Karboplatin-Ebev

Karboplatin-Ebev – drug with antineoplastic action.

Form of release and structure

Karboplatin-Ebev release in the form of a concentrate for preparation of solution for infusions: transparent, colourless or almost colourless (in brown glass bottles on 5, 15, 45, 60 or 100 ml, on 1 bottle in a cardboard pack).

For preparation of solution for infusions is a part of 1 ml of a concentrate:

• Active agent: карбоплатин – 10 mg;
• Auxiliary components: sodium hydroxide, anhydrous dihydrosodium phosphate, water for injections.

Indications to use

• Germinogenny tumors at women and at men;
• Ovarian cancer;
• Cancer of a neck of uterus;
• Lung cancer;
• Bladder Schmincke's tumor;
• Malignant tumors of a neck and head.

Contraindications

• The expressed functional disturbances of kidneys (at clearance of creatinine of ≤15 ml a minute);
• Plentiful bleedings;
• The expressed miyelosupressiya;
• Pregnancy and period of a lactation;
• Hypersensitivity to drug components, and also to other platiniferous connections.

Route of administration and dosage

Karboplatin-Ebev it is possible to apply as monotherapy or along with other antineoplastic drugs. The doctor sets the dosing mode individually. The drug is administered intravenously in the following dose modes:

• 300-400 mg/m ² intravenously kapelno for 15-60 minutes or in the form of 24-hour infusion;
• 100 mg/m ² intravenously kapelno for 15-60 minutes daily within 5 days.

Administration of drug it is necessary to repeat with an interval not less than 4 weeks at indicators of neutrophils not less than 2000 cells/mm ³ blood and thrombocytes not less than 100000 cells/mm ³ blood. To or after drug use administration of liquid and an artificial diuresis is not required.

The therapeutic dose of Karboplatin-Ebev depending on function of kidneys or a condition of marrow can korrigirovatsya as follows:

• Patients with risk factors (for example, after performing myelosuppressive therapy or at the low functional status): the initial dose should be lowered by 20-25%;
• Patients with functional disturbances of kidneys (at clearance of creatinine it is less than 60 ml in a minute): because of the increased risk of development of a heavy miyelosupressiya the dose of drug needs to be lowered (at clearance of creatinine of 41-59 ml a minute – to 250 mg/m ², at clearance of creatinine of 16-40 ml a minute – to 200 mg/m ²);
• Patients with symptoms of heavy or moderate hematologic toxicity (at quantity of thrombocytes and neutrophils less than 50000 and 500/mm ³ respectively): decrease in a dose by 25% (can be required at monotherapy and the combined scheme of treatment);
• Patients are more senior than 65 years: adjustment initial and the subsequent doses can be required.

These recommendations about the mode of dosing belong to an initial course of treatment. Further doses need to be adjusted depending on Karboplatin-Ebev's portability and development of a miyelosupressiya.

The initial dose of drug in mg can be determined by Kalvert's formula which describes dependence of values of speed of glomerular filtering (SGF in ml/min.) and desirable concentration of Karboplatin-Ebev from time (AUC in mg/ml × mines):

General Dose (mg) = AUC x (SGF + 25)

Desirable AUC value:

• 5-7 мг/мл×мин: when performing monotherapy at earlier not treated patients;
• 4-6 мг/мл×мин: when performing monotherapy at earlier treated patients or when performing the combined treatment (with cyclophosphamide) at earlier not treated patients.

Before introduction Karboplatin-Ebev it is necessary to dilute to concentration 0,5 mg/ml of 0,9% with solution of sodium of chloride or 5% dextrose solution.

Weak solution of drug keeps stability for 8 hours at a temperature of 25 °C and 24 watch at its storage in the refrigerator at 4 °C.

Side effects

During Karboplatin-Ebev's use development of the following side effects is possible:

• Bodies of a hemopoiesis: the major toxic factor limiting a dose of a karboplatin is suppression of function of a marrowy hemopoiesis. Miyelosupressiya has dozozavisimy character. As a rule, the lowest level of thrombocytes and granulocytes/leukocytes is reached in 2-3 weeks from the moment of the beginning of use of Karboplatin-Ebev, at the same time thrombocytopenia meets more often. Usually recovery to the level necessary for introduction of the following dose of drug, takes not less than four weeks. At rather large number of patients symptoms of anemia can be also shown (hemoglobin level less than 11 g/dl). Its intensity depends on a total dose of drug. In certain cases performing transfusion therapy, especially at patients can be required, it is long using drug (for example, it is more than 6 cycles). Also there is a probability of development of such clinical complications as: infectious diseases, fever, bleeding, septic shock / sepsis;
• Digestive tract: in the first 6-12 hours after Karboplatin-Ebev's introduction there is a probability of developing of vomiting and/or nausea (from easy to moderated) which can proceed till 24 o'clock and more. The risk of emetic effect can be reduced at use of antiemetics, continuous intravenous infusion of a karboplatin within 24 hours or fractional introduction of the appointed dose within 5 days in a row. In certain cases can also arise: diarrhea, inflammation of a mucous membrane of a mouth, abdominal pains, locks;
• Central and peripheral nervous system: there is a risk of development of the peripheral neuropathies which are shown, mainly, as paresthesias and decrease in deep tendon jerks (most possibly for patients 65 years at the long or previous treatment are more senior Cisplatinum). Emergence of signs of dysfunction of the central nervous system is also possible. Prolonged use of drug can lead to a cumulative neurotoxicity;
• Acoustic organ: ototoxicity (sonitus and deterioration in hearing);
• Organ of sight: there is a risk of temporary deterioration or total loss of sight (loss of ability to see light is possible and to distinguish colors), and also other disturbances of visual function. As a rule, the complete recovery and/or improvement of sight occurs within several weeks after the therapy termination. At patients with functional disturbances of kidneys the cortical blindness can develop;
• Kidneys: development of easy and temporary increase in concentration of urea and creatinine in blood serum is possible. Acute damages of kidneys are observed in rare instances. The risk of emergence of nephrotoxicity against the background of use of a karboplatin (decrease in clearance of creatinine) increases at increase in a dose of drug, and also at patients who underwent treatment by Cisplatinum earlier;
• Liver: perhaps easy and, as a rule, short-term increase in concentration of aspartate aminotransferase, an alkaline phosphatase and bilirubin in blood serum. Considerable abnormal liver functions can arise at the patients receiving high doses of drug with autologichesky transplantation of marrow;
• Electrolytic balance: the hypocalcemia, a hypopotassemia, a hypomagnesiemia and/or a hyponatremia are possible;
• Allergic reactions: fever, erythematic rash, itch, bronchospasm, small tortoiseshell, anaphylactic reactions, arterial hypotension. These reactions can be observed already in a few minutes after administration of drug. In rare instances exfoliative dermatitis can develop;
• Others: an alopecia, taste changes, an adynamy, grippopodobny symptoms (fever, increase in temperature), a gemolitiko-uraemic syndrome, an arthralgia / миалгия, cerebrovascular disturbances, heart failure and allergic reactions directly in a drug injection site.

Special instructions

The doctor having experience of use of cytotoxic drugs has to carry out Karboplatin-Ebev's introduction. During therapy it is necessary to exercise constant control of development of possible toxic effects, especially at use of high doses.

During Karboplatin-Ebev's use men and women need to use reliable ways of contraception.

To use to preparation and administration of solution syringes, needles, infusional systems and catheters with the content of aluminum does not follow as it can react with active agent, leading to loss of its activity or formation of a deposit.

Once a week it is necessary to control uniform elements of peripheral blood and indicators of function of a liver and kidneys (the clearance of creatinine belongs to the most sensitive indicators).

Also it is recommended to perform periodically neurologic inspections, especially at patients 65 years and at the patients undergoing earlier therapy by Cisplatinum are more senior.

As карбоплатин can lead to development of cumulative ototoksichesky effects, to patients prior to the beginning of and during treatment audio is recommended to pass graphic researches. At clinically significant dysfunctions of hearing the termination of therapy or change of a dose of drug can be required.

During therapy it is necessary to observe all usual instructions accepted for use of cytotoxic medicines.

Medicinal interaction

At simultaneous use of Karboplatin-Ebev with some medicines there can be undesirable effects:

• Other myelosuppressive drugs or radiation therapy: increase in risk of development of hematologic toxicity;
• Aminoglycosides and other nephrotoxic drugs: increase in risk of emergence of ototoksichesky and/or nephrotoxic effects.

Terms and storage conditions

To store in protected from light, the place, dry, unavailable to children, at a temperature up to 25 °C.

Period of validity – 3 years.