Tsikloplatin

General characteristics. Structure:

Active agent: карбоплатин - 50 mg or 200 mg

Excipients: citric acid, sodium hydroxide.

Description:

1 bottle (5 ml) contains: карбоплатин 50 mg, solution of ammonia of 10% - to рН 5,5±0,5, water for infection - to 5 ml;
1 bottle (15 ml) contains: карбоплатин 150 mg, solution of ammonia of 10% - to рН 5,5±0,5, water for infection - to 15 ml;
1 bottle (45 ml) contains: карбоплатин 450 mg, solution of ammonia of 10% - to рН 5,5±0,5, water for infection - to 45 ml

Pharmacological properties:

Pharmacodynamics. CYCLOPLATINUM (карбоплатин) represents the inorganic complex compound containing heavy metal - platinum. Assume that the main mechanism of effect of this drug is caused by linkng with DNA therefore preferential intra spiral stitchings which change structure of DNA are formed and suppress its synthesis. This effect is shown regardless of a phase of a cellular cycle. Gidrotation a karboplatina as a result of which the active form (forms) of drug is formed occurs more slowly, than hydration of Cisplatinum.

Pharmacokinetics. After single introduction of a karboplatin in the form of intravenous infusion lasting one hour concentration in plasma of the general platinum and free (the exposed ultrafiltration) platinum decreases according to two-phase model of kinetics of the first order. The initial stage of half-decay of free platinum makes about 1-2 hours, and terminal half-life is equal to 3-6 hours; the general platinum is characterized by a similar initial stage of half-decay, but terminal half-life at it more long (about 24 hours). At repeated introductions of a dose within four days in a row of accumulation of platinum in plasma it is not noted. In 24 hours after introduction of a dose more than 85% of platinum in plasma are in the state connected with proteins.

Karboplatin is brought preferential by kidneys. About 30% of the entered dose are removed in an invariable look. At patients with clearance of creatinine, equal 60 ml/min. or more, about 65% and 70% of the entered dose are removed respectively within 12 and 24 hours after introduction. As карбоплатин it is removed almost completely by means of glomerular filtering, only very small concentration of a karboplatin is present at renal tubules that, perhaps, explains the small nephrotoxic potential of drug in comparison with Cisplatinum.

Indications to use:

- Ovarian cancer and seminal gland
- Germinogenny tumors at men and women
- Lung cancer
- Bladder cancer
- Cancer of a neck of uterus
- Tumors of the head and neck

Route of administration and doses:

ЦИКЛОПЛАТИН® (CYCLOPLATIN®) it can be applied both in the form of monotherapy, and in combination with other antineoplastic drugs.

To patients with normal function of kidneys the drug is administered in the following dose modes:
• 300-400 mg/sq.m intravenously kapelno within 20-60 minutes or in the form of 24-hour infusion;
• 100 mg/sq.m intravenously kapelno within 20-60 minutes daily within 5 days.

Introduction cycloplatinum not less than 4 weeks at indicators of thrombocytes repeat with an interval not less than 100 000 cells/mm3 of blood and neutrophils not less than 1500 cells/mm3 of blood.

Administration of liquid to or after use cycloplatinum, and also an artificial diuresis is not required.

Depending on a condition of marrow and function of kidneys a therapeutic dose cycloplatinum can korregirovatsya as follows:
• for patients at whom symptoms of moderate or heavy hematologic toxicity are observed (i.e. quantity of thrombocytes and neutrophilic leukocytes less than 50 000 and 500/mm3 respectively) it is necessary to consider the possibility of a dose decline - both in case of monotherapy, and in the combined schemes of treatment - for 25%.
• At patients with symptoms of a renal failure (the clearance of creatinine <60 ml/min.) increases risk of development of toxic effects, in communication with what the dose cycloplatinum should be lowered:

It is necessary to pay attention to number of thrombocytes also: if at glomerular filtering of 30-60 ml/min. the number of thrombocytes makes more than 200 000/ml, then the general dose of a karboplatina - 40 mg, and at the maintenance of thrombocytes less than 100 000-200 000/ml - a dose of a karboplatin has to make 300 mg. At glomerular filtering drug it is not necessary to appoint less than 15 ml/min.

With risk factors (for example, the courses of myelosuppressive therapy conducted earlier, therapy radiation, the general state of disrepair of the patient and/or age more than 65 years) recommends decrease by 20-25% of a dose of drug. At appointment patients cycloplatinum along with nephrotoxic drugs (Cisplatinum) or the drugs possessing a miyelotoksichnost and ototoxicity should resolve an issue of drug dose adjustment also.

Essentially behind function of kidneys, a picture of blood and thrombocytes.

Before a primeneneniye solution cycloplatinum should be subjected to direct vision regarding existence in it of mechanical inclusions and disturbance of coloring. It is necessary to dilute карбоплатин in normal saline solution or 5% glucose solution before achievement of concentration of 1-0,5 mg/ml just before use (no more than in 24 hours after solution preparation).

Features of use:

Introduction cycloplatinum should be carried out under control of the doctor having experience of use of cytotoxic drugs. Constant control behind possible toxic effects at treatment tsikloplatiny is obligatory, especially when using high doses of drug.

It is not necessary to apply to preparation and administration of drug of a needle, the syringes, catheters and infusional systems containing aluminum which can react with karboplatiny, leading to formation of a deposit and loss of activity of drug.

Regularly (weekly) it is necessary to carry out control of uniform elements of peripheral blood and indicators of function of kidneys (the most sensitive indicator - clearance of creatinine).

To periodically perform neurologic inspections, especially at the patients who were earlier carrying out therapy by Cisplatinum and at patients 65 years are aged more senior.

As cycloplatinum can cause cumulative ototoksichesky effects to patients it is necessary to conduct audiographic researches prior to the beginning of and during treatment. In case of clinically significant dysfunction of hearing corresponding change of a dose of drug or the termination of treatment can be required.

Women and men during treatment by Cisplatinum should use reliable ways of contraception.

At use cycloplatinum all usual instructions accepted for use of cytotoxic drugs have to be observed.

In case of hit of drug in eyes it is necessary to wash out immediately their large amount of water or solution of sodium chloride. In case of hit of drug on skin it is necessary to wash out immediately a large amount of water the place of contact with drug. In case of inhalation of drug or its hit in a mouth it is necessary to see a doctor immediately.

Side effects:

From system of a hemopoiesis: the major toxic factor limiting a dose cycloplatinum is suppression of function of a marrowy hemopoiesis. Miyelosupressiya is dozozavisimy. The most tolerable dose - 320-500 mg/sq.m the lowest level of thrombocytes and leukocytes/granulocytes is, as a rule, reached in 2-3 weeks from the beginning of administration of drug. At the same time, thrombocytopenia meets more often. Adequate recovery to the level allowing reception of the following dose, as a rule, takes not less than 4 weeks. At rather large number of patients anemia symptoms (hemoglobin level less than 11 g/dl) which intensity depends on a total dose of drug can be also shown. There can be a need for performing transfusion therapy, especially at the patients undergoing prolonged treatment (more than 6 cycles of administration of drug). There is also a probability of clinical complications, such as fever, infectious diseases, sepsis / septic shock and bleeding.

From kidneys: easy and temporary increase in concentration of creatinine and urea in + blood serum can be observed. Acute damages of kidneys are observed seldom. The risk of emergence of nephrotoxicity against the background of reception cycloplatinum (decrease in clearance of creatinine) increases at increase in a dose cycloplatinum, and also at patients who carried out treatment by Cisplatinum earlier.

Existence of a hyperuricemia is noted approximately in 20% of cases. For prevention or treatment patients need to appoint the drugs interfering loss of urates such as Allopyrinolum.

From digestive tract: in the first 6-12 hours after administration of drug there is a probability of emergence of the nausea and/or vomiting (from easy to moderated) proceeding till 24 o'clock or longer. The risk of emetic effect can be reduced when performing preventive therapy by antiemetics (ондасетрон, гранисетрон, трописетрон), at continuous in/in infusion cycloplatinum within 24 hours or fractional introduction of a dose within 5 days in a row.

In some cases also other types of undesirable impacts on digestive tract, such as inflammation of a mucous membrane of a mouth, diarrhea, locks and abdominal pains can be observed.

From TsNS and peripheral nervous system: there is a probability of emergence of peripheral neyropatiya, generally in the form of paresthesias and decrease in deep tendon jerks that more possibly for patients is more senior than 65 years at the long or previous treatment by Cisplatinum. Perhaps also emergence of symptoms of dysfunction of TsNS. Long therapy by drug can lead to a cumulative neurotoxicity.

From system of hearing: ototoxicity is shown in the form of a sonitus and deterioration in hearing.

From visual system: there is a probability of temporary deterioration or total loss of sight (loss of ability to distinguish colors is possible and to see light), and also other disturbances of visual function. Improvement and/or a complete recovery of sight as prait, happens within several weeks after the termination of administration of drug. At the patients with an impaired renal function undergoing treatment by high doses of a karboplatin the cortical blindness was observed.

From a liver: the lung and, as a rule, temporary increase in concentration of nuclear heating plant, bilirubin and an alkaline phosphatase in blood serum can be noted. At the patients who were on treatment by high doses of a karboplatin with autologichesky transplantation of marrow, considerable abnormal liver functions were observed.

From electrolytic balance: the hypopotassemia, a hypocalcemia, a hyponatremia and/or a hypomagnesiemia are possible. Allergic reactions: erythematic rash, fever, itch, small tortoiseshell, bronchospasm, arterial hypotension, anaphylactic reactions. These reactions can be shown already in a few minutes after introduction cycloplatinum. In rare instances exfoliative dermatitis can be observed.

Other side effects: taste changes, an alopecia, an adynamy, grippopodobny symptoms (temperature increase, fever), a gemolitikouremichesky syndrome, миалгия / an arthralgia, heart failure, cerebrovascular disturbances and allergic reactions directly in a drug injection site.

Interaction with other medicines:

Use of a karboplatin in a combination with other myelosuppressive drugs or radiation therapy can increase risk of emergence of hematologic toxicity.

Use of a karboplatin in a combination with aminoglycosides, and also with other nefrotoksichnesky drugs increases risk of emergence of nephrotoxic and/or ototoksichesky effects.

At use of a karboplatin in a combination with the vaccines containing live viruses replication of a virus of a vaccine can be observed that can lead to decrease in an immune response.

Contraindications:

- Hypersensitivity to a karboplatin or other platiniferous connections;
- The expressed renal failures (the clearance is lower than 15 ml/min.);
- Heavy miyelosupressiya;
- Plentiful bleedings;
- Pregnancy and period of a lactation.

Overdose:

The special antidotes applied in case of overdose of a karboplatin do not exist. At overdose it is necessary to expect more expressed above-mentioned side effects. Symptomatic treatment. In the first 3 hours after administration of drug use of a hemodialysis is possible. Transplantation of marrow and a transfusion of blood can be also effective in case of side effects at disturbances from blood.

Storage conditions:

To store in the place protected from light at a temperature of 5-25 °C. To store in the places unavailable to children! A period of validity the Concentrate for preparation of infusion solution 24 months.
Infusion solution is prepared just before its introduction and stored in the place protected from light no more than 24 hours.

Issue conditions:

According to the recipe

Packaging:

• The solution in bottles containing 50 mg / 5 ml
• The solution in bottles containing 150 mg / 15 ml
• The solution in bottles containing 450 mg / 45 ml