Platidiamum

General characteristics. Structure:

1 bottle with the lyophilized powder contains:

active agent
Cisplatinum 10, 25 mg or 50 mg and

excipients
Mannitolum, sodium chloride, Acidum hydrochloricum.

Contains active agent in 1 ml of solution - Cisplatinum of 0,5 mg and excipients - sodium chloride, potassium chloride, ammonium chloride, Acidum hydrochloricum, water for injections.

Description

Lyophilisate - yellowish porous weight
Solution for injections - transparent solution with slightly yellowish shade.

Pharmacological properties:

Pharmacodynamics. The antineoplastic means of the alkylating type derivative of platinum. Though the mechanism of its action is definitely not installed, assume that it is similar to the mechanism of action of bifunctional alkylating agents, i.e. vozmodno its linkng with DNA and disturbance of its function that leads to death of cells, at the same time drug has no cyclic and phase specificity. To a lesser extent, suppresses synthesis of protein and RNA.

Platidiamum also has the immunosuppressive and radio sensibilizing properties. The therapeutic effect remains within several days after introduction.

Pharmacokinetics. After bystry intravenous infusion (15 min. - 1 hour) emergence of Cisplatinum in a blood plasma and the peak of its concentration is defined immediately after introduction. At intravenous infusion within 6-24 hours concentration of drug increases in plasma gradually during infusion, reaching a maximum by the end of introduction. Tsisplatina is well distributed in biological liquids of an organism and in fabrics. The highest concentration are reached in kidneys, a liver and a prostate gland. Collects also in skin, a spleen, adrenal glands, a small intestine, a thymus, testicles, a uterus and bones.

Contents in SMZh low though significant amounts can be found in intracerebral tumors.

The platinum released from Cisplatinum, but not actually Cisplatinum, quickly contacts blood proteins (albumine, gamma-globulin, transferrin) for 90% and cellular elements of plasma (including erythrocytes). It is quickly metabolized by non-enzymatic transformation into inactive metabolites. Biotransformation of Cisplatinum is carried out by bystry not fermental transformation with formation of negative metabolites. Cytotoxic effect only Cisplatinum which is not connected with proteins or its platiniferous metabolites has.

The elimination half-life of the general platinum carries very wide individual variability and fluctuates within 2-72 hours at healthy people and 1-240 hours at the expressed renal failure. Cisplatinum is removed generally with urine (70-90%). Cisplatinum can be brought out of a system blood-groove by dialysis, but only within the first 3 hours after administration of drug.

Indications to use:

Platidiamum, usually as a part of schemes 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, cancer of a lung, tumor of the head and neck, cancer of a neck of uterus, bladder, osteosarcoma, melanoma, neuroblastoma, gullet cancer.

Route of administration and doses:

Platidiamum 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. Platidiamum is entered intravenously or at indications (intraperitoneal tumors) into an abdominal cavity. As monotherapy Platidiamum is entered in a dose of 50-120 mg/sq.m in the form of intravenous infusion each 3-4 weeks or 15-20 mg/sq.m intravenously kapelno daily within 5 days each 3-4 weeks.

For the purpose of stimulation of a diuresis and for the maximum reduction of nephrotoxic effect of drug carry out hydration. Before introduction of Platidiamum about 2 liters of liquid are intravenously kapelno entered (0,9% solution of sodium of chloride or 5% Dextrosums/glucose solution). Then intravenously kapelno with a speed 1мг/м2/мин Platidiamum not less than 1 mg/ml diluted in 0,9% chloride sodium solution in concentration is entered. After the end of infusion 400 ml of 0,9% of solution of sodium of chloride or 5% of solution of Dextrosums/glucose are in addition entered. For strengthening of a diuresis within the last 30 minutes of preliminary hydration or after its termination it is possible to enter intravenously kapelno 375 ml of 20% of solution of a mannitol for injections. Plentiful consumption of liquid and maintenance of a diuresis need to be observed within 24 hours.

Long infusions are carried out within 6-8-24 hours, at the same time, Platidiamum dilute in 1-2 liters 0,9% of solution of sodium of chloride for injections.

The lyophilized Platidiamum powder should be dissolved previously in 10-25 ml of water for injections.

Not to use glucose solutions for dilution of Platidiamum.

Note: As aluminum reacts with Cisplatinum and inactivates it, it is very important at preparation and at introduction of Platidiamum not to use needles, syringes, catheters and sets for in/in the introductions containing aluminum.

Features of use:

• Introduction of Platidiamum should be carried out under control of the doctor having experience of use of antineoplastic drugs.
• Men and women of childbearing age during treatment by Platidiamum have to use reliable methods of contraception.
• Patients against the background of treatment with Platidiamum periodically have to look round the neuropathologist. At explicit symptoms of toxic action on TsNS therapy by Platidiamum 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 Platidiamum 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.
• At use of Platidiamum 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 0,9% chloride sodium solution. In case of hit of drug under 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 Platidiamum dose. Damage 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 a klirenm of creatinine. The renal failure, as a rule, happens insignificant or moderately expressed and has reversible character at usual doses of Platidiamum.

From bodies of a hemopoiesis: against the background of therapy by Platidiamum 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, as a rule, come to light approximately in 2 weeks, their initial level at most of patients is recovered within 4 weeks. Also anemia can be observed.

From water and electrolytic balance: hypomagnesiemia, hypocalcemia, hypopotassemia. 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 caused by a syndrome of inadequate products of antidiuretic hormone is possible.

From a GIT: nausea, vomiting which usually begin within the first hour of therapy and proceed within 24 hours and more, occur at 65% of 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 within 5 days once a day. From other often observed undesirable phenomena from a GIT pains in a stomach, diarrhea, a lock are noted.

From TsNS and peripheral nervous system: peripheral neuropathy arises infrequently. Usually they have the touch nature (for example, paresthesias of upper and lower extremities), there can also be motor disturbances (decrease in reflexes, weakness in the lower extremities). Also spasms, the muffled speech, loss of taste, memory can be noted vegetative neuropathy.

From sense bodys: ototoxicity (develops at 10-30% of patients, generally at use of high doses - a sonitus, decrease in hearing up to one - or a bilateral hearing loss within frequencies from 4000 to 8000 Hz).

The optic neuritis, papilledema, cortical blindness is in rare instances noted. These side effects usually have reversible character and disappear after drug withdrawal.

From CCC: Ischemic heart disease, congestive heart failure, arrhythmias, orthostatic hypotension, trombotichesky mikroangiopatiya etc.)

Allergic reactions: a face edema, skin rash (are eliminated in/in introduction of Epinephrinum, GKS and/or antihistamines).

Others: hyperuricemia, insignificant alopecia, mialgiya, fever and gingival line of platinum. At hit of drug under skin development of phlebitis, cellulitis, a skin necrosis is possible. Cases of disturbance of a spermatogenesis and an azospermiya are noted.

Interaction with other medicines:

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

Mannitolum reduces removal of Cisplatinum with urine, increasing thereby ototoxicity of Platidiamum.

Cisplatinum can break removal through kidneys of Bleomycinum and methotrexate (it is possible owing to the nephrotoxic action caused by Cisplatinum) and to increase toxicity of these drugs.

At the patients receiving Cisplatinum and Phenytoinum, concentration of Phenytoinum in serum can decrease. Cisplatinum can vvzyvat increase in concentration of uric acid in blood. Therefore patients who at the same time accept lekarstvenny means for treatment of gout such as Allopyrinolum, colchicine, пробеницид or Sulfinpyrazonum, can have a need to correct dosages of these drugs to control a hyperuricemia and attacks of gout.

Contraindications:

Hypersensitivity to Cisplatinum or other connections containing platinum:
• a renal failure (creatinine level in serum more than 115 µmol/litre);
• miyelodepressiya;
• heart failure;
• pregnancy, lactation period;
• generalized infections.

Precautionary measures

Administration of drug should be carried out under the control of the doctor having experience of use of cytotoxic drugs.

Before the beginning and during treatment it is necessary to control audiogramma indicators. At children the probability of emergence of ototoxicity is higher, than at adults. At clinically significant hearing disorder correction of a dosage or cancellation of therapy can be required.

Before therapy, and then before introduction of the subsequent doses, it is necessary to control function of kidneys (urea and creatinine of blood serum, KK), electrolytes, quantity of erythrocytes, leukocytes and thrombocytes, hemoglobin, uniform elements of blood, function of a liver and the neurologic status.

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

The men receiving therapy by Platidiamum of a dolzhnva to use barrier methods of contraception.

It is necessary to consider the increased risk of development of anaphylactoid reactions in the patients having relatives with allergic diseases.

At use of Platidiamum all instructions accepted for use of cytotoxic drugs have to be observed. Pregnant women should not work with Cisplatinum For reduction of risk of bacterial pollution, cultivation of drug is recommended to be carried out just before use and to begin administration of mix as soon as possible after its preparation. Cultivation is carried out in specially intended zone (preferably in a laminar case for work with cytotoxic substances). During the work with Cisplatinum it is necessary to put on a protective dressing gown, a mask, gloves and to protect eyes. At accidental contact of solution with skin and mucous membranes, the struck area needs to be washed out immediately carefully water with soap.

Overdose:

The acute overdose can cause strengthening of its toxic action in comparison with expected (for example, a renal failure, a heavy miyelosupressiya, unrestrained nausea and vomiting, heavy toxic action on neurosensory structures, a liver failure etc.) up to a lethal outcome. The antidote with the proved efficiency at overdose of Cisplatinum does not exist.

At emergence of symptoms of overdose it is necessary to carry out a hemodialysis within the first 3 hours as platinum quickly and intensively contacts proteins of plasma. The symptomatic treatment is applied to elimination of symptoms of overdose.

Storage conditions:

To store the lyophilized powder for preparation of injection solution in the place protected from light at a temperature not above 25 °C.
To store solution for injections in the place protected from light at a temperature of 10-25 °C.
TO STORE IN THE PLACE, UNAVAILABLE TO CHILDREN

Period of validity

The lyophilized powder for preparation of injection solution - 3 years.
Solution for injections - 2 years.
It is forbidden to use after the period of validity specified on packaging!

Issue conditions:

According to the recipe

Packaging:

The lyophilized powder for preparation of injection solution in bottles:
• on 10 mg No. 1 or No. 10,
• on 25 mg No. 1 or No. 5 and
• on 50 mg No. 1

Bottles invest together with the application instruction in a cardboard pack.

Solution for injections - On 20, 50 and 100 ml of solution for injections are packed into bottles: the bottles containing 10 mg / 20 ml No. 1 or No. 10, 25 of mg / 50 ml No. 1 or No. 5 and 50 of mg / 100 ml No. 1

Bottles invest together with the application instruction in a cardboard pack.