia, seizures, encephalopathy, peripheral neuropathy, paresthesia. On the part of the SSA: lowering blood pressure, rarely - increased BP, bradycardia, and or tachycardia, AV block, ventricular bigeminy, mesenteric thrombosis. On the part of the digestive system: nausea, vomiting, diarrhea, decreased appetite, constipation, obstruction and intestinal perforation, ischemic colitis. On the part of the skin and subcutaneous fat: peripheral edema , alopecia (reversible), not heavy defeat of the skin and nails. From a musculoskeletal: arthralgia, myalgia. On the part of the sense organs: reduced visual acuity. Allergic reactions: skin rash, "tides" of blood to the skin of the face and upper chest cells, angioedema, bronchospasm, generalized urticaria. Other: reduced tolerance to infections (any etiology). Laboratory indicators: increase in activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia. Local reaction: flushing, tromboflebit.Peredozirovka. Symptoms: aplasia of the bone marrow, peripheral neuropathy, mucositis. Treatment: symptomatic.

Dosage and administration:
V / a drip for 3 hours 1 time in 3 weeks. Solution before injection diluted to a concentration of 0.3-1.2 mg / ml 0.9% NaCl solution or 5% dextrose. When ovarian cancer - 135-175 mg / sq.m. When breast cancer, non small cell lung lung cancer - 175 mg / m (subject to prolonged infusion of up to 24 h at a dose of 135 mg / m² every 3 weeks). In KS - 135 mg / m or 100 mg / sqm for 3 h, 1 every 2 weeks. Repeated course should be conducted when the number of neutrophils in peripheral blood of more than 1.5 thousand / microliter and platelets - more than 100 thousand / ml. Patients with profound neutropenia (less than 500 cells / mm) or significant peripheral neuropathy, which was developed during the treatment, with repeated treatments should be reduce the dose by 20%. To prevent the development of pronounced allergic reactions in all patients before the introduction of - 20 mg dexamethasone by mouth or IM - for 6-12 h, 50 mg diphenhydramine in / in and 300 mg of cimetidine / v - 30 - 60 min.

Cautions:
During treatment, you should regularly monitor the pattern of peripheral blood, blood pressure, heart rate and the number of breaths (especially during the first hour of infusion), ECG monitoring (and before treatment). In cases of violations of AV conduction after repeated administration is necessary to conduct continuous cardiac monitoring. Has embryo-and fetotoxicity. During treatment, you must use a reliable contraceptive measures. Paclitaxel should be administered under the supervision of a physician hospital or clinic that has experience with anticancer drugs, and if the conditions necessary for coping with complications. In order to introduce is not recommended infusion of polyvinyl chloride. Solutions should be prepared and stored in glass, polypropylene or polyolefin systems and enter through the infusion system with the inner surface of polyethylene, and connects to the system through a membrane filter with pore size of less than 0.22 microns. During the period of treatment must be careful when driving and lesson other potentially hazardous activities that require high concentration and speed of psychomotor reactions.

Interaction:
Cisplatin decreases the total clearance of paclitaxel by 20% (with more pronounced myelosuppression observed when paclitaxel is introduced after cisplatin). Inhibitors of microsomal oxidation (including ketoconazole, cimetidine, verapamil, diazepam, quinidine, cyclosporine, etc.) inhibit metabolism of paclitaxel.