Cisplatin (cis-diamindichloroplatinum) is an anticancer drug containing the heavy metal platinum.
Cisplatin has properties similar to those of bifunctional alkylating agents, which create inter- and intra-traction cross-links in DNA, thereby disrupting its function, leading to cell death, but the drug has no cyclic and phase specificity. It has immunosuppressive and radiosensitizing properties.
After a rapid IV infusion (15 minutes to 1 hour), the appearance of cisplatin in plasma and its peak concentration is determined immediately after administration. When administered by IV infusion over 6-24 h, the plasma concentration of the drug increases gradually during the infusion, reaching a maximum by the end of the infusion.
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 a three-hour infusion, 90% of platinum in plasma is bound to proteins. Cisplatin has ability to accumulate in body and be found in some tissues for six months after the last dose of medicine. Biotransformation of cisplatin occurs by rapid non-enzymatic transformation to form inactive metabolites. Only non-protein-bound cisplatin or its platinum-containing metabolites have cytotoxic effects.
The half-life of total platinum has a very wide individual variability and varies within 2-72 h in healthy people, and 1-240 h in severe renal insufficiency. Cisplatin is excreted mainly with urine. Cisplatin can be excreted from the systemic bloodstream by dialysis, but only during the first 3 h after administration.
Cisplatin, usually as part of combination chemotherapy regimens, is widely used in the treatment of the following solid tumors:
- germ cell tumors in 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;
- esophageal cancer.
1 ml contains:
Cisplatin 0.5 mg.
Hydrochloric acid or sodium hydroxide (to correct the pH level),
In a dark glass bottle 100 ml of solution.
There is 1 vial in the carton pack.
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 dosage selection should be guided by data from the literature.
Cisplatin is given intravenously or when indicated (intraperitoneal tumors) in the abdomen.
Cisplatin in monotherapy or in combination with other chemotherapies is administered at a dose of 50-100 mg/m2 as an IV infusion every 3-4 weeks or 15-20 mg/m2 by IV drip daily for 5 days every 3-4 weeks.
In order to stimulate diuresis (up to 100 ml/h) and to maximally reduce nephrotoxic effects of the drug, hydration is carried out. Before the
Cisplatin is administered by IV drops of up to 2 liters of fluid (0.9% sodium chloride solution or 5% dextrose solution). After the end of infusion an additional 400 ml of 0.9% sodium chloride solution or 5% dextrose solution is administered. Abundant fluid intake and maintenance of diuresis should be observed for 24 h. If intensive hydration to maintain adequate diuresis is insufficient, an osmotic diuretic (e.g. mannitol) can be given. Cisplastine is administered by IV drip at a rate not exceeding 1 mg/min. Prolonged infusions are given over 6-8-24 h, 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 1 mg/ml. Cisplatin lyophysilate should be dissolved in 10-25 ml of water for injection beforehand.
Do not use dextrose (glucose) solutions to dilute Cisplatin.
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.
Simultaneous or sequential use of cisplatin with aminoglycoside antibiotics (gentamicin, kanamycin, streptomycin) or with other potentially nephrotoxic drugs (e.g., amphotericin B) may potentiate its nephrotoxic and ototoxic effects.
“Loop” diuretics (furosemide, clopamide, etacrynic acid) may increase ototoxicity of cisplatin.
It is known that cisplatin can impair renal excretion of bleomycin and methotrexate (possibly due to cisplatin-induced nephrotoxicity) and increase toxicity of these drugs.
In patients receiving cisplatin and anticonvulsants, serum concentrations of the latter may decrease to subtherapeutic levels.
Cisplatin can cause elevated uric acid concentrations in the blood. Therefore, patients who simultaneously take gout medications such as allopurinol, colchicine, probenecid, or sulfinpyrazone may need to adjust the dosage of these drugs to control hyperuricemia and gout attacks.
The administration of Cisplatin should be supervised by a physician experienced in the use of antitumor drugs.
Men and women of childbearing age must use reliable contraception during Cisplatin treatment.
Patients on Cisplatin treatment should be periodically evaluated by a neurologist. Cisplatin therapy should be discontinued if there are clear symptoms of CNS toxicity.
An audiometry should be performed before initiating therapy, and repeat audiometry is indicated if there are symptoms of hearing impairment or clinical hearing loss. Dosage adjustment or discontinuation of therapy may be necessary if clinically significant hearing loss occurs.
With Cisplatin treatment, periodic blood counts, determination of white blood cells, platelets, hemoglobin, blood cells, renal and hepatic function tests, and serum electrolyte levels are necessary.
When using Cisplatin, all the usual instructions for the use of cytotoxic drugs must be followed. In case of contact of the drug with the eyes it should be immediately rinsed with plenty of water or 0.9% sodium chloride solution. In case of contact of the drug with skin the place of contact with the drug should be immediately rinsed with plenty of water. In case of inhalation of the drug or ingestion it is necessary to consult a doctor immediately.
- Individual intolerance to cisplatin or other compounds containing platinum;
- renal dysfunction (serum creatinine level greater than 115 μmol/L);
- inhibition of medullary hematopoiesis;
- heart failure;
- pregnancy and lactation;
- generalized infections.
Urinary system disorders: nephrotoxicity (is cumulative in nature and is a major dose-limiting toxic factor 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 and/or decreased creatinine clearance. Renal failure is usually mild to moderate and reversible at normal doses of Cisplatin.
In 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 by the use of 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. Slight and transient elevations of serum levels of AST and ALT may be noted occasionally.
With the hematopoietic system: often – myelosuppression, (in most cases it is mild to moderate and reversible with normal doses). The lowest levels of leukocytes and platelets are usually detected after about 2 weeks; their initial level in most patients is restored within 4 weeks. Anemia may also occur.
Hearing system: unilateral or bilateral tinnitus, with or without hearing loss, occurs in approximately 10% of patients; 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 have been reports of toxic effects 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. Lhermitte syndrome (spinal column myelopathy and autonomic neuropathy) has been reported in the literature. Treatment should be discontinued at the first appearance of these symptoms.
The immune system: sometimes allergic reactions have been noted, manifested as redness and swelling of the face, wheezing in the lungs, tachycardia and BP decrease. These reactions may occur within a few minutes after the start of cisplatin administration. In rare cases, urticaria and a patchy-papular skin rash may occur.
Visual system disorders: in rare cases optic neuritis, optic disc edema, cortical blindness have been observed. There may also be changes in color perception, especially 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.
Electrolyte balance disorders: hypomagnesemia, hypocalcemia and hypokalemia. Hypomagnesemia and/or hypocalcemia may manifest clinically with increased muscle sensitivity or cramps, tremor, carpopedal spasm (cramps in the hands and feet) and/or tetany. Hyponatremia due to inadequate antidiuretic hormone production syndrome is possible.
Local reactions: if the drug gets under the skin, phlebitis, cellulitis and skin necrosis may develop.
Other: disorders of the cardiovascular system (coronary heart disease, congestive heart failure, arrhythmias, orthostatic hypotension, thrombotic microangiopathy, etc.), hyperuricemia, minor alopecia, myalgia, fever and gum line platinum. Cases of impaired spermatogenesis and azoospermia have been reported.
The main expected complications of overdose are renal and hepatic dysfunction, visual (including retinal detachment) and hearing (deafness) disorders, severe myelosuppression, uncontrollable vomiting and/or severe neuritis. In case of overdose, death is possible.
The antidote to cisplatin is unknown. Treatment is symptomatic. Partial effect can be achieved with hemodialysis performed within the first three hours after overdose.
|Conditions of storage|
Store at a temperature not exceeding 25°C in a place protected from light and out of the reach of children.
Pharmahemi B.V., The Netherlands
concentrate for preparation of infusion solution
Buy Cisplatin-Teva, 0.5 mg/ml 100 ml with delivery to USA, UK, Europe and over 120 other countries.