Anticancer agent containing the heavy metal platinum. Cisplatin has properties similar to those of the bifunctional alkylating agents, and vnutrityazhevye mezhtyazhevye forming crosslinks in the DNA thereby destroying its function, leading to cell anavar cycle death; wherein the drug has no cyclic phase and specificity. It possesses immunosuppressive and radiosensitizing properties. After rapid intravenous infusion (15 min – 1 hour) in the emergence of cisplatin and the peak plasma concentration is determined immediately after administration. 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. Cisplatin biotransformation is performed by rapid non-enzymatic reaction with the formation of inactive metabolites. Cytotoxic effect has only cisplatin is not associated with proteins, or a platinum-containing metabolites. After blasting, injection or intravenous infusion duration from 2 to 7 hours in a dosage range of from 50 to 100 mg / m² half-life of cisplatin from plasma is approximately 30 minutes. After administration of 100 mg / m, and the ratio between the total free cisplatin (ultrafiltered) platinum in plasma ranges from 0.5 to 1.1. Three hours after the bolus administration, and two hours after anavar cycle a three-hour infusion of 90% of the total free platinum is protein-bound in plasma state. With repeated courses of therapy occurs platinum accumulation in body tissues, and platinum is found in some tissues for a further six months after the last dose of drug. 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. After 1 hour after administration of cisplatin, most of the drug is excreted through the kidneys in unchanged form. The renal clearance of free (ultrafilter) platinum also exceeds creatinine clearance, is nonlinear and depends on the dose, urine flow rate and the individual characteristics of tubular secretion and reabsorption of the patient. A strict correlation between renal clearance of free (ultrafilter) plugins or cisplatin and creatinine clearance is not established. With daily administration of the drug there is a risk of accumulation of free (ultrafilter) platinum in plasma. For other modes of administration no such risk. After dosing low concentrations of platinum found in the bile and the large intestine, but platinum excretion path through the digestive tract is small. Cisplatin may be derived from anavar cycle the systemic circulation by dialysis, but only during the first 3 hours after drug administration.
- Germ cell tumors of women and men
- Ovarian cancer and testicular
- Small cell and non-small cell lung cancer
- Squamous cell carcinoma of the head and neck
- Bladder cancer
Furthermore, cisplatin has antitumor activity for the following types of tumors:
- Cervical cancer
- Esophageal carcinoma
- Hypersensitivity of cisplatin or other compounds containing platinum;
- Impaired renal function (serum creatinine over 115 mmol / titer);
- Inhibition of bone marrow hematopoiesis;
- Pregnancy and lactation.Be wary – hearing loss, polyneuritis, acute infectious diseases, chicken pox (including recently transferred or recent contact with sick), shingles, gout is a history of nephrolithiasis, radiation or chemotherapy history.
Dosing and Administration
Kemoplat 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.
Kemoplat intravenously or testimony (intraperitoneal tumors) to the abdominal cavity.
Kemoplat in monotherapy and in combination anavar cycle with other chemotherapy is 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.
Guidelines for the preparation and administration of the solution for intravenous infusion
In order to stimulate urine output (up to 100 mL / hr) and to minimize the nephrotoxicity of the drug carried hydration. Prior to administration of cisplatin intravenously administered up to 2 liters of fluid.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).
Cisplatin is 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.
Cisplatin is diluted in one of these infusion solutions: 0.9% sodium chloride solution; 0.9%, 0.45% or 0.3% sodium chloride solution in 5% glucose solution. Diluted solutions of the drug stable for 6-8 hours at a temperature no higher than 25 ° C in a dark place.
Note: Since the aluminum reacts with cisplatin and inactivates it. and also causes the formation of sludge, is important in anavar cycle the preparation and administration of cisplatin does not use needles and other material containing aluminum.
From the urinary system: Renal toxicity is cumulative and is a major toxic factor limiting the dose of cisplatin. 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 toxicity, as a rule, is low to moderate and is reversible at the usual doses of cisplatin. From the electrolyte balance: hypomagnesemia, hypocalcemia, hyponatremia, hypokalemia and hypophosphatemia. Hypomagnesemia and / or hypocalcemia may manifest clinically enhanced muscle sensitivity or seizures, tremor, karpopedalnym spasm (cramps in the hands and feet) and / or tetany. Hyponatremia is usually caused by the syndrome of inappropriate antidiuretic hormone production. On the part of the gastrointestinal tract. Nausea and vomiting, which usually begin during the first hour of therapy and continued for 24 hours or more, are found in almost all 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 from the gastrointestinal tract marked by abdominal pain, diarrhea and constipation. From the hematopoietic system. The therapy with cisplatin often develop myelosuppression, but in most cases it is expressed mild or moderate, and when applying the usual dosage It is reversible. The lowest levels of white blood cells and platelets are generally observed with the 18 th to 23 th day after administration; the majority of patients, these figures restored to the 39th day. Also, there may be anemia. On the part of the hearing system. Unilateral or bilateral tinnitus, hearing loss or no loss occurs in about 10% of patients treated with cisplatin, typically 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 on the development of a symptom Lhermitte, myelopathy of the spinal column, and autonomic neuropathy. Drug treatment should be discontinued at the first appearance of symptoms.Hypersensitivity. Sometimes there allergic reactions manifesting as redness and swelling of the face, wheezing in the lungs, tachycardia and hypotension. 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, nipple swelling of the optic nerve, 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. The toxic effect on the liver. Occasionally may experience minor and transient increase in ACT levels of ALT and serum bilirubin. Other side effects. Violations of the cardiovascular system (coronary heart disease , myocardial infarction, stroke, congestive heart failure, arrhythmia, orthostatic hypotension, thrombotic microangiopathy, cerebral arteritis), hyperuricemia, increased levels of serum amylase, slight alopecia, myalgia, fever, hiccups and gingival platinum line. If the product enters the skin may develop phlebitis, inflammation of the subcutaneous fat and skin necrosis. Cases of violation of spermatogenesis and azoospermia.
Interaction with other medicinal products and other forms of interaction
The simultaneous or sequential application of cisplatin, aminoglycoside antibiotics (gentamicin, kanamycin, streptomycin) or with other potentially nephrotoxic drugs (eg, amphotericin B) may potentiate its nephrotoxic and ototoxic effects.
“Loop” diuretics (furosemide, clopamide, ethacrynic acid) may strengthen ototoxicity of cisplatin.
it is known that cisplatin may interfere with the excretion through the kidneys bleomycin and methotrexate (possibly due to cisplatin-induced nephrotoxicity) and enhance the toxicity of these drugs.
In an application of cisplatin, hexamethylmelamine and pyridoxine in the treatment of ovarian cancer was a decrease in the duration of remission.
patients receiving cisplatin and anticonvulsants last concentration in serum may be reduced up to values ??subtherapeutic.
cisplatin may cause an increased concentration of uric acid in the blood. Therefore, patients who take both drugs for the treatment of gout such as allopurinol, colchicine, probenecid or sulfinpyrazone, correction may be necessary dosage of these drugs, to control attacks of gout and hyperuricemia.
The reaction of cisplatin with aluminum precipitate formed.
The main expected overdose complications are renal dysfunction, liver, visual disturbances (including retinal detachment) and hearing loss (deafness), severe myelosuppression, nausea and uncontrollable vomiting and / or neuritis. In case of overdose may be fatal.
The antidote in case of an overdose of the drug is unknown Kemoplat. The effect, at least partially, is achieved only by dialysis, if it is used for the first three hours of the overdose, as platinum rapidly bound to plasma proteins. To eliminate the symptoms of overdose symptomatic treatment applied.
- The drug should be used under the supervision of a physician who is experienced in the use of anticancer drugs.
- Women of childbearing age is recommended during treatment with cisplatin to use contraceptives.
- Men receiving cisplatin therapy should use barrier methods of contraception.
- Patients on treatment with cisplatin should be inspected periodically neurologist. When obvious symptoms of toxic effects on the CNS cisplatin therapy should be discontinued.
- Before starting therapy should be audiometry, and in cases where there are symptoms of the organ of hearing or hearing impairment are detected clinically, shows repeated audiometry. If clinically significant hearing impairment may require a dosage adjustment or cancellation of therapy.
- In the treatment of cisplatin requires periodic analysis of blood, determination of the content of leukocytes, platelets, hemoglobin, blood counts, liver and renal function tests, electrolytes and blood serum.Re drug should not be administered for as long as the content of serum creatinine is reduced to 1.5 mg / 100 ml or less and / or blood urea nitrogen is reduced to 25 mg / 100 ml or less of blood platelet content is 100 000 / mm³, leukocytes – not less than 4000 / mm³.
- With the development of allergic reactions in the form of facial edema, bronchospasm, tachycardia and hypotension should use epinephrine, corticosteroids and drugs antigisgaminnye.
- When using Cisplatin must be observed all the usual regulations adopted for the application of cytotoxic drugs.
- In case of contact with the drug in their eyes, rinse immediately with plenty of water or sodium chloride solution. In case of contact with the drug on the skin, rinse immediately with a place of contact with plenty of water. In case of inhalation of the drug or getting it in your mouth you should immediately consult a doctor.
Concentrate for solution for infusion at 20 ml / 100 ml and 10mg / 50mg in orange glass bottles. 1 bottle in a cardboard box with the accompanying instructions for use.
List A. Store at 15 ° – 25 ° C, protected from light and out of reach of children.
Do not use the drug after the expiry date stated on the package.