Vinca alkaloids antitumor agent of the group
violate tubulin polymerization during cell mitosis. Blocks cell mitosis at metaphase G2-M, causing testosterone cypionate vs enanthate cell death in interphase or at the following mitosis. It acts primarily on mitotic microtubules; with high doses also affects axonal microtubules. The effect of helix tubulin caused by vinorelbine, is less pronounced than that of vincristine.
It penetrates into the fabric and retained therein for a long time. To a large extent absorbed by the lungs, where it reaches a concentration 300 times higher than in plasma. High concentrations determined in spleen, liver, kidney, and thymus, moderate – and heart muscles, the minimum – in adipose tissue and bone marrow.
Not found in the central nervous system.
Biotransformiroetsa in the liver under the influence of isoenzyme CYP 3A4 cytochrome P450. All metabolites have been identified and are inactive except deatsetilvinorelbina-4-0, which is the main active metabolite in the blood. Plasmas
have been identified and sulfo glucuronic conjugates.
The average half-life of vinorelbine in the terminal elimination phase is approximately 40 hours (27,7-43,6). Systemic clearance of vinorelbine is high and close to the speed of blood flow in the liver, an average of 0.72 l / h / kg (0,32-1,26 l / h / kg).
Vinorelbine is mainly excreted in the bile in unchanged form and as metabolites . Less than 20% of the dose excreted by the kidneys unchanged.
Indications for use:
- non-small cell lung cancer;
- advanced breast cancer;
- hormone-refractory prostate cancer (in combination with low doses of oral corticosteroids).
- hypersensitivity testosterone cypionate vs enanthate to vinca alkaloids or other ingredients;
- original absolute neutrophil count <1500 cells / ml of blood;
- initial platelet count <100,000 cells / ml of blood;
- infectious diseases in the first day of therapy or deferred over the past 2 weeks;
- severe liver function impairment is not related to the tumoral process;
- the need for continuous oxygen therapy – in patients with a tumor of the lung;
- Pregnancy and breast-feeding;
- Children up to age 18 years (safety and efficacy of vinorelbine in children has not been studied).
The caution should be applied Navelbin drug in patients with coronary heart disease in history, with respiratory failure, inhibition of bone marrow hematopoiesis (including after previous chemotherapy or radiation therapy), constipation or intestinal obstruction phenomena in history, a history of neuropathy.
Application of pregnancy and breastfeeding period of
preparation Navelbin contraindicated during pregnancy due to the embryotoxic action. When pregnancy occurs during treatment the patient should be advised of the existence of a risk to the fetus, such patients must be more closely monitored. Recommended for expert advice on genetics.
The drug Navelbin contraindicated during breast-feeding. Breast-feeding should be discontinued prior to drug treatment Navelbin.
Dosing and Administration The drug is intended solely for intravenous injection. Intrathecal administration can result in death. The drug Navelbin used as a monotherapy or in combination with other anticancer drugs. When choosing the dose and mode of administration in each individual case should be referred to the literature. Dosage and frequency of administration, and duration of therapy with Navelbin determined by the attending physician.
Preparation of the solution for infusion
preparation Navelbin administered intravenously as a 6-10 minute infusion.
The pre-concentrate is diluted in 0.9% chloride or sodium in 5% dextrose solution to 1.0-2.0 mg / ml concentration (an average of 50 ml).
After administration the vein should be flushed by introducing at least an additional 250 mL of 0.9% sodium chloride solution or 5% dextrose solution.
Storage of the prepared solution for infusion
after dilution of the concentrate in 0.9% of chloride and sodium in 5% dextrose solution is a ready solution for infusion should be administered immediately. If the administration of the drug was not carried out immediately, the duration of storage of the solution should not exceed 24 hours at 2 ° C to 8 ° C Medical practice assumes responsibility for compliance with the conditions of storage of the solution prior to administration.
Non-small cell lung cancer and breast cancer
in monotherapy standard dose is 25-30 mg / m 2 body surface area once a week.
In a standard chemotherapy dose is 25-30 mg / m 2 body surface, but decreases the frequency of administration (e.g. , 1 day and 5 days every 3 weeks and 1 day and day 8 every 3 weeks), depending on the protocol of antitumor therapy.
Prostate cancer, hormone resistant to
usual dose is 30 mg / m 2 body surface area on day 1 and day 8 every 3 weeks, in combination with daily administration of small doses of oral corticosteroids (e.g., hydrocortisone 40 mg / day).
For patients with a body surface area of> 2 m 2 single dose Navelbin should not exceed 60 mg.
Correction of dosage regimen with hematologic toxicity
By reducing the absolute neutrophil count <1500 cells / microliter of blood or thrombocytopenia <100,000 cells / ml of blood the next administration of the drug Navelbin postpone for 1 week.
If due to hematological toxicity had to refrain from 3 weekly introductions, application Navelbin drug should stop.
Special groups of patients Patients with hepatic impairment The pharmacokinetics of vinorelbine is not changed in patients with moderate or severe hepatic insufficiency. Nevertheless, as a precaution recommended dose reduction to 20 mg / m 2 body surface area, and careful monitoring of haematological parameters. Patients with renal impairment Renal excretion of vinorelbine is negligible, so do not need to reduce the dose Navelbin patients with renal insufficiency. Elderly patients Pharmacokinetics vinorelbine is not modified in elderly patients. Paediatric use The safety and efficacy of vinorelbine in children have not been studied.
Adverse reactions are more common than in a few cases, are organized by system-organ class and listed in accordance with the classification of the World Health Organization: very often – 1/10 assignments (≥10%); frequent – 1/100 appointments (≥1% but <10%); infrequent – 1/1000 appointments (≥ 0.1% but <1%); rare – 1/10000 appointments (≥0,01% but <0.1%); very rare – less than 1 / 10,000 appointments (<0.01%).
Infections and infestations: very often – bacterial, viral, fungal infections without neutropenia, different locations, often – bacterial, viral, fungal infections are the result of myelosuppression and / or immunosuppression (neutropenic infections) are usually reversible with appropriate treatment; very rarely – Complicated septicemia in some cases leading to death.
From the side of hematopoiesis: very often -mielosupressiya leading to neutropenia (least number testosterone cypionate vs enanthateof neutrophils observed 7-10 days after initiation of therapy, recovery occurs over the next 5-7 days, cumulation gematotoksichnosti not noted), anemia often – thrombocytopenia, febrile neutropenia ; rarely – sepsis, septicemia.
For the skin : very often – alopecia, rarely – skin rash, erythema on the palms and feet.
From the nervous system: very often – a variety of neurological disorders, including the reduction or loss of deep tendon reflexes; weakness in the legs; rarely – paresthesia, hyperesthesia, paresthesia with severe sensory and motor symptoms are usually reversible (these reactions are usually reversible).
Since the cardiovascular system: rarely – hypotension, hypertension, hot flashes or cold extremities, rarely – ischemic heart disease (angina, myocardial infarction), severe hypotension, collapse, and very rarely – tachycardia, palpitations, atrial fibrillation and violations heart rate.
The respiratory system : – infrequently , dyspnea, bronchospasm, rarely interstitial pneumonia (in combination therapy with mitomycin), acute respiratory distress syndrome -.
From the digestive system : very often – stomatitis, nausea, vomiting, constipation, often – diarrhea, rarely – a dynamic intestinal paresis, pancreatitis.
On the part of metabolism : rarely – hyponatremia; very rarely – a syndrome of inappropriate secretion of antidiuretic hormone.
Local reactions : often – erythema, burning pain at the injection site, change in color of the veins, phlebitis, rarely – if extravasation – inflammation of subcutaneous adipose tissue, possibly necrosis of surrounding tissues.
Allergic reactions : seldom – anaphylactic shock and angioedema.
Laboratory findings : very often – transient increase in liver function tests (ALT, AST); increased levels of bilirubin.
Other : often – fatigue, anorexia, myalgia, arthralgia, fever, pain of different localization, including chest pain, pain in the lower jaw and in tumor formation.
The main toxic effect due to an overdose is bone marrow suppression with a risk of subsequent development of severe infection.
The specific antidote is not known.
In case of overdose, the patient should be hospitalized and carefully monitor the function of vital organs. It should be taken appropriate measures, such as blood transfusions, administration of antibiotics, growth factors. Recommended close monitoring of liver function.
Interaction with other medicinal products and other interactions Pharmaceutical interactions:
- Do not use alkaline solutions to dilute the drug Navelbin (perhaps precipitation);
- should not be confused Navelbin drug with other drugs administered intravenously (perhaps precipitation).
Adverse combination: inhibitors isoenzyme CYP 3A4 (eg itraconazole, ketoconazole) increased neurotoxicity vinorelbine due to the increase of vinorelbine concentration in plasma by lowering its metabolism in the liver; inductors isoenzyme CYP 3A4 (eg, rifampicin, phenytoin) reducing the concentration of vinorelbine because of an increase of its metabolism in the liver; inducers and inhibitors of cytochrome P450 : possible changes in the pharmacokinetics of vinorelbine; mitomycin C: strengthening pulmonology toxicity of mitomycin C (risk of bronchospasm, acute respiratory failure, have been observed rare cases of interstitial pneumonia); paclitaxel: increase in neurotoxicity risk; oral anticoagulants: a mandatory systematic monitoring INR (international normalized ratio), as well as careful monitoring of the patient’s general condition as possible mutual aggravation of side effects; phenytoin : may reduce the anticonvulsant action of phenytoin, decrease in efficacy and an increase of vinorelbine toxicity, cyclosporine, tacrolimus: excessive immunosuppression with risk of lymphoproliferation. cisplatin: frequency granulocytopenia using combinations of vinorelbine with cisplatin higher than monotherapy vinorelbine; cytostatics : mutual possible worsening of side effects, primarily – myelosuppression;
- The drug Navelbin not used concurrently with the X-ray, especially the exciting area of the liver.
- Application Navelbin drug on background radiation therapy leads to radiosensitization;
- Use of the drug Navelbin after radiation therapy can lead to the re-emergence of radiation reactions.
- Treatment with Navelbin should be carried out under the supervision of a physician who has experience with anticancer drugs.
- Treatment is carried out under strict hematological control, determining the number of white blood cells, neutrophils, platelets and hemoglobin level prior to each ordinary administration of the drug.
- Before the on / in, make sure that the needle is in the lumen of the vein. If extravasation of infusion should be stopped, the rest of the dose introduced into another vein.
- In case of shortness of breath, cough, or hypoxia of unknown etiology should examine the patient to rule out pulmonary toxicity.
- Avoid accidental contact with the eyes of the drug. If this occurs, the eyes should be immediately and thoroughly rinse with 0.9% sodium chloride solution.
- The drug Navelbin not used concurrently with the X-ray, especially the exciting area of the liver.
- Due to the immunosuppressive effect of the drug and the possibility of severe infections it is not recommended during chemotherapy to carry out vaccination of live (attenuated) vaccines.
Effects on fertility
- Men and women should use reliable methods of contraception during treatment with Navelbin, and within three months after the end of chemotherapy.
- Patients planning testosterone cypionate vs enanthate the birth of children after completion of therapy with Navelbin, genetic counseling is recommended.
- Because of the possibility of irreversible loss of fertility as a result of the treatment of vinorelbine, patients should be given advice on conservation of sperm prior to treatment drug Navelbin.
Effects on ability to drive vehicles
Given the profile of side effects during treatment with Navelbin must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.