Melfalane
When ATH:
L01AA03
Characteristic.
Derivative of nitrogen mustard, It refers to bifunctional alkylating action tsiklonespetsifichnogo. Powder, almost insoluble.
Pharmacological action.
Antitumor, alkylating, cytostatic, immunosuppressive.
Application.
Multiple myeloma, ovarian cancer, Breast, eggs (especially in the presence of metastases), limfogranulematoz, lymph- and reticulosarcoma, gemangioэndotelioma, Bone reticulosarcoma, sympathicoblastoma, soft tissue sarcoma, erythremia, Ewing's tumor, limfoépitelialʹnaâ opuholʹ Lipstick, cholangiocellular liver cancer, metastatic and localized form of malignant melanoma (a regional administration).
Contraindications.
Hypersensitivity, suppression of bone marrow function (снижение числа лейкоцитов ниже 2·109/л и тромбоцитов ниже 50·109/l), impairment of renal function.
Restrictions apply.
Assessment of the risk-benefit ratio is needed in the appointment of the following cases: enable vetryanaya, herpes zoster and other systemic infections, gout, urolithiasis disease, hyperuricemia, podagricheskiy arthritis, bone marrow infiltration of tumor cells, prior cytotoxic or radiation therapy (It should be given no sooner than 3-4 weeks), children and old age (safety and efficacy have not been studied).
Pregnancy and breast-feeding.
Contraindicated in pregnancy.
Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)
At the time of treatment should stop breastfeeding.
Side effects.
From the digestive tract: anorexia, gastrointestinal bleeding, stomatitis, nausea, vomiting, esophagitis, diarrhea.
Cardio-vascular system and blood (hematopoiesis, hemostasis):
mielodeprescia (leukopenia, thrombocytopenia, anemia), gemoliticheskaya anemia, bleeding and hemorrhage, vasculitis, venookklyuzionnye defeat, cardiac arrest.
From the respiratory system: cough, bronchospasm, Fibrosis of lung tissue, interstitial pneumonia.
With the genitourinary system: painful, strangury, hematuria, hyperuricemia, nephropathy, swelling, proteinuria, amenorrhea, azoospermia.
Allergic reactions: anaphylaxis (2%), anaphylactic shock, angioedema, hives, skin rash, itch.
Other: CNS dysfunction, pain syndrome (backache, by), the development of infections, fever, chills, alopecia, increasing the concentration of 5-HIAA, necrosis of perivascular spaces, sensation of heat and / or stinging at the injection site.
Cooperation.
Weakens the effectiveness of immunization inactivated vaccines; using vaccines, containing live viruses, enhances viral replication and side effects of vaccination. Aminazin, levomicetin, pyrazolone derivatives, radiotherapy and other drugs potentiate the myelotoxicity mielodepressiu (neutropenia, thrombocytopenia). Cyclosporine in the background I / O administration of melphalan may cause severe renal insufficiency, nalidixic acid is hemorrhagic Necrotizing Enterocolitis (children). Cisplatin induced renal dysfunction. The effect amplifies prednisolone. By increasing the concentration of uric acid, reduces the effect of drugs protivopodagricakih (allopurinola, colchicine, probenecid or sulfinpirazona) in the treatment of hyperuricemia and gout (last dose adjustment is necessary). Uricosuric agents increase the risk of nephropathy. There is a cross-hypersensitivity to chlorambucil. Incompatible with the infusion solutions, dextrose; possible joint use with 0,9% (in the weight ratio) sodium chloride solution for infusion.
Overdose.
Symptoms: mielosuprescia, nausea and vomiting, disturbance of consciousness, convulsions, muscle paralysis, nicotinic effects, mukozit, stomatitis, colitis, diarrhea, hemorrhagic shock syndrome, giponatriemiya, nephrotoxicity, respiratory distress syndrome, adult.
Treatment: hospitalization, monitoring vital functions; simptomaticheskaya therapy; if necessary - transfusion of blood components (when pancytopenia), platelet and leukocyte mass, possible bone marrow transplant, the appointment of broad-spectrum antibiotics. Hemodialysis nyeeffyektivyen.
Dosing and Administration.
Inside (before meals), I / (for 15-20 minutes), B / A, gipertermicheskaya regionalynaya perfusion. Dose picked individually, corrected based on the clinical effect and, depending on the severity of haematological Actions. Adults, in multiple myeloma: inside (before meals) - 0,15 mg / kg / day for 4 days, again, at intervals of 6 Sun; in/in-8-30 mg/m2 at intervals of 2-6 weeks (when combined with cytostatics), or 16 mg / m2 (0,4 mg / kg) 1 once every 4 week monotherapy, or once only 100-200 mg/m2 (2,5-5 mg/kg). When ovarian cancer inside — 0,2 mg / kg / day for 5 days, with repeated administration every 4-8 weeks; in/in with monotherapies- 1 mg / kg (40 mg / m2) at intervals of 4 Sun. In combination with zitostatikami-0.3-0.4 mg/kg (12-16 mg/m2) at intervals of 4-6 weeks. Mammary cancer: 0,15 mg / kg or 6 mg / m2 during 5 every day 6 Sun. When eritremii 6-10 mg/day for 5-7 days (induction of remission), further 2-4 mg/day, supporting dose is 2-6 mg per week. Progressive neuroblastoma children — 100-240 mg/m2 during 3 days. Malignant melanoma, and soft tissue sarcoma - Gipertermicheskaya regionalynaya perfusion. If the kidney function (CL 30-50 mL/min) the dose should be reduced by 50%. Полная доза может применяться только при уровне лейкоцитов не ниже 4·109/л и тромбоцитов не ниже 100·109/l; при снижении до 3·109/л и 75·109/l respectively, the dose is 75%, до 2·109/л и 50·109/- 50%. Снижение числа лейкоцитов ниже 2·109/л и тромбоцитов ниже 50·109/l treatment should be discontinued.
Precautions.
Use only under medical supervision, with experience chemotherapy. Prior to and during treatment (at short intervals) you must determine the level of hemoglobin, or hematocrit, the number of leukocytes (overall, differential), Platelet, Uric acid, BUN, creatinine, weight control patients. If the following symptoms: chills, fever, cough or hoarseness, pain in the lower back or side, painful or difficult urination, bleeding or hemorrhage, black stools, blood in the urine or feces - consult your physician immediately. Myelosuppression observed within 2-3 weeks after initiation of treatment (some patients for 5 days), maximum low level within 3-5 weeks, normalizes blood formed elements for 4-8 weeks (the development of severe symptoms gematotoksichnosti treatment should be discontinued until symptoms resolve). Leukemization probability increases with the duration of treatment, and the magnitude of the cumulative dose. In order to eliminate gematotoksichnosti during chemotherapy may be used reinfusion of autologous cryopreserved bone marrow immediately after high-dose therapy, or stimulants hematopoiesis (filgrastim and others.). In the event of thrombocytopenia advised extreme caution when performing invasive procedures, Regular inspection of places on / in the, skin and mucous membranes (for signs of bleeding), limit frequency troublesome and the rejection of the / m injection, control of blood in the urine, vomit, Kale. The patients must be carefully shave, manicure, brush your teeth, dentists use threads and toothpicks, to conduct dental procedures, should be the prevention of constipation, avoid falls and other injuries, drinking alcohol and acetylsalicylic acid, increase the risk of gastrointestinal bleeding. In order to prevent nephropathy, due to increased production of uric acid (most often it occurs in the initial period of treatment), must be sufficient liquid intake, the subsequent increased diuresis, use of allopurinol (in some cases) and the use of funds, causing urine alkalinization. It is important not to take more or less of the drug; if the reception has been missed, dose not filled, and the following is not doubled. Should defer vaccination schedule (carried out not earlier than 3 Months before 1 years after completion of the last cycle of chemotherapy) patient and other family members, residing with him (should abandon immunization oral polio vaccine). Avoid contact with infectious patients, or use non-event for the prevention of (face mask, etc.). During treatment it is necessary to use adequate contraceptive measures. In case of contact with skin or mucous membranes - rinse thoroughly with water (mucosa) or soap and water (skin).
Cautions.
In preparing solutions, melphalan should be guided by the rules of treatment of toxic and irritating to the skin substances. For / in the solution is prepared time: liofilizirovanny powder dissolved in 10 ml of the supplied solvent (should be added soon) and vigorously shake the bottle. The resulting solution was immediately combined with saline (the concentration for the on/in infusion should not exceed 0,45 mg / ml) and immediately begin introduction.
