Cisplatin-Teva concentrate for infusion solution 0.5mg/ml vials, 100ml

Composition

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1 ml contains:

Active ingredients:

cisplatin 0.5 mg.

Auxiliary substances:

sodium chloride,

hydrochloric acid or sodium hydroxide (to correct the pH level),

d/i water.

In a dark glass bottle of 100 ml of the solution.

In a cardboard box 1 bottle.

Pharmacological action

Pharmacodynamics

Cisplatin (cis-diamindihlorplatin) is an antitumor drug containing the heavy metal platinum.

Cisplatin has properties similar to those of bifunctional alkylating agents that form inter-strand and inter-strand cross-links in DNA, thereby disrupting its functions, which leads to cell death; however, the drug does not have cyclic and phase specificity. It has immunosuppressive and radiosensitizing properties.

Pharmacokinetics

After a rapid intravenous infusion (15 minutes – 1 hour), the appearance of cisplatin in the blood plasma and its peak concentration is determined immediately after use. With intravenous infusion for 6-24 hours, the concentration of the drug in plasma increases gradually during the infusion, reaching a maximum by the end of use.

Cisplatin is characterized by extensive distribution in body fluids and tissues, with the highest concentrations being achieved in the kidneys, liver, and prostate. Platinum released from cisplatin binds rapidly to tissue and plasma proteins. Two hours after the end of the three-hour infusion,90% of plasma platinum is in a protein-bound state. Cisplatin has the ability to accumulate in the body and be detected in some tissues for another six months after the last dose of the drug is administered. Cisplatin biotransformation is carried out by rapid nonenzymatic transformation with the formation of inactive metabolites. Only cisplatin, which is not bound to proteins, or its platinum-containing metabolites have a cytotoxic effect.

The half-life of total platinum has a very wide individual variability and ranges from 2-72 hours in healthy people, and 1-240 hours in severe renal failure. Cisplatin is mainly excreted in the urine. Cisplatin can be removed from the systemic circulation by dialysis, but only within the first 3 hours after use of the drug.

Indications

Cisplatin, usually as part of combination chemotherapy regimens, is widely used in the treatment of the following solid tumors:

• germinogenic tumors of women and men;
• ovarian and testicular cancer;
• lung cancer;
• head and neck tumors.

In addition, cisplatin has antitumor activity in the following types of tumors: :

• cervical cancer;
• bladder cancer;
• osteosarcoma;
• melanoma;
• neuroblastoma;
• esophageal cancer.

Contraindications

• Individual intolerance to cisplatin or other platinum-containing compounds;
• impaired renal function (serum creatinine level more than 115 mmol / liter);
• inhibition of bone marrow hematopoiesis;
• heart failure;
• pregnancy and lactation;
• generalized infections.

Side effects

From the urinary system: nephrotoxicity (cumulative in nature and is the main toxic factor limiting the dose of Cisplatin). Renal lesions that are accompanied by damage to the renal tubules may first be detected in the second week after use of the dose and manifest as an increase in serum creatinine, urea, uric acid and/or a decrease in creatinine clearance. Renal failure is usually mild to moderate and is reversible at normal doses of Cisplatin.

From the digestive system: nausea and vomiting, which usually begin within the first hour of therapy and continue for 24 hours or more, occur in 65% of patients. These side effects are only partially eliminated with the use of standard antiemetic drugs. The severity of these symptoms can be reduced by dividing the total dose calculated for the treatment cycle into smaller doses that are administered once a day for five days.

Other commonly reported gastrointestinal side effects include abdominal pain, diarrhea, and constipation. Occasionally, there may be slight and transient increases in the level of AST and ALT in the blood serum.

From the hematopoietic system: often-myelosuppression, (in most cases it is expressed slightly or moderately and with the use of normal doses is reversible). The lowest levels of white blood cells and platelets are usually detected after about 2 weeks; their initial level in most patients is restored within 4 weeks. Anemia may also occur.

From the side of the hearing system: unilateral or bilateral tinnitus, with or without hearing loss, is observed in about 10% of patients; usually this side effect is reversible. It was found that the damage to the hearing organ is dose-dependent and cumulative, and this side effect is more often observed in patients of very young or senile age. There are reports of toxic effects of the drug on the vestibular apparatus.

From the central nervous system and peripheral nervous system: peripheral neuropathies occur infrequently. They are usually sensory in nature (for example, paresthesia of the upper and lower extremities), but motor disorders can also occur (reduced reflexes and weakness in the lower extremities). There may also be autonomic neuropathy, seizures, slurred speech, loss of taste, and memory loss. Lermitt’s syndrome (spinal column myelopathy and autonomic neuropathy) has been reported in the literature. Treatment should be discontinued at the first appearance of these symptoms.

On the part of the immune system: sometimes there are allergic reactions, manifested in the form of redness and swelling of the face, wheezing in the lungs, tachycardia and a decrease in blood pressure. These reactions may occur within a few minutes after the start of cisplatin use. In rare cases, urticaria and maculopapular skin rash may occur.

From the side of the visual system: in rare cases, neuritis of the optic nerve, edema of the optic disc, cortical blindness are noted. There may also be changes in color perception, especially in the yellow-blue part of the spectrum. The only change in the fundus may be irregular retinal pigmentation in the macular area.

These side effects are usually reversible and disappear after discontinuation of the drug.

Electrolyte disturbances: hypomagnesemia, hypocalcemia, and hypokalemia. Hypomagnesemia and/or hypocalcemia may manifest clinically as increased muscle sensitivity or seizures, tremor, carpopedal spasm (hand and foot cramps), and / or tetany. Hyponatremia is possible due to the syndrome of inadequate production of antidiuretic hormone.

Local reactions: if the drug gets under the skin, phlebitis, cellulite and skin necrosis may develop.

Other: cardiovascular disorders (ischemic heart disease, congestive heart failure, arrhythmias, orthostatic hypotension, thrombotic microangiopathy, etc. ), hyperuricemia, minor alopecia, myalgia, fever, and platinum gingival line. There were cases of spermatogenesis and azoospermia disorders.

Interaction

Concomitant or sequential use of cisplatin with aminoglycoside antibiotics (gentamicin, kanamycin, streptomycin) or with other potentially nephrotoxic drugs (for example, amphotericin B) may potentiate its nephrotoxic and ototoxic effects.

Loop diuretics (furosemide, clopamide, etacric acid) may increase the ototoxicity of cisplatin.

It is known that cisplatin may interfere with the renal excretion of bleomycin and methotrexate (possibly due to cisplatin-induced nephrotoxic effects) and increase the toxicity of these drugs.

In patients receiving cisplatin and anticonvulsants, the concentration of the latter in the blood serum may decrease to subtherapeutic values.

Cisplatin can cause an increase in the concentration of uric acid in the blood. Therefore, patients who are taking concomitant medications for the treatment of gout, such as allopurinol, colchicine, probenecid, or sulfinpyrazone, may need to adjust the dosage of these medications to control hyperuricemia and gout attacks.

How to take, course of use and dosage

Cisplatin can be used both as monotherapy and in combination with other cytostatics in various doses, depending on the treatment regimen. Individual dose selection should be guided by the data of the specialized literature.

Cisplatin is administered intravenously or when indicated (intraperitoneal tumors) in the abdominal cavity.

Cisplatin in monotherapy or in combination with other chemopreparations is administered at a dose of 50-100 mg/m%^%2 as an intravenous infusion every 3-4 weeks or 15-20 mg/m%^%2 IV drip daily for 5 days every 3-4 weeks.

In order to stimulate diuresis (up to 100 ml/h) and to maximize the reduction of the nephrotoxic effect of the drug, hydration is performed. Before the introduction

of Cisplatin, up to 2 liters of liquid (0.9% sodium chloride solution or 5% dextrose solution) are administered intravenously. After the end of the infusion,400 ml of 0.9% sodium chloride solution or 5% dextrose solution is additionally administered. Copious fluid intake and maintenance of diuresis should be observed within 24 hours.If intensive hydration is not sufficient to maintain adequate diuresis, an osmotic diuretic (for example, mannitol) can be administered. Cisplastin is administered intravenously at a rate of no more than 1 mg/min. Long-term infusions are performed for 6 to 8 to 24 hours, provided that sufficient diuresis occurs before and during use of the drug.

Cisplatin is diluted in 0.9% sodium chloride solution to a concentration of 1 mg / ml. Cisplastin lyophysilate should first be dissolved in 10-25 ml of water for injection.

Do not use dextrose (glucose) solutions to dilute Cisplatin.

Note: Since aluminum reacts with cisplatin and inactivates it, as well as causes sediment formation, it is very important not to use needles and other equipment containing aluminum when preparing and administering Cisplatin.

Overdose

The main expected complications of overdose are impaired renal function, liver function, visual impairment (including retinal detachment) and hearing impairment (deafness), severe myelosuppression, indomitable vomiting, and/or severe neuritis. Overdose can be fatal.

The antidote to cisplatin is unknown. Treatment is symptomatic. A partial effect can be achieved by hemodialysis performed within the first three hours after an overdose.

Special instructions

Cisplatin should be administered under the supervision of a physician experienced in the use of anticancer drugs.

Men and women of childbearing age should use reliable methods of contraception during Cisplatin treatment.

Patients treated with cisplatin should be periodically examined by a neurologist. If there are obvious symptoms of toxic effects on the central nervous system, Cisplatin therapy should be discontinued.

Audiometry should be performed before starting therapy, and in cases where symptoms of hearing damage appear or clinical hearing disorders are detected, repeated audiometry is indicated. In cases of clinically significant hearing impairment, dosage adjustment or discontinuation of therapy may be required.

During treatment with Cisplatin, a periodic blood test is required, determining the content of white blood cells, platelets, hemoglobin, formed blood elements, renal and hepatic function tests, as well as the level of electrolytes in the blood serum.

When using Cisplatin, all the usual instructions for the use of cytotoxic drugs should be followed. If the drug gets into the eyes, they should be immediately rinsed with plenty of water or 0.9% sodium chloride solution. If the drug gets on the skin, it is necessary to immediately wash the place of contact with the drug with a large amount of water. If the drug is inhaled or enters the mouth, consult a doctor immediately.

Form of production

Solution for injection

Storage conditions

Store at a temperature not exceeding 25°C in a place protected from light and out of the reach of children.

Shelf

life is 2 years.

Active ingredient

Cisplatin

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution