Carboplatin
When ATH:
L01XA02
Characteristic.
Crystalline powder. Soluble in water until the concentration 14 mg / ml, pH 1% solution 5-7, practically insoluble in ethanol, acetone and dimethylacetamide.
Pharmacological action.
Antitumor, alkylating, cytostatic, immunosuppressive.
Application.
Ovarian Cancer, germ cell tumors in men and women, small cell lung cancer and non-small cell, malignant neoplasms of the head and neck, cancer of the cervix and uterus, Breast, Bladder, soft tissue sarcoma, melanoma.
Contraindications.
Hypersensitivity (incl. to other drugs, containing platinum), severe renal dysfunction, mielosuprescia.
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, hearing, clinical signs of bleeding (incl. from tumor tissue), ascites ili ekssudativnyi pleuritis, suppression of bone marrow function, prior cytotoxic or radiation therapy, elderly (senior 65 years) and children's 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.
From the digestive tract: change in taste, anorexia, nausea, vomiting (65%), abdominal pain (17%), constipation and / or diarrhea (6%), gastrointestinal bleeding, abnormal liver function (severity increases with metastatic), stomatitis, inflammation of the mucous membrane of the mouth.
From the nervous system and sensory organs: peripheral neuropathy (6%), changes in the nervous system (5%), asthenia, convulsions, in 1% - decrease in hearing acuity, of view.
Cardio-vascular system and blood (hematopoiesis, hemostasis): mielodeprescia: Thrombocytopenia below 100 · 109/- 90%, below 50 · 109/- 25%, Leukopenia below 4 · 109/- 67%, below 2 · 109/- 15%, Neutropenia below 2 · 109/- 74%, below 1 · 109/- 16%, anemia (The level of hemoglobin is lower 11 g / dl) - 71%, less than 1% cases - heart failure, embolism, cerebrovascular disorders; bleeding and hemorrhage, gipotenziya.
From the respiratory system: cough, breathlessness, bronchospasm.
With the genitourinary system: impairment of renal function, painful, strangury, hematuria, amenorrhea, azoospermia.
For the skin: alopecia (3%), in 2% cases of allergic reactions (rash, itching and others.).
Metabolism: gipomagniemiya (29%), change in the concentration of sodium (29%), hypocalcemia (22%), kaliopenia (20%), increase in alkaline phosphatase activity (24%), AST levels (15%), urea (14%), creatinine (6%), total bilirubin (5%), a decrease in creatinine clearance.
Other: pain syndrome (backache, by), the development of infections, hyperthermia, chills, anaphylactoid reactions.
Cooperation.
Pharmaceutically compatible with aluminum salts (the interaction observed precipitation, leads to inefficiencies). Strengthens (mutually) nephrotoxicity propranolol, aminoglycosides, as well as the effects of other drugs, providing nephrotoxic, neurotoxic, ototoksicheskoe mielusupressivnoe action. Weakens the effectiveness of immunization inactivated vaccines; using vaccines, containing live viruses, enhances viral replication and side effects of vaccination. There is cross-resistance with cisplatin, increases caused by this drug before the neurotoxic and ototoxic effects (observed in 30% patients). Other myelotoxicity drugs, Radiotherapy enhance bone marrow depression (potentiate the neutropenia, thrombocytopenia).
Overdose.
Symptoms: nausea, vomiting, severe bone marrow depression, gepatotoksichnostь, bleeding.
Treatment: hospitalization, monitoring vital functions; simptomaticheskaya therapy; if necessary - transfusion of blood components, the appointment of broad-spectrum antibiotics.
Dosing and Administration.
B /, Dose picked individually, is corrected on the basis of clinical effect, the severity of the toxic effect. B / in a form of infusions, for 15-60 min, by one of the schemes: 1) 300-400 mg / m2 1 once every 4 Sun; 2) 100 mg / m2 daily for 5 days with repetition rate every 4-5 weeks; 3) 150 mg / m2 1 once a week for 4 Sun, then a break - 6 Sun. The total dose can also be calculated by the formula: Planned AUC X (glomerular filtration rate + 25). If previous treatment of myelosuppressive drugs, in patients with baseline hypofunction of bone marrow hematopoiesis, general condition the dose is reduced by 20-25%.
If the kidney function (Cl creatinine <60 ml / min) The recommended dose of carboplatin is 250 mg / m2 At CL Creatinine 41-59 ml / min and 200 mg / m2 with CL creatinine 16–40 ml/min.
B /, as a continuous infusion (time ranges from 1 to 24 no), Patients with high risk factors (testicular tumors or metastatic breast cancer): 1200-2100 mg / m2 (followed by bone marrow transplantation).
Precautions.
Use only under medical supervision, with experience chemotherapy. There must be adequate measures to diagnose and treat possible complications, incl. relief of anaphylactic reactions (adrenaline, oxygen, antihistamines, corticosteroids and others.). Prior to and during treatment (at short intervals) you must determine the level of hemoglobin, or hematocrit, BUN, bilirubin, creatinine clearance, the number of leukocytes (overall, differential), Platelet, IS aktivnosti, the concentration of potassium, Magnesium, sodium, Calcium, complete neurological examination, including audiometry. As a result of the cumulative effect of the treatment should be no more 1 times a 4 Sun (the recovery of bone marrow function), The number of platelets should be more than 100 · 109/l, leukocytes 2 109/l. Maximum low level of white blood cells and platelets observed 2-3 weeks after administration. Restoring to a level, allowing the introduction of a regular dose of carboplatin, usually, It takes at least 4 Sun.
The need to adjust the dosing regimen in patients over 65 years (on 10% increased risk of developing peripheral neuropathy), in patients with existing renal impairment (depending on creatinine clearance) or when combined with other chemotherapeutic agents.
Nausea and vomiting develop 6-12 hours after the administration of the drug and continue within 24 no (should be the appointment of antiemetics). The development of allergic reactions observed within minutes after administration. Ototoxic effect is a decrease in the threshold of hearing at higher frequencies. 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 - you should immediately consult a doctor. 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.). It should refrain from the use in pediatric practice, because the safety and efficacy of its use in children is not identified. 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.
It should not be administered by infusion sets, aluminum parts containing. The solution for the on / in the cook, diluting the contents of the vial of sterile water for injection, 0,9% solution of sodium chloride or 5% glucose solution (to a concentration of no greater than 0,5 mg / ml). Cooked solutions stable at room temperature for 8 no, in the refrigerator within 24 no; store in a dark place.
