Index of drugs

Advanced ovarian cancer of epithelial origin: first-line treatment or second-line treatment if treatment with other drugs has failed. Small cell lung cancer.

1 ml concentrate for making sol. for infusion contains 10 mg of carboplatin.

An anti-cancer drug, a platinum derivative. It shows a comparable effect to the effect of Cisplatin in relation to a wide range of cancers, regardless of the place of their implantation. Carboplatin, like Cisplatin, induces changes in the structure of the DNA, which rely on "the effect of shortening DNA". After carboplatin administration there is a linear relationship between dose and total plasma concentration and free, ultra-combined platinum. The AUC of total platinum also shows a linear relationship between dose and concentration when the creatinine clearance is> 60 ml / min. Repeated dosing for 4 consecutive days does not cause platinum accumulation in plasma. After intravenous infusion lasting 1 hour (25-250 mg / m² ) plasma concentration and plasma platinum levels are reduced in two phases according to the first order kinetics. For free platinum T_0,5 in the first phase is about 90 minutes, and in the second phase about 6 hours. Binding of carboplatin to proteins reaches 85-89% within 24 hours of administration, although in the first 4 hours only 29% of the dose occurs in bound form. Carboplatin is mainly excreted in the urine, approximately 32% of the dose is excreted unchanged.

Hypersensitivity to the active substance or other platinum-containing compounds. Breastfeeding period. Severe myelosupression. Bleeding tumors. Pre-existing severe renal impairment (creatinine clearance ≤20 ml / min).

Carboplatin should be administered under the supervision of a qualified doctor experienced in the use of anticancer treatment. Diagnostic and treatment equipment should be easily available during treatment and in the event of possible complications. In patients with abnormal kidney function or concomitantly receiving other potentially nephrotoxic drugs, the occurrence of prolonged and more severe bone marrow toxicity is more likely. Before starting treatment, during and after treatment, the functional parameters of the kidneys should be carefully evaluated. Under normal conditions, the carboplatin treatment regimen should not be repeated more often than every month. Frequent monitoring of peripheral blood counts is recommended during and after treatment, and at weekly intervals from the end of treatment with the preparation. This will monitor toxicity, help determine nadir and improve the value of hematological parameters and help adjust the Next dose. The lowest platelet level is usually observed between the 14th and 21st days after starting treatment. The largest decrease is observed in patients who have received intense myelosuppressive chemotherapy. The lowest level of white blood cells is between 14 and 28 days after starting treatment. If the number of white blood cells drops below 2000 cells / mm³ or the number of platelets will fall below 100,000 plates / mm³ discontinuation of carboplatin therapy should be considered until apparent improvement in hematological parameters, which usually occurs after 5-6 weeks. Transfusion may be necessary, and a dose reduction is recommended if continuation of therapy. To reduce additive effects, combination therapy with carboplatin with other myelosuppressive compounds should be carefully planned for dose and timing of administration. In patients with severe myelosuppression, supportive transfusion therapy may be necessary. It has been reported that premedication with antiemetics is beneficial in reducing the incidence and severity of nausea vomiting after carboplatin. Carboplatin can cause kidney and liver problems. The use of very high doses of carboplatin (> 5 times a single recommended dose of the drug as monotherapy) was the cause of severe liver and / or renal dysfunction.It is not known whether the use of an appropriate patient hydration program could help to avoid these symptoms with regard to renal function. For moderate to severe changes in renal or hepatic function tests, a dose reduction or discontinuation of treatment is required. The incidence and severity of nephrotoxicity may increase in patients who had kidney problems before carboplatin treatment. Renal impairment is more common in patients who have previously had nephrotoxicity due to treatment with cisplatin. Carboplatin is not recommended in combination with aminoglycosides or other nephrotoxic drugs.
In patients previously treated with platinum, the incidence of allergic reactions may be increased. Patients should be carefully monitored for allergic reactions and, if necessary, should receive appropriate supportive treatment with antihistamines, adrenaline and / or glucocorticoids. The patient's neurological status should be evaluated regularly and the quality of hearing should be checked, especially in patients receiving high doses of carboplatin. Neurotoxicity, such as paresthesia, weakening of deep tendon reflexes and ototoxicity, is more common in patients previously treated with other cisplatin and other ototoxic regimens. The carcinogenic potential of carboplatin has not been studied, but it has been reported that compounds with a similar mechanism of action and mutagenicity are carcinogenic. The safety and efficacy of carboplatin in children has not been proven.

Carboplatin should not be used during pregnancy unless there is a clear indication. Embryotoxic and teratogenic effects of carboplatin and mutagenic properties have been demonstrated. If carboplatin is used during pregnancy, the patient should be informed about the potential risk to the fetus. Breast-feeding should be discontinued during treatment with carboplatin. Both men and women should be informed about the potential risk of adverse effects affecting fertility. Women of childbearing potential should be advised to avoid pregnancy during treatment by using effective contraception during therapy and for 6 months after treatment. Women who are pregnant or get pregnant during treatment must be genetic consulted. Carboplatin has genotoxic properties. It is recommended that men treated with carboplatin not plan to have children during treatment and for 6 months after treatment. They should also seek advice on storing the semen collected before treatment, due to the possibility of irreversible infertility due to treatment with carboplatin. Most forms of chemotherapy have been associated with suppression of oogenesis and spermatogenesis, patients taking carboplatin should be informed about it. Although there have been no reports of carboplatin associated with other platinum preparations. It is possible to regain fertility after exposure to the drug, but this can not be guaranteed.

Very common: bone marrow suppression - carboplatin dose limiting toxicity (may be more severe or prolonged in patients with impaired renal function, previously treated intensively, as well as in patients with poor general condition and over 65 years, may also be more severe during treatment combined with other myelosuppressants, in almost 1/3 of patients who receive the maximum dose of carboplatin as monotherapy, thrombocytopenia with the lowest platelet count lower than 50 x 10⁹/ L; the lowest number of platelets (nadir) usually occurs between day 14 and day 21 and returns to normal after 35 days from the start of treatment; approximately 20% of patients have leukopenia, but the return of leukocytes from the day the smallest number of cells occurs (14-28 days) may be slower and usually occurs 42 days after the start of treatment; neutropenia with neutrophil count below 1 x 10⁹/ l was observed in about 1/5 of patients; hemoglobin below 9.5 mg / 100ml was observed in 48% of patients with normal values ​​before starting treatment); impairment of hearing acuity, which consists of loss of hearing of high frequency sounds - 4000-8000 Hz (15% of patients); vomiting (more than half of patients, ca.1/3 of them vomiting were severe), nausea without vomiting (almost 1/4 of patients) - nausea and vomiting usually occur with a delay up to 6-12 h after carboplatin administration and usually disappear within 24 h after completion of treatment; 1/4 of patients have no nausea or vomiting; vomiting that could not be controlled with antiemetics was observed in only 1% of patients; vomiting appears to occur more frequently in previously treated patients, especially cisplatin; gastrointestinal disorders causing pain (17% of patients); renal toxicity (it is not usually a dose-limiting factor and does not require preventive measures, such as high volume fluid irrigation or forced diuresis, increased uric acid and blood urea nitrogen or serum creatinine); reduction in serum electrolytes (sodium, Magnesium, potassium and calcium) (electrolyte disturbances were not reported to be severe and resulted in subjective and objective clinical signs); hyperuricemia (in about 1/4 of patients, the level of uric acid in the blood can be reduced by using allopurinol); weakness; abnormal liver function tests (usually mild or moderate, in almost 1/3 of patients with normal baseline values, alkaline phosphatase activity is more frequently elevated than AST, ALT and total bilirubin, the majority of these abnormalities recede spontaneously during the course of treatment). Common: hemorrhagic complications (usually small); peripheral neuropathies (6% after discontinuation of therapy; in the majority of patients, neurotoxicity is limited to paresthesia and weakening of tendon reflexes, the incidence and severity are increased in elderly patients and in patients previously treated with cisplatin); clinical ototoxicity (in 1% of patients, tinnitus, hearing loss may persist or worsen in patients with previous cisplatin-treated hearing disorder associated with this treatment, clinically significant loss of hearing occurred in children receiving carboplatin in doses greater than those recommended and combination with other ototoxic agents); diarrhea (6%), constipation (4%), mucositis; Renal impairment (decrease in creatinine clearance less than 60 ml / min, incidence and severity of nephrotoxicity may increase in patients with renal impairment prior to initiation of treatment, renal dysfunction is more likely in patients who have experienced pre-renal nephrotoxicity as a result of cisplatin treatment ); alopecia; malaise, urticaria, flu-like symptoms, erythematous rash, pruritus; allergic reactions (less than 2%) eg skin rash, urticaria, erythematous rash and fever without apparent cause or pruritus. Uncommon: infectious complications; symptoms from o.u.n. (they are often attributed to the use of antiemetics at the same time); secondary tumors (including promyelocytic leukemia, which occurred 6 years after carboplatin monotherapy and preceding irradiation - no causal relationship established); fever and chills without symptoms of infection, reactions at the injection site (pain, erythema, edema, urticaria and necrosis). Rare: neutropenia with fever; isolated cases of life-threatening infections and bleeds; transient visual disturbances (sometimes manifested by transient loss of vision, usually associated with high doses of the drug in patients with impaired renal function, optic neuritis reported on the market); taste disorders, anorexia; hyponatremia; haemolytic-uremic syndrome; anaphylaxis, anaphylactic shock, angioneurotic edema and anaphylactoid reactions (including bronchospasm, urticaria, swelling and sudden redness of the face, dyspnea, hypotension, dizziness, wheezing and tachycardia); severe hepatic dysfunction after administration of carboplatin at doses greater than those recommended (including acute hepatic necrosis). Very rare: cardiovascular events (heart failure, embolism) as well as cerebrovascular events (cases of cerebrovascular accident), isolated cases of hypertension have been reported in isolated cases; pulmonary fibrosis manifested by chest compressions and shortness of breath.

Intravenously. The recommended dose of carboplatin for previously untreated adult patients with normal renal function, i.e. with a creatinine clearance> 60 ml / min, is 400 mg / m² pc.administered as a single dose in a short intravenous infusion of 15-60 minutes. An alternative method of dose determination may be the use of Calvert's formula: dose (mg) = target AUC (mg / ml x min) x [GFR ml / min + 25]. When using carboplatin as monotherapy in a patient not yet treated, the target AUC is 5-7 mg / ml x min and the previously treated patient 4-6 mg / ml x min; when using carboplatin with cyclophosphamide in a patient not yet treated, the target AUC is 4-6 mg / ml x min. Based on the Calvert formula, the total dose of carboplatin is calculated in mg and not in mg / m² pc. Calverta should not be used in patients who have received extensive initial therapy (the following treatment regimens: mitomycin C, nitrosourea, combination therapy with doxorubicin, cyclophosphamide and cisplatin, combination therapy with 5 or more drugs, radiotherapy> 4500 radios, focused on field 20 x 20 cm or more than one box). Treatment with carboplatin should be discontinued for non-responders, disease progression and / or adverse reactions. Treatment should not be repeated earlier than 4 weeks after the previous carboplatin treatment course and / or before the neutrophil count is at least 2000 cells / mm³and the platelet count is at least 100,000 cells / mm³. It is recommended to reduce the initial dose by 20-25% in patients with risk factors such as previous myelosuppressive therapy and poor patient performance status (score 2-4 according to the ECOG-Zubrod scale or below 80 according to the Karnofsky scale). It is recommended to determine the lowest blood counts (nadir) by performing weekly determinations during the initial course of treatment with carboplatin in order to adjust the dosage in the future. Patients with a creatinine clearance below 60 ml / min have an increased risk of bone marrow suppression. To obtain optimal results with carboplatin in patients with impaired renal function, appropriate dosage adjustments and frequent monitoring of both the lowest blood counts (nadir) and renal function are necessary. If the glomerular filtration rate is <20 ml / min, carboplatin should not be administered. In elderly patients, it may be necessary to adjust the dosage at the beginning of treatment or later depending on the physical condition of the patient. The optimal use of carboplatin in combination with other myelosuppressive agents requires dosage adjustments depending on the chosen principles and treatment regimen.
Before infusion, the preparation should be diluted with 5% Glucose or 0.9% sodium chloride solution until a concentration of 0.5 mg / ml is obtained. During the preparation and administration of carboplatin, it is not allowed to use equipment containing aluminum components.