Cisplatin
When ATH:
L01XA01
Characteristic.
Crystalline powder from yellow to orange-yellow. Slowly and very slightly soluble in water and isotonic sodium chloride solution.
Pharmacological action.
Antitumor, alkylating, cytostatic, immunosuppressive.
Application.
Ovarian cancer, prostate, bladder and renal pelvis, Breast, uterus and cervix, horionepitelioma uterus, skin cancer, adrenal, light, GI, ENT, malignant neoplasms of the head and neck, sympathicoblastoma, limfogranulematoz, lymphoma, melanoma, soft tissue sarcoma, osteosarcoma, myetastatichyeskii ascites, germ cell tumors.
Contraindications.
Hypersensitivity (incl. to other drugs, containing platinum), severe renal dysfunction, bone marrow hypoplasia.
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, impairment of renal function (urolithiasis disease, gout, and the like.), hyperuricemia, polyneuritis, hearing disorder, suppression of bone marrow function, prior cytotoxic or radiation therapy, advanced age.
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.
The incidence of side effects when administered contains cisplatin doses 50 mg / m2.
From the digestive tract: anorexia, taste disturbance, stomatitis, nausea, vomiting, gastrointestinal bleeding, abnormal liver function, giperʙiliruʙinemija.
From the nervous system and sensory organs: asthenia, convulsions, dizziness, loss of consciousness, giporefleksiя, paresthesia, decrease in proprioceptive, vibratory, taste sensitivity, muscle-spastic syndrome, myelopathy of the spinal column, peripheral neuropathy, symptom Lhermitte, difficulty in walking, cerebrovascular accident, cerebral artery, optic neuritis, syndrome of inappropriate secretion of ADH, papilledema, change the color sensation (particularly in the yellow-blue portion of the spectrum), uneven pigmentation of the retina in the macula, korkovaya blindness, reduction equilibrium, noise in ears, Valium actions (31%).
Cardio-vascular system and blood (hematopoiesis, hemostasis): mielodeprescia (25–30%): leukopenia, thrombocytopenia, anemia; gemoliticheskaya anemia, bleeding and hemorrhage, myocardial infarction, thrombotic microangiopathy, Raynaud's syndrome, edema of the lower extremities, person, heartbeat, tachycardia, gipotenziya, heart failure.
From the respiratory system: cough, stridor.
With the genitourinary system: nephrotoxicity (28–36%), painful, strangury, mikrogematuriâ, hyperuricemia, giperurikozurija, nephropathy, amenorrhea, inhibition of ovarian function, azoospermia.
For the skin: alopecia, rash, erythematous rash; with a / in the introduction - the formation of infiltration (extravasates), tissue damage at the injection site (redness, swelling, necrosis, fibrous, scarring), cellulitis.
Other: pain syndrome (backache, by), the development of infections, hyperthermia, chills, gipomagniemiya, giponatriemiya, hypocalcemia, kaliopenia, gipofosfatemiя, a decrease in creatinine clearance, increase in AST, urea, Uric acid, creatinine, changes in the level of amylase; Allergic, incl. anaphylactoid reactions.
Cooperation.
Pharmaceutically compatible with aluminum salts (the interaction observed precipitation, leads to inefficiencies). Weakens the effectiveness of immunization inactivated vaccines; using vaccines, containing live viruses, enhances viral replication and side effects of vaccination. Strengthens (mutually) renal toxicity of bleomycin, aminoglycosides, cephalosporins and other., as well as the effects of other drugs, providing nephrotoxic, neurotoxic and myelosuppressive effects. It reduces the therapeutic concentration in plasma anticonvulsants. Can disguise Valium actions (tinnitus and dizziness) while the use of antihistamines, loxapine, meklozinom, fenotiazinami, thioxanthenes, etc.. 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. Other myelotoxicity drugs, Radiation therapy may potentiate the neutropenia, thrombocytopenia. Compatible in combination with other anticancer drugs. Mannitol reduces urinary excretion, when combined with diuretic drugs (furosemide et al.) It increases the risk of damage to the renal tubules.
Overdose.
Symptoms: nausea, vomiting, neuritis, severe bone marrow depression, dizziness, renal, hepatic failure, deafness, blurred vision (including retinal detachment), bleeding.
Treatment: hospitalization, monitoring vital functions; simptomaticheskaya therapy; if necessary - transfusion of blood components, the appointment of broad-spectrum antibiotics, introduction of antiemetics: serotonin antagonists - ondansetron, metoclopramide / in high-dose corticosteroids or (cisplatin should be discontinued).
Dosing and Administration.
B /, B / A 1 mg / min during the preliminary and subsequent hydration or within 6-8 hours provided adequate diuresis. Adults and children (different schemes are used different doses): 37-75 Mg / m2 once every 2-3 weeks; 50-120 Mg / m2 once every 3-4 weeks; 15-20 Mg / m2 daily, during 5 days every 3-4 weeks, or 75-100 mg / m2 once with an interval of 3-4 weeks (no less 4 rates); 150 mg / m2 with an interval of 3-4 weeks 1 once a week at 50-60 mg / m2 (3-4 Sun). When lung carcinoma, squamous head and neck cancer - 60-100 mg / m2 once in 3-4 weeks.
Precautions.
Use only under medical supervision, with experience chemotherapy. There must be adequate measures and tools for the diagnosis, treatment of complications, relief of anaphylactic reactions (adrenaline, oxygen, antihistamines, corticosteroids and others.). Prior to and during treatment (at short intervals) necessary to determine the level of hemoglobin, or hematocrit, BUN, Uric acid, creatinine clearance and serum creatinine, counting the number of white blood cells (overall, differential), Platelet, the concentration of potassium, Magnesium, phosphate, Calcium, complete neurological examination, including audiometry. As a result of the cumulative effect of the treatment should be no more 1 3-4 times per week (the recovery of bone marrow function), число тромбоцитов для последующего курса химиотерапии должно быть более 100·109/l, лейкоцитов — 4·109/l, serum creatinine reduced to 1,5 mg / 100 ml or less. Mielodeprescia more pronounced at high doses, leukopenia and thrombocytopenia develop with 18-23 days (interval 7,5 to 45) after the start of therapy, the level of formed elements is reversed through 39 days (interval 13 to 62 day) postdose (in patients with severe bone marrow suppression, treatment should be discontinued until symptoms resolve gematotoksichnosti). Allergic reactions occur within minutes after administration, nausea and vomiting in 1-4 hours after dosing and continued for 24 no (should be the appointment of antiemetics). Ototoxic effect is a decrease in the threshold of hearing at higher frequencies (4000 and 8000 Hz), the most severe and irreversible in children is. The neurotoxic effects may occur after the administration of a single dose, and after long-term treatment (4-7 Months). Signs and symptoms of neuropathy is usually seen during treatment, In rare cases, after 3-8 weeks after the last dose of the platinum, When the first signs of cisplatin treatment should be discontinued. To reduce nephrotoxicity before treatment is recommended for 6-12 hours and during the subsequent 24 h holding hydration therapy (1-2 5% dextrose 1/5 part of the normal saline solution - 0,18% sodium chloride solution, or 2 l 0,9% sodium chloride solution), diuresis (mannitol furosemide), as well as prophylaxis of nephropathy, due to increased production of uric acid (maximum concentration observed 3-5 days after administration) - The appointment of allopurinol (in some cases) or the use of funds, causing urine alkalinization. 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. 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, as well as the intake of alcohol and acetylsalicylic acid, increase the risk of gastrointestinal bleeding. 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). Dissolution, dilution and administration of the preparation is carried out by trained medical staff with the protection (gloves, masks, clothing and other.).
Cautions.
When the reaction is observed positive Coombs. It is necessary to strictly rely daily dosage and course (especially with continuous on / in). It should not be administered by infusion sets, aluminum parts containing. The solution for the on / in the cook, dissolving the contents of the vial, contains 10 mg or 50 mg lyophilized powder, in sterile water for injection volume 10 ml or 50 ml (to a concentration of no greater than 1 mg / ml). In further diluted 0,9% sodium chloride or 0,9% sodium chloride solution, diluted 5% glucose solution 2-3 times (the solution must contain at least 0,3% sodium chloride, providing the stability of the drug in solution). The prepared solution is stable at a temperature 27 ° C for 20 no, solution, remaining in the bottle after the capture of the drug, stable 28 days in a dark place or for 7 days in daylight.
