Kemoplat

General characteristics. Structure:

Active ingredient: 500 mkg of a tsiplatin.

Excipients: sodium chloride, Acidum hydrochloricum, water for injections.

Pharmacological properties:

Pharmacodynamics. Cisplatinum (cis-diamindichlorplatinum), represents the antineoplastic drug containing heavy metal platinum. Cisplatinum has the properties similar to properties of the bifunctional alkylating agents forming mezhtyazhevy and vnutrityazhevy stitchings in DNA thereby breaking its functions that leads to death of cells; at the same time drug has no cyclic and phase specificity. Has the immunosuppressive and radio sensibilizing properties.

Pharmacokinetics. After bystry in/in infusions (15 min. are 1 h) emergence of Cisplatinum in a blood plasma and Cmax is defined immediately after introduction. At in/in infusions during 6-24 h concentration of drug increases in plasma gradually during infusions, reaching a maximum by the end of introduction. Cisplatinum is characterized by extensive distribution in biological liquids of an organism and in fabrics; at the same time the highest concentration are reached in kidneys, a liver and in a prostate.

Biotransformation of Cisplatinum is carried out by bystry not fermental transformation with formation of inactive metabolites. Cytotoxic action only Cisplatinum untied with proteins, or its platiniferous metabolites possesses.

After a jet injection or in/in injections lasting from 2 to 7 h in the range of doses from 50 to 100 mg/sq.m of T1/2 of Cisplatinum makes about 30 min. of a blood plasma. After introduction of a dose of 100 mg/m the ratio between Cisplatinum and the general free (ultrafiltered) platinum in a blood plasma makes from 0.5 to 1.1. In 3 h after bolyusny introduction and in 2 h after the end of 3-hour infusion of 90% of the general free platinum in plasma it appears in the state connected with proteins. At repeated courses of therapy there is an accumulation of platinum in body tissues, and platinum is found in some fabrics within 6 months after introduction of the last drug dose. T1/2 of the general platinum carries very wide individual variability and fluctuates within 2-72 h at healthy people, and 1-240 h at the expressed renal failure. In 1 h after administration of drug the most part of Cisplatinum is removed through kidneys in not changed look.

The renal clearance of the free (ultrafiltered) platinum also exceeds clearance of creatinine, is nonlinear and depends on a dose, is not established to the speed of outflow of urine and specific features of canalicular secretion and a reabsorption at the patient of strict correlation between renal clearance of the free (ultrafiltered) platinum or Cisplatinum and clearance of creatinine. At daily administration of drug there is a danger of accumulation of the free (ultrafiltered) platinum in a blood plasma. At other modes of introduction there is no such risk. After administration of drug small concentration of platinum are found in bile and a large intestine, but the way of removal of platinum through a digestive tract is insignificant.

Cisplatinum can be brought out of a system blood-groove by dialysis, but only during the first 3 h after administration of drug.

Indications to use:

Cisplatinum, usually as a part of the combined chemotherapy, is widely applied at treatment of the following solid tumors:

— germinogenny tumors of women and men;

— ovarian cancer and small egg;

— small-celled and not small-celled cancer of a lung;

— planocellular cancer of the head and neck;

— bladder cancer.

Besides, Cisplatinum has antineoplastic activity at the following types of tumors:

— cancer of a neck of uterus;

— osteosarcoma;

— melanoma;

— neuroblastoma;

— gullet cancer.

Route of administration and doses:

Kemoplat can be applied both as monotherapy, and in a combination with other cytostatics in various doses depending on the scheme of therapy. At individual selection of a dose it is necessary to be guided by data of special literature. Kemoplat is entered in/in or at indications (intraperitoneal tumors) into an abdominal cavity.

Kemoplat in monotherapy and in combination with other himiopreparata is usually entered in a dose of 50-100 mg/sq.m in a look into infusions each 3-4 weeks or 15-20 mg/sq.m in/in kapelno daily within 5 days each 3-4 weeks.

Recommendations about preparation and administration of solutions for in/in infusions. For the purpose of stimulation of a diuresis (to 100 ml/h) and for the maximum reduction of nephrotoxic effect of drug carry out hydration. Before introduction of Cisplatinum in/in about 2 l of liquid are kapelno entered. Plentiful consumption of liquid and maintenance of a diuresis need to be observed during 24 h. If intensive hydration for maintenance of an adequate diuresis is insufficient, it is possible to enter osmotic diuretic (for example, a mannitol).

Cisplatinum is entered in/in kapelno with a speed no more than 1 mg/min. Long infusions are carried out during 6-8-24 h on condition of a sufficient diuresis before introduction and during administration of drug.

Cisplatinum is diluted in one of the following infusion solutions: 0.9% chloride sodium solution; 0.9%, 0.45% or 0.3% chloride sodium solution in 5% glucose solution. Weak solutions of drug are stable during 6-8 h at a temperature not above 25 °C in the place protected from light.

Note: since aluminum reacts with Cisplatinum and inactivates it, and also causes formation of a deposit, it is very important at preparation and at introduction of Cisplatinum not to use needles and other equipment containing aluminum.

Features of use:

Use at pregnancy and feeding by a breast. It is contraindicated at pregnancy and in the period of a lactation.

Women of childbearing age are recommended by Cisplatinum to use contraceptives during treatment.

The men receiving therapy by Cisplatinum have to use barrier methods of contraception.

Use at abnormal liver functions. Hepatotoxic action: occasionally slight and tranzitorny increases of the ACT, ALT level and bilirubin in blood serum can be noted.

Use at renal failures. From an urinary system: nephrotoxicity has cumulative character and is the major toxic factor limiting Cisplatinum dose. Damages of kidneys which are followed by damage of renal tubules can come to light for the first time on the 2nd week after introduction of a dose and be shown by increase in level of creatinine, urea, uric acid in blood serum and/or decrease in clearance of creatinine. Renal toxicity, as a rule, happens insignificant or moderately expressed and has reversible character at usual doses of Cisplatinum.

Special instructions. Drug has to be used under control of the doctor having experience of use of antineoplastic drugs.

Patients against the background of treatment with Cisplatinum periodically have to look round the neuropathologist. At explicit symptoms of toxic action on TsNS therapy by Cisplatinum should be stopped.

Before therapy it is necessary to carry out an audiometriya and when symptoms of defeat of an acoustic organ appear or a clinical hearing disorder comes to light, the repeated audiometriya is shown. At clinically significant hearing disorder correction of a dosage or cancellation of therapy can be required.

In the course of treatment by Cisplatinum periodic blood test, determination of content of leukocytes, thrombocytes, hemoglobin, uniform elements of blood, renal and hepatic functional tests, and also level of electrolytes in blood serum is necessary.

Repeatedly it is not necessary to appoint drug until the content of creatinine of blood serum does not decrease to 1.5 mg / 100 ml and less and/or the urea nitrogen of blood will not decrease to 25 mg / 100 ml and less, the maintenance of thrombocytes in blood will not become 100 000/mm3, leukocytes - not less than 4000/mm3.

At development of allergic reactions in the form of a face edema, a bronchospasm, tachycardia and hypotonia it is necessary to apply adrenaline, corticosteroids and антигис gaminny drugs.

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

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

Side effects:

From an urinary system: nephrotoxicity has cumulative character and is the major toxic factor limiting Cisplatinum dose. Damages of kidneys which are followed by damage of renal tubules can come to light for the first time on the 2nd week after introduction of a dose and be shown by increase in level of creatinine, urea, uric acid in blood serum and/or decrease in clearance of creatinine. Renal toxicity, as a rule, happens insignificant or moderately expressed and has reversible character at usual doses of Cisplatinum.

From electrolytic balance: hypomagnesiemia, hypocalcemia, hyponatremia, hypopotassemia and hypophosphatemia. The hypomagnesiemia and/or a hypocalcemia can be shown by clinically raised myesthesia or spasms, a tremor, a carpopedal spasm (spasms in brushes and feet) and/or a tetany. The hyponatremia is usually caused by a syndrome of inadequate products of antidiuretic hormone.

From the alimentary system: nausea and vomiting which usually begin during 1 h therapy and proceed during 24 h and more, occur almost at all patients. These side effects only partially are eliminated at use of standard antiemetic drugs. Weight of these symptoms can be reduced by division of the general dose expected a therapy cycle, smaller doses which are entered by 1 times/days within 5 days.

From other often observed undesirable phenomena from the alimentary system diarrhea and a lock are noted pain in a stomach.

From system of a hemopoiesis: against the background of therapy by Cisplatinum the miyelosupressiya often develops, however in most cases it is expressed slightly or moderately, and at use of usual doses has reversible character. The lowest levels of leukocytes and thrombocytes are, as a rule, observed from the 18th to the 23rd day after introduction; at most of patients these indicators it is recovered by 39th day. Also anemia can be observed.

From an acoustic organ: the unilateral or bilateral sonitus, with a hearing loss or without loss, is noted approximately at 10% of the patients gaining Cisplatinum, usually has this side effect reversible character. It is established that defeat of an acoustic organ has dozozavisimy and cumulative character, and this side effect is more often observed at patients of very young or senile age. There are messages on toxic effect of drug on a vestibular mechanism.

From TsNS and peripheral nervous system: peripheral neuropathies arise infrequently. Usually they have the touch nature (for example, paresthesias of upper and lower extremities), but also there can be motor disturbances (decrease in reflexes and weakness in the lower extremities). Also spasms, the muffled speech, loss of taste and loss of memory can be noted a vegetative peyropatiya. It was reported about development of a symptom of Lermitt, a myelipathy of a rachis and an autonomous neuropathy. Treatment by drug should be stopped at the first emergence of such symptoms.

Hypersensitivity: the allergic reactions which are shown in the form of reddening and a face edema, the whistling rattles in lungs, tachycardia and arterial hypotension are sometimes noted. These reactions can arise within several minutes after the beginning of introduction of Cisplatinum. In rare instances urticaria and spotty and papular skin rash can be observed.

From an organ of sight: the optic neuritis, a papilledema, a cortical blindness are in rare instances noted. Also can be observed change of perception of flowers, especially in a yellow-blue part of a range, irregular pigmentation of a retina in the field of a macula lutea can be the only change of an eyeground. These side effects usually have reversible character and disappear after drug withdrawal.

Hepatotoxic action: occasionally slight and tranzitorny increases of the ACT, ALT level and bilirubin in blood serum can be noted.

Others: disturbances from cardiovascular system (an ischemic heart disease, a myocardial infarction, a stroke, congestive heart failure, arrhythmias, orthostatic hypotension, a trombotichesky mikroangiopatiya, cerebral arteritis), a hyperuricemia, increase in level of amylase in blood serum, an insignificant alopecia, a mialgiya, fever, a hiccups and the gingival line of platinum. At hit of drug under skin development of phlebitis, an inflammation of a hypodermic fatty tissue and necrosis of skin is possible.

Cases of disturbance of a spermatogenesis and azoospermism are noted.

Interaction with other medicines:

Simultaneous or consecutive use of Cisplatinum with antibiotics aminoglycosides (gentamycin, Kanamycinum, streptomycin) or with other potentially nefrotoksichny drugs (for example, Amphotericinum In) can exponentiate its nephrotoxic and ototoksichesky action.

"Loopback" diuretics (furosemide, Clopamidum, Acidum etacrynicum) can increase ototoxicity of Cisplatinum.

It is known that Cisplatinum can break removal through kidneys of Bleomycinum and mechotreksat (perhaps, owing to the nephrotoxic action caused by Cisplatinum) and to increase toxicity of these drugs.

At simultaneous use of Cisplatinum, hexamethylmelamine and a pyridoxine at cancer therapy of ovaries reduction of duration of remission is noted.

At the patients receiving Cisplatinum and anticonvulsant drugs, concentration of the last in blood serum can decrease to subtherapeutic values.

Cisplatinum can cause increase in concentration of uric acid in blood. Therefore patients who at the same time accept medicines for treatment of gout such as Allopyrinolum, colchicine, пробенецид or Sulfinpyrazonum, can have a need of correction of a dosage of these drugs to control a hyperuricemia and attacks of gout.

At interaction of Cisplatinum with aluminum the deposit is formed.

Contraindications:

— a renal failure (creatinine level in serum more than 115 µmol/l);

— oppression of a marrowy hemopoiesis;

— pregnancy;

— lactation period;

— hypersensitivity to Cisplatinum or other connections, containing platinum.

With care - decrease in hearing, a polyneuritis, acute infectious diseases, chicken pox (including recently postponed or recent contact with the patient), shingles, gout in the anamnesis, a nephrolithiasis, beam or chemotherapy in the anamnesis.

Overdose:

Simpotoma: renal failures, a liver, a vision disorder (including retina amotio) and hearing (deafness), the expressed miyelosupressiya, unrestrained nausea and vomiting and/or neuritis. At overdose the lethal outcome is possible.

Treatment: the antidote in case of drug overdose Kemoplat is unknown. The effect, at least partial, is reached only by means of a hemodialysis if it is applied during the first 3 h after overdose as platinum quickly contacts proteins of plasma. Symptomatic therapy is applied to elimination of symptoms of overdose.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

20 ml - bottles of dark glass (1) - a box cardboard.