Karboplatin

General characteristics. Structure:

Active agent: 1 ml of solution contains a karboplatin of 10 mg.

Additional substances: sodium a hydrochloride, monohydrate of citric acid, water for injections.

Main physical and chemical properties: pure sterile colourless solution.

Pharmacological properties:

Pharmacodynamics. Karboplatin is the drug containing platinum of the second generation; its biochemical properties are similar to properties of the alkylating bifunctional connections. Drug represents a cytotoxic complex of platinum which reacts with nucleophilic sites of DNA. As a result of formation of mezhzvenyevy and vnutrizvenyevy stitchings in DNA, and also stitchings of DNA-protein synthesis of DNA, RNA and proteins is broken. Antineoplastic action of a karboplatin is not specific concerning phases of a cellular cycle.

Pharmacokinetics. After introduction of a karboplatin the most part of a dose is quickly brought out of blood and allocated mainly with urine for 6 hours. The rest of drug is removed in the two-phase way, at the same time the elimination half-life of drug averages 2,5 hours. Karboplatin almost does not contact proteins of a blood plasma owing to what a large amount of free drug in blood is available to bystry removal. Extent of removal of drug with urine indicates that it карбоплатин is almost not late in body tissues. The main way of removal - a kidney. Patients with clearance of creatinine have 60 ml/min. and above 65% of the entered dose with urine for 12 hours and 71% of the entered dose - for 24 hours in the form of a karboplatin are excreted. Only 3-5% of the entered platinum are allocated with urine during the period between 24 and 96 hours. Patients with clearance of creatinine have lower than 60 ml/min. the general clearance and renal clearance of a karboplatin decrease in proportion to decrease in clearance of creatinine therefore at a renal failure the elimination half-life of a karboplatin from blood serum increases that leads to increase in a miyelotoksichnost. Therefore, such patients need to reduce a dose of a karboplatin. Karboplatin is brought almost entirely by means of glomerular filtering, and in tubules of kidneys its low concentration is noted that explains insignificant nefrotoksichny effect of drug in comparison with Cisplatinum.

Indications to use:

Karboplatin-KMP is shown for treatment of malignant new growths. It is applied in the form of monotherapy or in a combination with other chemotherapeutic drugs to treatment of widespread ovarian cancer, small-celled and not small-celled cancer of a lung, cancer of a small egg, a bladder, a neck of uterus, an osteosarcoma. Besides, Karboplatin-KMP is used at treatment of tumors of a brain (medulloblastoma) at children.

Route of administration and doses:

Karboplatin-KMP appoint in a dose 400 mg/sq.m of a body surface, in the form of intravenous infusion. Introduction duration - of 15 minutes till 1 o'clock. The following course of therapy is appointed not earlier, than in 4 weeks. Patients with the increased risk of oppression of function of a marrowy hemopoiesis need to reduce a dose. It is possible to appoint low doses of drug in case of use in a combination with other antineoplastic drugs.
Preparation of solution for intravenous administration. Just before use each bottle of drug Karboplatin-KMP 5% with solution of glucose or 0,9% sodium chloride solution for infusions to concentration of a karboplatin part not higher than 0,5 mg/ml.

Features of use:

Precautionary measures in operating time with drug.
1. Karboplatin-KMP it is necessary to apply under the leadership of the doctor who has experience of use of antineoplastic chemotherapeutic drugs. Therapy has to is carried out only at correctly established diagnosis.
2. At preparation and administration of solution of drug, as well as during the work with other antineoplastic means, it is necessary to adhere to care and to use gloves. In case of drug solution hit on skin or mucous membranes it is necessary to wash away immediately and carefully it from skin water with soap, and mucous to wash out water.
3. Oppression of function of marrow depends on a dose Karboplatina-KMP and can lead to development of an infection and/or heavy bleeding.
4. Karboplatin-KMP can cause vomiting. Its frequency and intensity can be reduced by means of antiemetics.
5. There are data on development of the symptoms similar on anaphylactic which appear the first minutes of administration of drug. In this case adrenergic drugs, corticosteroids and antihistamines are used.
6. Because aluminum can react with Karboplatinom-KMP, leading to formation of a deposit or loss of activity of drug, for preparation and administration of solution Karboplatin-KMP is not recommended to use needles and the other equipment for an intravenous vvvedeniye which contain details from aluminum.
7. There is no sufficient experience of use of drug for children.

Side effects:

From system of a hemopoiesis. The basic limiting a dose with toxicity manifestation Karboplatina-KMP is hemopoiesis oppression. Thrombocytopenia (the quantity of thrombocytes are lower than 50Õ109/l) is observed at 25% of patients, a neutropenia (the quantity of granulocytes are lower than 1Õ109/l) - at 16% of patients, the leukopenia (the quantity of leukocytes are lower than 2Õ109/l) is observed at 15% of patients. The maximum decrease in indicators is usually noted for the 21st day at monochemotherapy. For the 28th day at 90% of patients the quantity of thrombocytes is recovered and makes 100Õ109/l and above, at 74% of patients the quantity of neutrophils exceeds 2Õ109/l, at 67% of patients the quantity of leukocytes makes more than 4Õ109/l. At patients with a renal failure oppression of a hemopoiesis is more expressed. At patients with high severity of the general state the increased frequency of a leukopenia and thrombocytopenia is also observed. Frequency of developing of anemia increases with increase in the entered dose Karboplatina-KMP. In certain cases hemotransfusion can be necessary for patients who receive therapy Karboplatinom-KMP. Oppression of function of marrow can be more expressed when using Karboplatina-KMP in a combination with other drugs which are toxically influencing marrow or together with radiation therapy.
From the alimentary system and a liver. Vomiting arises approximately at 65% of patients, at the same time at one third of these patients it is sharply expressed. Nausea without vomiting occurs in addition at 10-15% of patients. Nausea and vomiting usually stop in 24 hours from an initiation of treatment, symptoms can be controlled antiemetics. Vomiting is more often observed at administration of drug in a combination with other emetogenny means.
Other often noted gastrointestinal phenomena: an abdominal pain (at 17% of patients), diarrhea (at 6% of patients) and a lock (at 6%).
Rejection of functional tests of a liver from norm (for example, ALT, the general bilirubin and an alkaline phosphatase) can be observed at patients with normal initial indicators. These disturbances are, as a rule, not expressed and reversible approximately in half of cases though existence of a metastatic tumor in a liver can complicate the correct assessment.
From TsNS, peripheral nervous system and sense bodys. It is observed at a small amount of patients who were treated Karboplatinom-KMP, and usually characterized by peripheral neyropatiya. Weak paresthesias were more often observed. The risk of development of peripheral neuropathy increases at patients the senior 65 years. Though the general frequency of the peripheral neurologic by-effects connected with Karboplatinom-KMP is low, long therapy by drug can
to lead to a cumulative neurotoxicity. Clinical manifestations of ototoxicity and other touch frustration, such as a vision disorder and changes of taste, meet seldom. There are cases of development of symptoms from TsNS at a small amount of patients. It is considered that these symptoms are most often connected using antiemetics. The vision disorder can be observed at use Karboplatina-KMP in the raised doses. As a rule, sight is recovered completely or considerably for several weeks after the termination of use of high doses.
From kidneys. Development of disturbances from functional tests of kidneys is not the widespread phenomenon at therapy Karboplatinom-KMP. Level of clearance of creatinine - the most informative indicator of function of kidneys at patients who receive Karboplatin-KMP and is the most effective test for correlation of clearance of drug and oppression of function of marrow.
From electrolytic balance. At some patients abnormally low indicators of electrolytes in blood serum can be observed. These disturbances are seldom shown by clinical symptoms and usually do not demand additional administration of electrolytes at therapy Karboplatinom-KMP.
From reproductive system. The azoospermism and an amenorrhea are possible.
Allergic reactions. Hypersensitivity to Karboplatinu-KMP develops in some cases and is shown by existence of rashes, an itch, occasionally - a bronchospasm and hypotension.
Others. Pain in an injection site and an adynamy is often observed. Seldom - an alopecia, side effects from respiratory, cardiovascular and urinogenital systems.

Interaction with other medicines:

At simultaneous use with the drugs rendering miyelodepressivny, nephrotoxic, neurotoxic or ototoksichesky action, perhaps mutual strengthening of toxic effects. It is necessary to avoid joint appointment with aminoglikozidny antibiotics.

Contraindications:

· Hypersensitivity or other compounds of platinum.
· Miyelosupresiya.
· Renal failure (glomerular filtration rate <30 ml/min.).
· Hearing disorder.

Overdose:

Karboplatin-KMP is not present a drug antidote. The overdose of the specified drug can lead to development of the expressed miyelosupressiya and/or insufficiency of function of a liver. At emergence of complications performing adequate symptomatic therapy is shown (considering possible toxic manifestations).

Storage conditions:

To store in the place, unavailable to children. To store in the place protected from light at a temperature of 15-25 °C, to avoid freezing. A period of validity – 2 years.

Issue conditions:

According to the recipe

Packaging:

On 15 ml or 45 ml in a bottle.