Index of drugs

Advanced ovarian cancer (including second-line treatment in patients who previously received treatment regimens containing cisplatin). Small cell lung cancer.

1 ml of solution contains 10 mg of carboplatin.

An anti-cancer drug, a platinum derivative. Carboplatin, like Cisplatin, induces the production of cross-links between both DNA strands that modify the structure and interfere with DNA synthesis. After intravenous administration, the drug concentration in the blood changes in two phases: the half-life in the initial phase is 90 minutes, in the second phase - about 6 hours. Carboplatin does not bind to plasma proteins to a lesser extent than cisplatin. Initial protein binding is low, in the first 4 hours, it binds to 29% of the drug; after 24 h binds 85-89% of the drug. Carboplatin is excreted mainly via the kidneys. The major part of the drug is excreted during the first 6 hours after administration. Within 24 hours 50-70% of the drug is excreted, 32% of the drug is excreted unchanged. In patients with impaired renal function, the dose should be reduced.

Hypersensitivity to carboplatinum, other compounds containing platinum or auxiliaries of the preparation. Severe renal failure before starting therapy. Severe myelosupression. Pregnancy and breastfeeding.

The drug should only be used in specialized cancer departments; drug should be administered under the supervision of an experienced oncologist. Particularly cautiously used in patients with impaired renal function, using nephrotoxic drugs and in patients previously receiving chemotherapy, in the elderly and weakened (increased risk of carboplatin toxicity, especially myelosuppression). If the number of plates decreases below 50,000 / mm³and the number of white blood cells below 2,000 / mm³, a dose reduction of 25% should be considered or the treatment should be discontinued until the parameters return to normal values, usually after 5-6 weeks. In severe cases, supportive care may be needed for transfusions of blood products. In typical cases, courses of carboplatin should be given no more than once a month. In the event of severe haematological toxicity, maintenance treatment, anti-infective agents against infections complicating existing disorders, transfusions of blood products, autologous bone marrow transplantation, transplantation of peripheral stem cells and hematopoietic drugs may be used. Significant hearing impairment during carboplatin therapy may require dose modification or withdrawal of the preparation. The incidence and severity of carboplatin induced vomiting can be reduced by premedication with antiemetics or by administration of carboplatin by continuous intravenous infusion over 24 h or by intravenous administration in divided doses over 5 consecutive days instead of one intravenous infusion. Particularly effective antiemetics are selective inhibitors of type 3 (5-HT 3) serotonin receptors (e.g., ondansetron) and substituted benzamides (e.g. metoclopramide); in patients with severe or recurrent vomiting, combination therapy may be considered. During treatment with carboplatin the possibility of hyponatraemia should be considered, especially in patients with other risk factors, eg concomitant treatment with diuretics.

Carboplatin has embryotoxic and mutagenic effects, therefore it should not be used in pregnant women. Women and men of childbearing potential should use adequate contraception during treatment and up to 6 months after the end of therapy. Breast-feeding should be discontinued during treatment. As a result of treatment with carboplatin, irreversible infertility is likely to occur, which should be informed to patients.

The toxicity requiring dose reduction of carboplatin is myelosuppression, which is usually reversible and does not accumulate when carboplatin is used as monotherapy, with the recommended frequency of administration.Very common: bone marrow suppression (leukopenia, neutropenia and thrombocytopenia), anemia (approximately 26% of patients required blood transfusion), subclinical decrease in hearing acuity in the high frequency range (4000-8000 Hz), nausea, vomiting, pain and abdominal cramps, increase in blood urea nitrogen, decrease in creatinine clearance, increase in uric acid in the blood, alopecia, muscle pain, electrolyte disturbances (hypokalemia, hypocalcaemia, hyponatremia, hypomagnesaemia), increase in liver enzymes (alkaline phosphatase, AST). Common: cardiovascular disorders, bleeding (leading to death <1% of cases), peripheral neuropathy (mainly hyperalgesia), CNS symptoms, other sensory disturbances (eg taste disorders), visual disturbances, ototoxicity (tinnitus, loss of hearing impairment), respiratory disorders, diarrhea, constipation, mucositis, oesophagitis, stomatitis, increased blood creatinine, genitourinary disorders, skin reactions, arthralgia, infections (leading to death <1% of cases), asthenia, pain, allergic reactions (anaphylactoid reactions, bronchospasm, hypotension, drug fever, urticaria, rash, erythema, pruritus), increased bilirubin, liver dysfunction. Uncommon: heart failure (leading to death), stroke (leading to death), temporary loss of vision, embolism (leading to death), fever, chills. Rare: haemolytic uremic syndrome, anorexia nervosa. Very rare: arrhythmias, cortical blindness, acute renal failure, sepsis, secondary malignancy associated with the treatment, reactions at the injection site (redness, swelling and pain), flu-like syndrome, pulmonary fibrosis, chest tightness and shortness of breath ( this possibility should be considered after ruling out lung hypersensitivity). In addition: neutropenic fever, dehydration, hypertension, necrosis associated with extravasation of the drug, a feeling of disintegration.

Intravenously, infusion, lasting 15-60 min. Adults: 400 mg / m² pc. Subsequent treatment courses can be repeated after at least 4 weeks. In patients with risk factors such as previous myelosuppressive therapy and / or radiotherapy, advanced age or significantly reduced efficacy, it is recommended to reduce the basic dose by 20-25%. The haematological parameters should be monitored weekly to determine the time of the greatest sUPRA (marrow) suppression of bone marrow function and modify the dosage if necessary.Dosage in patients with impaired renal function. Optimal dosage should be determined based on frequent checks of hematological parameters and renal function parameters. The recommended dosage in patients with impaired renal function depends on the creatinine clearance value and should be calculated according to the Calvert formula. The initial dose of carboplatin is calculated using the Calvert formula, based on the initial renal function assessment and the target AUC: Dose (mg) = target AUC (mg / ml) x [GFR (ml / min) +25]. Target AUC 5-7 mg / ml min, carboplatin monotherapy, patient not yet treated; target AUC 4-6 mg / ml min, carboplatin monotherapy, patient previously treated; target AUC 4-6 mg / ml min, carboplatin + cyclophosphamide, patient not yet treated. The dose calculated using the Calvert formula is given in mg, not in mg / m². Dosing in patients with obstructed bone marrow function. In order to adjust the dose, it is recommended to determine nadir hematological parameters during treatment with carboplatin. For patients with platelet count and neutrophil count respectively above 100,000 and 2000 / mm³, the carboplatin dose can be increased by 25%. However, doses of more than 125% of the initial dose are not recommended. For patients with platelet counts and neutrophils between 100,000 and 50,000 and between 2,000 and 500 / mm, respectively³ dose adjustment is not necessary. For patients with moderate or severe haematological toxicity (i.e., the number of platelets and neutrophils will decrease below 50,000 and 500 / mm, respectively³) a dose reduction of 25% or discontinuation of treatment should be considered - both in monotherapy and in combination regimens.Application in children. There is not enough data to establish a safe range of doses in children.Combination therapy. Carboplatin is used in combination with other anticancer medicines at a dosage depending on the chosen treatment regimen. Dosage should be modified depending on the treatment regimen and the results of laboratory blood tests.