Composition, form of production and packaging
Concentrate for the preparation of a solution for infusions and intraperitoneal administration of light yellow color with a greenish tinge, transparent.
1 ml
cisplatin 1 mg
Excipients: sodium chloride - 9 mg, hydrochloric acid (0.1 mol / l) - up to pH4, water d / u - up to 1 ml.
10 ml - bottles of glass (1) - packs of cardboard.
Concentrate for the preparation of a solution for infusions and intraperitoneal administration of light yellow color with a greenish tinge, transparent.
1 ml
cisplatin 1 mg
Excipients: sodium chloride - 9 mg, hydrochloric acid (0.1 mol / l) - up to pH4, water d / u - up to 1 ml.
50 ml - bottles of glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
The product description was approved by the manufacturer for the 2009 print edition.
PHARMACHOLOGIC EFFECT
Dysplanor (cisplatin) is an antitumor drug containing a heavy metal platinum.
Cisplatin possesses properties similar to the properties of bifunctional alkylating agents forming interstitial and interstitial crosslinks in DNA, thereby violating its functions and inhibiting the synthesis, which leads to cell death; the preparation does not have cyclic and phase specificity. To a lesser extent suppresses the synthesis of protein and RNA. Has immunosuppressive and radiosensitizing properties.
Platinum complexes with cis-arrangement of halogen atoms can form stable chelate complexes with purine and pyrimidine components of the nucleic acid molecule, thus forming bonds within one filament or parallel strands of a double helix of DNA. Antitumor effect is partly promoted by immunosuppressive effect. The therapeutic effect persists for several days after administration.
PHARMACOKINETICS
After the introduction of rapid intravenous infusions (15 minutes - 1 hour), the maximum concentration of cisplatin is achieved immediately. With intravenous infusion for 6-24 hours the concentration of the drug in the plasma increases gradually during the infusion, reaching a maximum at the end of the injection.
Cisplatin is characterized by extensive distribution in body fluids and in. tissues; with the highest concentrations being achieved in the kidneys, liver and prostate gland. Cisplatin penetrates into breast milk. Cisplatin poorly penetrates into the cerebrospinal fluid.
Platinum, released from cisplatin, quickly binds to tissue and plasma proteins. Two hours after the end of the three-hour infusion, 90% of the platinum in the plasma is in the protein-bound state. Cisplatin has the ability to accumulate in the body and is found in some tissues for another six months after the administration of the last dose of the drug.
Biotransformation of cisplatin is carried out by rapid non-enzymatic transformation with formation of inactive metabolites. Cytotoxic action has only cisplatin not associated with proteins, or its platinum-containing metabolites.
After intravenous infusion, the half-life of cisplatin is about 30 minutes.
Cisplatin is excreted mainly by the kidneys. Cisplatin can be excreted from the systemic blood flow by dialysis, but only within the first 3 hours after the administration of the drug.
INDICATIONS
Dysplanor, usually as part of combined chemotherapy, is widely used in the treatment of the following solid tumors:
- germinogenic tumors in men and women;
ovarian and testicular cancer;
- lung cancer;
- Head and neck tumors.
In addition, the Displanor has antitumor activity in the following types of tumors:
- cervical cancer;
- bladder cancer;
osteosarcoma;
- melanoma;
- a neuroblastoma;
- esophageal carcinoma.
DOSING MODE
Dysplanor can be used as a monotherapy, or in combination with other cytostatics in different doses depending on the scheme of therapy. For individual dose selection, reference should be made to the literature.
Dysplanor is administered intravenously in the form of infusion or with indications (intraperitoneal tumors) in the abdominal cavity.
Dysplanor in monotherapy or in combination with other chemotherapeutics is usually administered at a dose of 50-100 mg / m 2 as an intravenous infusion every 3-4 weeks or 15-20 mg / m 2 intravenously drip daily for 5 days every 3-4 weeks.
To stimulate diuresis (up to 100 ml / h) and to minimize the nephrotoxic effect of the drug, hydration is performed. Before the introduction of the drug Dysplanor intravenously drip up to 2 liters of fluid (0.9% solution of sodium chloride or 5% solution of dextrose). After the infusion of the drug is completed, 400 ml of a 0.9% solution of sodium chloride or a 5% solution of dextrose are additionally added. Fluid intake and maintenance of diuresis must be observed within 24 hours. If intensive hydration to maintain adequate diuresis is not sufficient, you can introduce an osmotic diuretic (eg, mannitol).
Dysplanor is administered intravenously drip at a rate of no more than 1 mg / min. Prolonged infusions are carried out within 6-8-24 hours provided sufficient diuresis before and during administration of the drug.
Dysplanor is dissolved in 2 liters of 0.9% sodium chloride solution.
Note: Since aluminum reacts with cisplatin and inactivates it, and also causes sediment formation, it is very important not to use needles and other equipment containing aluminum when preparing and administering the Displanor drug.
SIDE EFFECT
From the side of the urinary system: nephrotoxicity (is cumulative and is the main toxic factor limiting the dose of the drug Displanor). Renal lesions that are accompanied by damage to the renal tubule can first be detected in the second week after dosing, and may be manifested by an increase in the concentration of creatinine, urea, uric acid in the blood serum and / or a decrease in creatinine clearance. Renal insufficiency, as a rule, is insignificant or moderately pronounced and is reversible at usual doses of preparation Dysplanor.
On the part of the digestive system: nausea and vomiting, which usually begin within the first hour of therapy and last 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 therapy cycle into smaller doses that are administered once a day for five days.
Of the other frequently observed adverse events from the gastrointestinal tract, abdominal pain, diarrhea and constipation are noted. Occasionally, minor and transient increases in the concentration of aspartate aminotransferase and alanine aminotransferase in serum can be noted.
On the part of the hematopoiesis system: often - myelosuppression (in most cases it is expressed slightly or moderately, and when applied to conventional doses is reversible). The lowest content of leukocytes and platelets, usually found after about 2 weeks; their initial value in most patients is restored within 4 weeks. Anemia can also occur.
On the part of the system of the organ of hearing and balance: one-sided or bilateral tinnitus, with loss of hearing or without loss, is observed in about 10% of patients, usually this side effect is reversible. It is established 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 a toxic effect of the drug on the vestibular apparatus.
From the side of the nervous system: peripheral neuropathies occur infrequently. They are usually sensory in nature (for example, paresthesia of the upper and lower extremities), but also motor disorders (decreased reflexes and weakness in the lower limbs) may occur. Also, vegetative neuropathy, convulsions, slurred speech can be noted. loss of taste and loss of memory. In the literature, the development of the Lermitt syndrome (myelopathy of the vertebral column and neuropathy of the autonomic nervous system) was reported. Treatment should be discontinued at the first appearance of these symptoms.
Allergic reactions: sometimes there are allergic and anaphylactoid reactions manifested in the form of redness and face swelling, bronchospasm, dyspnea, tachycardia, lowering of arterial pressure and anaphylactic shock. These reactions can occur within a few minutes after the onset of cisplatin administration. In rare cases, there may be hives and a maculopapular skin rash.
From the side of the organ of vision: in rare cases, neuritis of the optic nerve, edema of the optic nerve disk, cortical blindness are noted. 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 uneven pigmentation of the retina in the area of ​​the yellow spot. These side effects are usually reversible and disappear after drug withdrawal.
From the electrolyte balance: hypomagnesemia, gilocalcemia and hypokalemia. Hypomagnesemia and / or hypocalcemia can be manifested clinically by increased muscle sensitivity or seizures, tremor, carpopedic spasm (cramps in hands and feet) and / or tetany. Possible hyponatremia, caused by the syndrome of inadequate production of antidiuretic hormone.
From the cardiovascular system: myocardial infarction, stroke, arteritis of the cerebral vessels, arrhythmias, bradycardia, tachycardia, thrombotic microangiopathy, orthostatic hypotension.
Other: hyperuricemia, minor alopecia, myalgia, fever, and plaque gum line.
There are reports of the occurrence of Raynaud's syndrome with a combination of bleomycin and vinblastine with or without cisplatin.
If the product gets under the skin, it is possible to develop phlebitis, inflammation of the subcutaneous tissue and skin necrosis.
Cases of spermatogenesis and azoospermia are noted.
CONTRAINDICATIONS
- impaired renal function (serum creatinine concentration more than 115 Ојmol / l);
- oppression of bone marrow hematopoiesis;
- heart failure;
- pregnancy and the period of breastfeeding;
- generalized infections;
- hearing loss;
- hypersensitivity to cisplatin or other compounds containing platinum, as well as to any component of the drug.
With caution: acute infectious diseases of the viral (chicken pox, including the recently transferred or recent contact with the patient, herpes zoster), fungal or bacterial genesis; hyperuricemia (including manifested by gout and / or urate nephrourolythiasis), nephrourolythiasis, polyneuritis.
SPECIAL INSTRUCTIONS
Administration of the drug Dysplanor should be carried out under the supervision of a doctor who has experience using antitumor drugs.
Men and women of childbearing age during treatment with the drug Dysplanor should use reliable methods of contraception.
Patients on the background of treatment with the drug Dysplanor should periodically be examined by a neurologist. With obvious symptoms of toxic effects on the central nervous system, the drug Dysplanor should be discontinued.
Before the start of therapy, audiometry should be performed, and in cases where there are symptoms of hearing damage or clinical hearing impairments, repeated audiometry is indicated. In clinically significant hearing disorders, dose adjustment or treatment can be required.
In the process of treatment with the drug Dysplanor it is necessary to periodically perform a general blood test with the definition of the content of leukocytes, platelets, hemoglobin. It is also necessary to monitor the functional work of the kidneys and liver, as well as the concentration of electrolytes in the blood serum.
When using the drug Dysplanor, all the usual instructions adopted for the use of cytotoxic drugs should be observed.
In case of anaphylactic or anaphylactoid reactions, discontinuation should be stopped immediately and appropriate therapy started. In some cases, the introduction of platinum salts reported the occurrence of cross-allergic reactions.
If the product gets into the eyes, they must be washed immediately with a large amount of water or with 0.9% sodium chloride solution. In case of contact with the skin, immediately contact the product with plenty of water. If the product is inhaled or if it gets into the mouth, immediately consult a doctor.
The prepared cisplatin solution should be protected from exposure to light and stored at 15-25 В° C for 24 hours. Do not put the solution in a refrigerator, cooling can lead to precipitation. Unused solution should be disposed of.
Influence on the ability to drive and work with machinery.
Cisplatin does not directly affect the ability to drive and work with machinery. However, side effects from the central nervous system and sensory organs can reduce the speed of psychomotor reactions, which can affect the ability to drive and work with mechanisms.
OVERDOSE
The main anticipated complications of overdose are renal, hepatic, visual impairment (including retinal detachment) and hearing (deafness), severe myelosuppression, indomitable vomiting and / or severe neuritis. In case of an overdose, a lethal outcome is possible.
The antidote to cisplatinum is unknown. Treatment is symptomatic. A partial effect can be achieved with hemodialysis performed within the first three hours after an overdose.
DRUG INTERACTION
Simultaneous or sequential use of cisplatin with aminoglycoside antibiotics (gentamicin, kanamycin, streptomycin) or other potentially nephrotoxic (eg, amphotericin B) and ototoxic drugs (eg, loop diuretics such as furosemide, clopamide, ethacrynic acid) may potentiate its nephrotoxic and ototoxic effect.
It is known that cisplatin can disrupt the excretion via the kidneys of bleomycin and methotrexate (possibly due to cisplatin-induced nephrotoxic action) and increase the toxicity of these drugs.
In patients receiving cisplatin and anticonvulsants, the concentration of the latter in the serum can be reduced to subtherapeutic values. Cisplatin may cause an increase in the concentration of uric acid in the blood. Therefore, patients who simultaneously take medicines to treat gout, such as allopurinol, colchicine, probenecid or sulfinpyrazone, may need to adjust the dose of these drugs to control hyperuricemia and gout attacks.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Keep out of the reach of children at a temperature of no higher than 25 В° C. Shelf life - 18 months. Do not use after the expiration date printed on the package.
