Cisplatin concentrate for the preparation of the solution for the infusion of 0.5 mg/ml 20 ml

Indications and usage

Cisplatin, usually in combination Chemotherapy, is widely used in the treatment of the following solid tumors:

- germ cell tumors of women and men;

- cancer of the ovaries and testicles;

- small cell and non-small cell lung cancer;

- squamous cell carcinoma of the head and neck;

- bladder cancer.

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

- cervical cancer;

- osteosarcoma;

- melanoma;

- neuroblastoma;

- esophageal carcinoma.

Cisplatin can be used both as monotherapy and in combination with other cytotoxic drugs in various doses, depending on the regimen. When individual dose should be guided by the data of special literature. Cisplatin is injected in / in or when indicated (intraperitoneal tumors) in the abdominal cavity.

Cisplatin in monotherapy and in combination with other chemotherapy drugs is usually administered in a dose of 50-100 mg / m² in the form of intravenous infusion every 3-4 weeks or 15-20 mg / m² IV drip daily for 5 days every 3-4 weeks.

Recommendations for the preparation and administration of solutions for IV infusions

In order to stimulate diuresis (up to 100 ml / h) and to minimize the nephrotoxic effect of the preparation, hydration is carried out. Before the introduction of cisplatin in / drip injected up to 2 liters of fluid. Excessive fluid intake and maintenance of diuresis must be observed for 24 hours. If intensive hydration is insufficient to maintain adequate diuresis, an osmotic diuretic can be administered (for example, mannitol).

Cisplatin is introduced into / in the drip at a rate not exceeding 1 mg / min. Long-term infusions are carried out for 6-8-24 hours, provided sufficient diuresis is administered before the administration and during the administration of the drug.

Cisplatin is diluted in one of the following infusion solutions: 0.9% sodium chloride solution; 0.9%, 0.45% or 0.3% solution of sodium chloride in 5% glucose solution. Diluted solutions of the drug are stable for 6-8 hours at a temperature not exceeding 25 ° C in a dark place.

Note: Since aluminum reacts with cisplatin and inactivates it, and also causes the formation of a precipitate, it is very important when preparing and when administering cisplatin not to use needles and other equipment containing aluminum.

Adverse reactions

Urogenital: nephrotoxicity is cumulative in nature and is the main toxic factor limiting the dose of cisplatin. Kidney damage, which is accompanied by damage to the renal tubules, may first be detected in the second week after a dose and manifest an increase in serum creatinine, urea, and uric acid and / or a decrease in creatinine clearance.Renal toxicity, as a rule, is insignificant or moderately severe and is reversible at usual doses of Cisplatin.

From the electrolyte balance: hypomagnesemia, hypocalcemia, hyponatremia, hypokalemia and hypophosphatemia. Hypomagnesemia and / or hypocalcemia may manifest clinically increased muscle sensitivity or seizures, tremor, carpopedal spasm (cramps in the hands and feet), and / or tetany. Hyponatremia is usually caused by the syndrome of inadequate production of antidiuretic hormone.

From the digestive tract: nausea and vomiting, which usually begin during the first hour of therapy and last for 24 hours or more, occur in almost all patients. These side effects are only partially eliminated by the use of standard antiemetic drugs. The severity of these symptoms can be reduced by dividing the total dose, calculated per cycle of therapy, into smaller doses, which are administered 1 time per day for five days.

Of the other often observed adverse events from the gastrointestinal tract marked pain in the abdomen, diarrhea and constipation.

Hemic and lymphatic: during treatment with cisplatin, myelosuppression often develops, but in most cases it is expressed slightly or moderately, and at the use of ordinary doses is reversible. The lowest levels of leukocytes and platelets are usually observed from the 18th to the 23rd day after administration; in most patients, these indicators are restored to the 39th day. Anemia may also occur.

On the part of the hearing system: unilateral or bilateral tinnitus, with or without loss of hearing, occurs in approximately 10% of patients receiving cisplatin, usually this side effect is reversible. It has been established that damage to the organ of hearing is dose-dependent and cumulative, and this side effect is more often observed in patients of very young or old age. There are reports of the toxic effect of the drug on the vestibular apparatus.

Nervous system: peripheral neuropathy occurs infrequently. Usually they have a sensory nature (for example, paresthesias of the upper and lower extremities), but motor disturbances may also occur (decreased reflexes and weakness in the lower extremities). Vegetative neuropathy, convulsions, slurred speech, loss of taste and memory loss can also occur. The development of Lermitte's symptom, spinal myelopathy, and autonomic neuropathy have been reported. Treatment with the drug should be discontinued at the first appearance of such symptoms.

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

From the system of view: in rare cases, there is optic neuritis, swelling of the nipple of the optic nerve, cortical blindness. There may also be a change in the perception of colors, especially in the yellow-blue part of the spectrum. The only change in the fundus can be irregular pigmentation of the retina in the area of ​​the yellow spot.

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

Toxic effect on the liver: occasionally there may be slight and transient increases in the level of ACT, ALT and serum bilirubin.

Other side effects: disorders of the cardiovascular system (ischemic heart disease, myocardial infarction, stroke, congestive heart failure, arrhythmias, orthostatic hypotension, thrombotic microangiopathy, cerebral arteritis platinum line. If the drug gets under the skin, the development of phlebitis, inflammation of the subcutaneous fat and skin necrosis is possible.

Reported cases of spermatogenesis and azoospermia.

Contraindications

- individual intolerance to cisplatin or other compounds containing platinum;

- impaired renal function (serum creatinine level more than 115 mmol / l);

- inhibition of bone marrow hematopoiesis;

- pregnancy and lactation period.

Carefully: hearing loss, polyneuritis, acute infectious diseases, chicken pox (including recent or recent contact with a patient), herpes zoster, a history of gout, nephrolithiasis, radiation or chemotherapy in the anamnesis.

Pregnancy and Breastfeeding

Cisplatin is contraindicated during pregnancy and lactation.

Cisplatin was found in the milk of mammals during animal experiments.

In experimental studies established teratogenic and embryotoxic effect of cisplatin.

The drug should be used under the supervision of a physician with experience in the use of anticancer drugs.

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

Men receiving cisplatin therapy should use barrier methods of contraception.

Patients with cisplatin treatment should be periodically examined by a neurologist. With obvious symptoms of toxic effects on the central nervous system, cisplatin therapy should be discontinued.

Before starting therapy, audiometry should be performed, and in cases where symptoms of damage to the organ of hearing appear or clinical hearing impairments are detected, repeated audiometry is indicated. For clinically significant hearing impairment, dosage adjustment or withdrawal of therapy may be required.

In the course of treatment with cisplatin, periodic blood tests, determination of white blood cells, platelets, hemoglobin, blood cells, renal and hepatic functional tests, as well as the level of electrolytes in blood serum are necessary.

Repeatedly, the drug should not be administered until the serum creatinine content drops to 1.5 mg / 100 ml or less and / or the blood urea nitrogen drops to 25 mg / 100 ml or less, the platelet count in the blood does not become 100,000 / mkl, leukocytes - not less than 4000 / mkl.

With the development of allergic reactions in the form of swelling of the face, bronchospasm, tachycardia and hypotension, adrenaline, corticosteroids and antihistamines should be used.

When using cisplatin, all the usual instructions adopted for the use of cytotoxic drugs should be followed. Dilution of the drug should be carried out in a specially designated area (preferably in a laminar cabinet for working with cytotoxic substances). When working with cisplatin, you should wear a protective gown, mask, gloves and protect your eyes. Pregnant women should not work with cisplatin.

In case of contact with the eyes, wash them immediately with plenty of water or sodium chloride solution. In case of contact with the skin, immediately rinse the place of contact with the drug with a large amount of water. In the case of inhalation of the drug or getting it into the mouth, you should immediately consult a doctor.

During treatment, it is not recommended to vaccinate the patient, due to the possibility of intensifying the process of replication of the vaccine virus or a decrease in the production of antibodies in response to the introduction of the vaccine during vaccination with live or inactivated vaccines. The interval between the end of the use of the drug and vaccination with live or inactivated vaccines is from 3 to 12 months. The patient should avoid contact with people who have received vaccination, or it is recommended to wear a protective mask. Also not recommended vaccination of family members of the patient.

Influence on ability to drive vehicles and mechanisms

Depending on the individual sensitivity, cisplatin may adversely affect the ability to drive vehicles and mechanisms.

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

Antidote in case of drug overdose Cisplatin is unknown. The effect, at least partial, is achieved only through hemodialysis, if it is used within the first three hours after the overdose, since platinum is quickly bound to plasma proteins . Symptomatic therapy is used to eliminate the symptoms of overdose.

Simultaneous or sequential use of cisplatin with antibiotic aminoglycosides (gentamicin, kanamycin, streptomycin) or with other potentially nephrotoxic drugs (for example, amphotericin B) can potentiate its nephrotoxic and ototoxic effects.

“Loopback” diuretics (furosemide, clopamide, ethacrynic acid) may increase the ototoxicity of cisplatin.

It is known that cisplatin may interfere with kidney bleomycin and Methotrexate (possibly due to nephrotoxic action caused by cisplatin) and increase the toxicity of these drugs.

With the simultaneous use of cisplatin, hexamethylmelamine and Pyridoxine in the treatment of ovarian cancer, a decrease in the duration of remission was noted. In patients receiving cisplatin and anticonvulsant drugs, the concentration of the latter in the serum may decrease to subtherapeutic values. Cisplatin may cause an increase in the concentration of uric acid in the blood. Therefore, in patients who are simultaneously taking medications for the treatment of gout, such as Allopurinol, colchicine, probenecid or sulfinpyrazone, it may be necessary to adjust the dosage of these drugs in order to control hyperuricemia and gout attacks.

When cisplatin interacts with aluminum, a precipitate forms.

The drug should be kept out of the reach of children at a temperature of 15 ° to 25 ° C.