parabolan online

Parabolan (paclitaxel) is an anticancer drug of natural origin, derived semisynthetic route from the plant Taxus Baccata.
The mechanism of action is associated with the ability to stimulate the “assembly” of microtubules of the dimeric molecules of tubulin and stabilize their structure and inhibit the dynamic reorganization in interphase, which violates the mitotic cell function.
It is dose-dependent suppression of bone marrow hematopoiesis. According to experimental data, mutagenic and embryotoxic properties, causes a decrease in reproductive function.

parabolanFor intravenous (i / v) administration for 3 hours in a dose of 135 mg / m² maximum concentration (Cmax) was 2170 ng / ml, area under “concentration-time” curve (AUC) – 7952 ng / h / ml; when administered in the same dose for 24 hours – 195 ng / mL and 6300 ng / h / ml, respectively. Cmax AUC and dose-dependent: 3 hour infusion at increasing doses up to 175 mg / m results in an increase of these parameters by 68% and 89%, respectively, with 24 hour – 87% and 26%, respectively.
Communication with plasma proteins – 88- 98%. The average volume of distribution – 198-688 l / m². Poluraspredeleniya time of blood in the tissue – 30 min. Easily penetrates and is adsorbed tissue accumulates primarily in the liver, spleen, pancreas, stomach, intestine, heart, the muscles.
It is metabolized in the liver by hydroxylation with cytochrome P450 isoenzymes CYP2D8 (to form a metabolite – 6-alpha gidroksipaklitaksel) and CYP3CA4 (with 3-metabolites form the vapor-gidroksipaklitaksel and 6-alpha, 3-p-digidroksipaklitaksel). Write mainly in the bile – 90%. Repeated infusions are not accumulates.
The half-life and the total clearance is variable and depends on the dose and duration of the on / in: 13.1-52.7 and 12.2-23.8 h l / h / m², respectively. After the on / in 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.


• ovarian cancer (first-line treatment of patients with the common form of the disease or a residual tumor (more than 1 cm) after surgery (in combination with cisplatin) and second-line therapy for metastases after standard therapy has not yielded a positive result).
• Breast cancer ( the presence of the 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 failure of standard therapy – second line therapy).
• Non-small cell lung cancer (therapy first-line patients who had not planned surgery and / or radiation therapy (in combination with cisplatin).
• Kaposi’s sarcoma in AIDS patients (second line therapy).


• Hypersensitivity to paclitaxel or other components of the formulation (including polyoxyethylated castor oil)
• Original content neutrophils less than 1500 / ml in patients with solid tumors.
• Original (or registered in the course of treatment) neutrophils less than 1000 / microliter patients Kaposi’s sarcoma in AIDS patients.
• Pregnancy and lactation.

Precautions : inhibition of bone marrow hematopoiesis (including after chemotherapy or radiation therapy), hepatic failure, acute infectious diseases (including herpes zoster, chickenpox, herpes), severe coronary heart disease, myocardial infarction (in history ), arrhythmias.
The safety and efficacy Parabolan drug in children has not been established.

Dosing and Administration

In order to prevent severe hypersensitivity reactions, all patients must be carried out with the use of premedication glkzhokortikosteroidov, antihistamines and H2 histamine receptor antagonists. For example, 20 mg dexamethasone (or its equivalent) into approximately 12 and 6 hours prior to drug administration Parabolan 50 mg diphenhydramine (or its equivalent) intravenously and cimetidine 300 mg or ranitidine 50 mg intravenously 30-60 minutes prior to drug administration Parabolan.
When you select and dose in each individual case should be guided by the data of literature.
Parabolan administered intravenously as a 3-hour or 24-hour infusion at a dose of 175 mg / m or 135 mg / m with an interval between doses for 3 weeks. The drug is used alone or in combination with cisplatin (ovarian cancer and non-small cell lung cancer), and doxorubicin (breast cancer).
The recommended dose Parabolan preparation for the treatment of Kaposi’s sarcoma in AIDS patients is 100 mg / m 2 as a 3-hour infusion every 2 weeks.
Introduction Parabolan drug need not be repeated for as long as neutrophil not be at least 1500 / ml blood, and platelet count of at least 100,000 / microliter blood. Patients who have after the introduction Parabolana observed severe neutropenia (neutrophil count <500 / ml of blood for 7 days or longer period of time) or severe peripheral neuropathy during subsequent treatments, Parabolana dose should be reduced by 20%.
The solution for infusion prepared immediately prior to administration by diluting a concentrate of 0.9% sodium chloride or 5% dextrose, or 5% dextrose in 0.9% sodium chloride solution for injection or 5% dextrose in Ringer’s solution to a final concentration of 0 3 to 1.2 mg / ml. Opalescent solutions may be prepared for the composition present in the dosage form of the carrier bases, and after filtration the solution opalescence persists parabolan.

In the preparation, storage and administration of drug Parabolan equipment should be used which does not contain parts of PVC.
Parabolan be administered through the system with a built-membrane filter (pore size less than 0.22 micron).

Side effect

The frequency and severity of side effects are dose-dependent. From the side of hematopoiesis: neutropenia, thrombocytopenia, anemia. Myelosuppression, primarily granulocytic germ was the major toxic effects, the dose limiting. The maximum decrease in neutrophil levels is usually observed on the day of 8-11, the normalization occurs on day 22. On the part of the immune system: in the first hours after administration Parabolana may experience hypersensitivity reactions manifested by bronchospasm, decreased blood pressure, pain in the chest, flushing to-face, skin rash, generalized urticaria, angioedema.Described isolated cases of fever and back pain. Cardio-vascular system: decrease in blood pressure (BP), rarely – increased blood pressure, bradycardia, may be tachycardia, dysrhythmia, atrioventricular block, ventricular bigemini, ECG changes, thrombosis of the veins. The respiratory system: interstitial pneumonia, lung fibrosis, pulmonary embolism, as well as more frequent development of radiation pneumonitis in patients while undergoing radiation therapy. from the nervous system: mainly paresthesia. Rarely – seizures type grand mal, visual disturbances, ataxia, encephalopathy, autonomic neuropathy, manifested paralytic ileus and orthostatic hypotension. From the Musculoskeletal System: arthralgia, myalgia. From the digestive system: nausea, vomiting, diarrhea, mucositis, anorexia, constipation. There are few reports of acute intestinal obstruction, intestinal perforation, mesenteric artery thrombosis, ischemic colitis. Liver function: increased activity of “liver” transaminases (often ACT), alkaline phosphatase, and bilirubin in blood serum. Cases of gepatonekroz and hepatic encephalopathy. Skin and skin appendages: alopecia, rarely violation of pigmentation or discoloration of the nail bed.Very rarely – exudative erythema multiforme, including Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, onycholysis. From the senses: blurred vision, conjunctivitis, increased lacrimation. Local reactions: thrombophlebitis, pain, swelling, erythema, induration and pigmentation of the skin at the injection site; extravasation can cause inflammation and necrosis of the subcutaneous tissue. Other: asthenia and malaise, reduced tolerance to infections (any cause).


Symptoms: bone marrow aplasia, peripheral neuropathy, mucositis.
Treatment: symptomatic. Antidote paclitaxel is not known.

Interaction with other medicinal products and other forms of interaction

Cisplatin reduces total clearance of paclitaxel by 20% (the more severe myelosuppression observed when paclitaxel is administered after cisplatin).
Co-administration with cimetidine, ranitidine, dexamethasone or diphenhydramine does not affect the relationship of paclitaxel to plasma proteins.
The inhibitors of microsomal oxidation ( including ketoconazole, cimetidine, verapamil, diazepam, quinidine, cyclosporin, etc.) inhibit the metabolism of paclitaxel.
The polyoxyethylated castor oil, which is part of paclitaxel can cause extraction DEGP [di- (2-hexyl) phthalate] from plasticized polyvinylchloride ( PVC) containers, where the degree of leaching DEGP increases with increasing solution concentration and with time.

special instructions

Application Parabolana should be administered under the supervision of a physician who has experience with anticancer chemotherapeutic agents.
In case of severe hypersensitivity reactions, infusion Parabolan drug should be discontinued immediately and start a symptomatic treatment, and inject the drug again should not be.
During the treatment should be regularly monitored picture peripheral blood, blood pressure, heart rate and the number of breaths (particularly during the first hour of infusion), ECG monitoring (and prior to treatment).
In cases of violations of atrioventricular conduction, after repeated administration necessary to carry out continuous cardiac monitoring.
Patients during treatment Parabolanom and at least 3 months after completion of therapy should use reliable methods of contraception.
in the period of treatment must be careful when driving lesson potentially dangerous activities which require high concentration and psychomotor speed reactions.
Parabolan is a cytotoxic agent, at work with which you must be careful to use gloves and avoid contact with the skin or mucous membranes, which in these cases should be thoroughly washed with soap and water or (eye) with plenty of water.

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