Cisplatin-LNS, 0.5 mg/ml 50 ml

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Indications

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

– germ cell tumors in women and men;

– ovarian and testicular cancer;

– Small cell and non-small cell lung cancer;

– squamous cell head and neck cancer;

– bladder cancer.

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

– cervical cancer;

– osteosarcoma;

– melanoma;

– neuroblastoma;

– esophageal cancer.

Active ingredient

Composition

1 ml of the concentrate contains:

The active substance: cisplatin in terms of 100% substance – 0.0005 g.

Auxiliary substances: sodium chloride in terms of 100% of substance – 0.009 g; sodium hydroxide in terms of 100% of substance or hydrochloric acid – to pH 3.2; water for injection – up to 1 ml.

How to take, the dosage

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

Cisplatin is given intravenously or when indicated (intraperitoneal tumors) in the abdomen.

Cisplatin in monotherapy and in combination with other chemotherapies is usually administered at a dose of 50-100 mg/m2 as an intravenous infusion every 3-4 weeks or 15-20 mg/m2 intravenous drip daily for 5 days every 3-4 weeks.

Recommendations for preparation and administration of solutions for intravenous infusion

Cisplatin is administered intravenously by IV drip at a rate of no more than 1 mg/min. Prolonged infusions are given over a period of 6-8-24 hours, provided there is sufficient diuresis before and during administration of the drug.

Cisplatin is diluted in 0.9% sodium chloride solution to a concentration of at least 1 mg/ml. The diluted solutions of the drug are stable for 6-8 hours at a temperature not exceeding 25 ° C in a light-protected place.

Note: Because aluminum reacts with and inactivates cisplatin and causes precipitate formation, it is very important not to use needles or other equipment containing aluminum when preparing and administering cisplatin.

Interaction

A concomitant use of cisplatin, altretamine and pyridoxine in the treatment of ovarian cancer was noted to shorten the duration of remission.

Special Instructions

– The drug should be used under the supervision of a physician experienced in the use of antitumor drugs.

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

– Men receiving cisplatin therapy should use barrier methods of contraception.

– Patients on cisplatin treatment should be periodically evaluated by a neurologist. If there are clear symptoms of central nervous system (CNS) toxicity, cisplatin therapy should be discontinued.

– Audiometry should be performed prior to initiating therapy, and repeat audiometry is indicated if there are symptoms of hearing impairment or clinical hearing loss. Dose adjustment or discontinuation of therapy may be necessary if clinically significant hearing loss occurs.

– During treatment with cisplatin, periodic general blood tests should be performed to determine white blood cell count, platelet count, hemoglobin, renal and hepatic function tests, and serum electrolyte concentrations.

The drug should not be administered again until serum creatinine decreases to 1.5 mg/100 ml or less, and/or blood urea nitrogen decreases to 25 mg/100 ml or less, blood platelet count is 100,000/μL, leukocyte count is at least 4000/μL.

– If allergic reactions develop in the form of facial edema, bronchospasm, tachycardia and decreased blood pressure, adrenaline, corticosteroids and antihistamines should be used.

– When using cisplatin, all routine instructions for the use of cytotoxic drugs should be followed.

– If the drug gets into the eyes, the eyes should be rinsed immediately with plenty of water or sodium chloride solution. If the drug gets on the skin, immediately rinse the place of contact with the drug with plenty of water. In case of inhalation of the drug or ingestion it is necessary to seek medical advice immediately.

During treatment, it is necessary to refrain from engaging in potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

– Individual intolerance to cisplatin or other compounds containing platinum;

– Renal dysfunction (serum creatinine concentration greater than 115 µmol/L);

– inhibition of medullary hematopoiesis;

– pregnancy and lactation;

– generalized infections.

Acute infections of viral (varicella, including recent or recent exposure, herpes zoster), fungal or bacterial genesis; hyperuricemia (including those manifested by gout and/or urate nephrolithiasis), nephrourolithiasis, polyneuritis, suppression of medullary hematopoiesis (including against the background of prior radiation or chemotherapy).

Side effects

Urinary system disorders

Nephrotoxicity is cumulative in nature and is the major dose-limiting toxicity of cisplatin. Renal lesions, which are accompanied by damage of renal tubules, may be first detected in the second week after dose administration and are manifested by increased serum creatinine, urea, uric acid concentrations and/or decreased creatinine clearance. Renal toxicity is generally mild to moderate and reversible at normal doses of Cisplatin.

Electrolyte balance disorders

Hypomagnesemia, hypocalcemia, hyponatremia, hypokalemia and hypophosphatemia. Hypomagnesemia and/or hypocalcemia may manifest clinically with increased muscle sensitivity or seizures, tremor, carpopedal spasm (cramps in the hands and feet) and/or tetany. Hyponatremia is usually due to a syndrome of inadequate production of antidiuretic hormone.

Gastrointestinal side effects

Nausea and vomiting, which usually start within the first hour of therapy and last for 24 hours or more, occur in almost all patients. These side effects are only partially resolved with standard antiemetics. The severity of these symptoms can be reduced by dividing the total dose calculated for a cycle of therapy into smaller doses administered once daily for five days.

Other commonly observed gastrointestinal adverse events include abdominal pain, diarrhea, and constipation.

Hematopoietic disorders

Myelosuppression often occurs with cisplatin therapy, but in most cases it is mild to moderate in severity and is reversible with normal doses. The lowest leukocyte and platelet counts are usually observed from day 18 to day 23 after administration; most patients recover by day 39. Anemia may also be observed.

Hearing and balance disorders

Unilateral or bilateral tinnitus, with or without hearing loss, occurs in approximately 10% of patients treated with cisplatin, and this side effect is usually reversible. Hearing damage has been found to be dose-dependent and cumulative, and this side effect is more common in very young or elderly patients. There are reports of a toxic effect of the drug on the vestibular system.

CNS and peripheral nervous system disorders

Peripheral neuropathies occur infrequently. Usually they are sensory in nature (e.g., paresthesias of the upper and lower extremities), but motor disorders (decreased reflexes and weakness in the lower extremities) may also occur. Autonomic neuropathy, seizures, slurred speech, loss of taste, and memory loss may also occur. The development of Lhermitte’s symptom, myelopathy of the spinal column and neuropathy of the autonomic nervous system has been reported. Treatment with the drug should be discontinued at the first occurrence of such symptoms.

Hypersensitivity

Sometimes there are allergic reactions manifested as redness and swelling of the face, wheezing in the lungs, tachycardia and arterial hypotension. These reactions may occur within a few minutes after the start of cisplatin administration. In rare cases, urticaria and maculopapular skin rash may occur.

Visual organs

In rare cases, optic neuritis, edema of the optic nerve papilla, cortical blindness have been observed. There may also be changes in color perception, particularly in the yellow-blue part of the spectrum. The only ocular changes may be irregular retinal pigmentation in the yellow spot area.

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

Toxic effects on the liver

Slight and transient increases in serum aspartate aminotransferase (ACT), alanine aminotransferase (ALT) and bilirubin concentrations may occasionally be noted.

Other side effects

Cardiovascular system disorders (coronary heart disease, myocardial infarction, stroke, chronic heart failure, arrhythmias, orthostatic hypotension, thrombotic microangiopathy, cerebral arteritis), hyperuricemia, increased serum amylase concentration, minor alopecia, myalgia, fever, hiccups and gum line platinum.

If the drug gets under the skin, phlebitis, inflammation of the subcutaneous fatty tissue and skin necrosis may develop.

Cases of impaired spermatogenesis and azoospermia have been reported.

Overdose

The main expected complications of overdose are renal, hepatic, visual (including retinal detachment) and hearing (deafness) disorders, severe myelosuppression, uncontrollable nausea and vomiting and/or neuritis. In case of overdose, lethal outcome is possible.

An antidote in case of overdose of Cisplatin is unknown. The effect, at least partial, is achieved only with hemodialysis, if it is used within the first three hours after overdose, because platinum quickly binds to plasma proteins. Symptomatic therapy is used to eliminate the symptoms of overdose.

Pregnancy use