Platidiam (cis diamindihlorplatina) represents the antitumor preparation containing heavy metal platinum.
Platidiam has properties similar to those of the bifunctional alkylating agents, and vnutrityazhevye mezhtyazhevye forming crosslinks in the what is tren thereby destroying its function, leading to cell death; wherein the drug has no cyclic phase and specificity. It possesses immunosuppressive and radio-sensitizing properties.
Intravenous infusions for 6-24 hours in plasma drug concentration increases gradually during infusion, reaching a maximum at the end of administration.
Cisplatin is characterized by extensive distribution in the body fluids and tissues; with the highest concentrations are achieved in the kidney, liver and prostate. Platinum, any release of cisplatin, quickly binds to the proteins of tissues and plasma. After two hours, three hours after infusion of 90% platinum in plasma is bound to proteins in order. Cisplatin has the ability to accumulate in the body and is found in some tissues for a further six months after the last dose of drug. Cisplatin biotransformation is performed by rapid non-enzymatic reaction with the formation of inactive metabolites. Has only a cytotoxic effect of cisplatin is not associated with proteins or a platinum-containing metabolites. Half-life of total platinum is very wide individual variability and ranges from 2-72 hours in healthy people, and 1-240 hours in advanced renal failure. Cisplatin is excreted mainly in the urine. Cisplatin may be derived from the systemic circulation by dialysis, but only during the first 3 hours after drug administration.
Platidiam, usually as part of combination chemotherapy regimens are widely used in the treatment of solid tumors following:
- Germ cell tumors of women and men
- Ovarian cancer and testicular
- Lung cancer
- Head and neck what is tren tumors
- Increased sensitivity to cisplatin or other compounds containing platinum, as well as any component of the composite formulation.
- Impaired renal function (serum creatinine over 115 mmol / liter);
- The marked suppression of bone marrow hematopoiesis;
- Cardiovascular disease;
- Pregnancy and lactation;
- Generalized infection;
- Hearing loss.
acute infectious viral diseases (chicken pox, including recently transferred or recent contact with patients, herpes zoster), fungal or bacterial origin; hyperuricemia (gout including manifests and / or urate nefrourolitiazom) nefrourolitiaz, inhibition of bone marrow hematopoiesis (including on the background of the previous radiotherapy or chemotherapy), polyneuritis.
Dosing and Administration
Platidiam can be used both as monotherapy and in combination with other cytostatic at different doses depending on the regimen. At individual dose selection should be guided by the data of literature.Platidiam administered intravenously as an infusion or indications (intraperitoneal tumor) into the abdominal cavity.
Platidiam in monotherapy or in combination with other chemotherapy drugs usually administered in a dose of 50-100 mg / m² as an intravenous infusion every 3-4 weeks, or 15-20 mg / m² intravenously daily for 5 days every 3-4 weeks.
To stimulate diuresis (100 mL / hr), and to minimize the nephrotoxicity of the drug carried hydration. PLATIDIAM before administration intravenously administered to 2 liters of fluid (0.9% chloride or 5% dextrose solution sodium). After the end of infusion additionally introduced what is tren 400 ml of 0.9% chloride or 5% dextrose solution of sodium chloride. Excessive fluid intake and maintain a diuresis must be observed for 24 hours. If intense hydration to maintain adequate urine output is insufficient, you can enter an osmotic diuretic (eg, mannitol).
Platidiam administered intravenously at a rate of no more than 1 mg / min. Long-term infusion held within 08/06/24 hours provided adequate diuresis before administration and during administration.
Platidiam was diluted in 0.9% sodium chloride solution to a concentration of 1 mg / 1 ml. PLATIDIAM pre lyophilisate can be dissolved in 10-25 ml of water for injection.
Not used for dilution PLATIDIAM dextrose (glucose) solution. Note: Since aluminum reacts with cisplatin and inactivates it, and also causes the formation of sludge, is important in the preparation and administration PLATIDIAM not use needles and other material containing aluminum.
From the urinary system: nephrotoxicity (it is cumulative and is a major toxic factor limiting the dose PLATIDIAM). Defeats of kidneys, which are accompanied by damage to the renal tubules can be identified for the first time in the second week after a dose and is manifested by increased serum creatinine, urea, uric acid in the serum and / or a decrease in creatinine clearance. Renal failure usually is mild or moderate, and is reversible at the usual doses PLATIDIAM. On the part of the digestive system: nausea and vomiting, which usually begin during the first hour of therapy and continued for 24 hours or more, are found in 65% patients. These side effects are partially eliminated by the use of standard antiemetics. Severity of these symptoms can be reduced by dividing the total dose, calculated on the treatment cycle into smaller doses which are administered once a day for five days. Among other frequently observed adverse events associated with the gastrointestinal tract marked abdominal pain, diarrhea and constipation. Occasionally may experience minor and transient increase of ACT and ALT levels in the serum. From the hematopoietic system: often – myelosuppression (in most cases with slightly or moderately expressed, and the application of conventional doses is reversible). The lowest levels of white blood cells and platelets are generally detected after about 2 weeks; their original level is restored in most patients for 4 weeks. Also anemia may occur. On the part of the hearing system: unilateral or bilateral tinnitus, hearing loss or no loss occurs in about 10% of patients, usually this side effect is reversible. It was established that the organ of hearing loss is dose-dependent and cumulative, and this side effect more frequently observed in patients are very young or elderly. There are reports of toxic effects of the drug on the vestibular apparatus. From the central and peripheral nervous system. Peripheral neuropathies occur infrequently. Usually they have a sensory nature (eg, paresthesias of the upper and lower limbs), but may also occur, motor disorders (decreased reflexes, and weakness in the lower limbs). Also they can be marked autonomic neuropathy, convulsions, slurred speech, loss of taste and memory loss. It reported in the literature on the development of Lhermitte syndrome (vertebral column myelopathy and autonomic neuropathy). Treatment should be discontinued at the first appearance of these symptoms. Immune system: sometimes marked allergic reactions manifesting as redness and swelling of the face, wheezing in the lungs, tachycardia and lower blood pressure. These reactions may occur within a few minutes after the administration of cisplatin. In rare cases, there may be urticaria, and maculopapular rash. On the part of the system: in rare cases, there are optic neuritis, papilledema, cortical blindness. Also, there may be color perception change, particularly in the yellow-blue part of the spectrum. The only change in the fundus of the eye may be irregular pigmentation of the retina in the macula. These side effects are usually reversible and disappear after discontinuation of the drug.
Violations of the electrolyte balance: hypomagnesemia, hypocalcemia and hypokalemia.Hypomagnesemia and / or hypocalcemia may manifest clinically enhanced muscle sensitivity or seizures, tremor, karpopedalnym spasm (cramps in the hands and feet) and / or tetany. Possible hyponatremia due to the syndrome of inappropriate antidiuretic hormone production. Other: disorders what is tren of the cardiovascular system (coronary heart disease, congestive heart failure, arrhythmia, orthostatic hypotension, thrombotic microangiopathy, etc.), hyperuricemia, slight alopecia, myalgia, fever platinum and gingival line. If the product enters the skin may develop phlebitis, inflammation of the skin and subcutaneous tissue necrosis. cases of violation of spermatogenesis and azoospermia.