- September 10, 2020
- Other drugs
- Ulyana Romanova
The drug "Cisplatin", the instructions for use of which will be studied in this article, is a cytotoxic drug. This is an inorganic substance that is a complex ammonium chloride of divalent platinum.
What conditions is this drug prescribed to treat? What is its effect? Are there any contraindications? You will find answers to these and many other questions in this article.
Pharmacodynamics and pharmacokinetics
Pharmacodynamics
Cisplatin is an antitumor agent , a platinum derivative. The mechanism of action is explained by the ability to penetrate cells, bind to cell DNA, forming cross-links that change the structure of DNA and disrupt its functioning.
Platinum cis-complexes form chelate compounds with nucleic acid molecules, forming stable bonds in the strands of the DNA helix. As a result, the synthesis of nucleic acids is suppressed and the cell dies. Protein and RNA synthesis is also suppressed, but to a lesser extent.
The antitumor effect also contributes to the immunosuppressive effect .
Pharmacokinetics
After intravenous infusion (rapid from 15 minutes to 1 hour), Cisplatin appears in the blood immediately in maximum concentration. With prolonged infusion (from 6 to 18 hours), the concentration increases gradually and reaches a maximum by the end of the administration.
The highest concentrations of the drug are found in the prostate gland, kidneys and liver. Only Cisplatin, which is not bound to proteins, has a cytotoxic effect. 2 hours after a 3-hour infusion, 90% of the platinum is in a bound state. Platinum accumulates during repeated courses of treatment, and it is detected in tissues within 6 months. after the last dose.
The half-life is 2-72 hours and up to 240 hours in renal failure . Most of the drug is excreted by the kidneys in the same form after 1 hour. Excretion through the digestive tract is negligible. With daily use there is a danger of accumulation of free platinum in the blood.
Overdose
The answer to the question of how Cisplatin is tolerated was given above. This is a serious drug, so there will be consequences from its use. But treatment carried out under the supervision of a doctor will do much more good than harm.
Can there be an overdose? Yes. Its main symptoms are:
- Continuous vomiting.
- Problems with vision (the retina may even detach).
- Hearing impairment.
- Myelosuppression.
- Severe neuritis.
- Severe dysfunction of the liver and kidneys.
If help is not provided on time, death may occur. Unfortunately, the antidote is unknown. Treatment is symptomatic; a partially positive result can be achieved with hemodialysis. The main thing is to start it within the first three hours after poisoning.
Indications for use
- germ cell tumors of women and men;
- and testicular cancer ;
- small cell and non-small cell lung cancer ;
- bladder cancer;
- squamous cell carcinoma of the head and neck ;
- cervical cancer;
- melanoma;
- osteosarcoma;
- neuroblastoma;
- lymphoma;
- esophageal carcinoma.
Side effects of Cisplatin
- nausea, vomiting, anorexia, stomatitis ;
- leukopenia , thrombocytopenia , anemia ;
- convulsions, neuropathies, ototoxicity, neuritis , color perception disorders ;
- hypocalcemia , hyperuricemia, hypomagnesemia;
- amenorrhea and azoospermia ;
- tachycardia , decreased blood pressure;
- rash, urticaria, angioedema .
Side effects such as ototoxicity and nephrotoxicity develop when using high doses. Renal damage is cumulative and is often the main factor that limits the dose of the drug. It is detected in the second week of treatment and is slightly pronounced at normal doses.
Instructions for use of Cisplatin (Method and dosage)
The dose is set individually. Before starting treatment, the blood picture, kidney and liver function, water-electrolyte metabolism, and uric acid levels are monitored.
IV, infusion over 6–8 hours. Long-term infusions are carried out provided that there is good diuresis during the administration of the drug. For certain diseases, the drug is administered intrapleurally, intraarterially, intraperitoneally.
The drug is dissolved (10 mg per 10 ml of water for injection), adjusted to 1 liter with a 5% glucose solution. A dose of 15-20 mg/m2 is administered every day for 5 days, 30 mg/m2 every day for 3 days, or 100-150 mg/m2 every 3 weeks. Treatment is carried out in the form of monotherapy or combination therapy with other cytostatics .
To prevent nausea, Ondansetron and Metoclopramide . The dose is reduced if bone marrow function is suppressed. Treatment is continued after blood tests normalize.
The instructions for use of Cisplatin contain warnings that before treatment it is necessary to hydrate to reduce the nephrotoxic effect - instill 2 liters of liquid 12 hours before taking the dose. Hydration is carried out against the background of the administration of an osmotic diuretic ( Mannitol ).
If the drug comes into contact with the skin, skin reactions occur. It is necessary to use gloves, a protective gown, a mask, and protect your eyes. In case of accidental contact with skin, wash off immediately with water and soap.
How is the solution prepared?
This question also needs to be answered, since we are talking about the use of Cisplatin for cancer. This medicine is usually diluted in a 0.9 percent sodium chloride solution. It requires about 1-2 liters.
Under no circumstances should dextrose solution be used. You should not use needles or any other equipment that contains aluminum to administer medication. Because this substance reacts with Cisplatin, as a result of which it is inactivated. A precipitate also forms, which is also unacceptable.
The solution must be administered immediately after it is prepared. It should not be mixed with any other liquids or medications. And the infusion is completed within 24 hours after preparing the medicine.
Interaction
Cisplatin is used in combination therapy with Vinblastine , bleomycin , Cyclophosphamide , Doxorubicin , Fluorouracil , Methotrexate .
The risk of nephropathy appears when used simultaneously with uricosuric drugs . Do not prescribe together with aminoglycosides , loop diuretics, cephalosporins, which enhance ototoxic, neurotoxic and nephrotoxic effects.
Use with antihistamines , anthelmintics (phenothiazines), neuroleptics (thioxanthenes) masks the symptoms of Cisplatin ototoxicity. Mannitol reduces its excretion in urine.
special instructions
The administration of Cisplatin should be carried out 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 treatment with Cisplatin.
Patients treated with Cisplatin should be periodically examined by a neurologist. If there are obvious symptoms of CNS toxicity, Cisplatin therapy should be discontinued.
Before starting therapy, audiometry should be performed, and in cases where symptoms of damage to the hearing organ appear or clinical hearing impairment is detected, repeated audiometry is indicated. For clinically significant hearing impairment, dosage adjustment or discontinuation of therapy may be required.
During treatment with Cisplatin, periodic blood tests are required, determining the content of leukocytes, platelets, hemoglobin, blood cells, renal and liver function tests, as well as the level of electrolytes in the blood serum.
When using Cisplatin, all usual instructions for the use of cytotoxic drugs must be followed.
If the drug gets into your eyes, rinse them immediately with plenty of water or 0.9% sodium chloride solution. If the drug comes into contact with the skin, immediately wash the area of contact with the drug with plenty of water. If the drug is inhaled or gets into your mouth, consult a doctor immediately.
Analogs
Level 4 ATC code matches:
Oxaliplatin
Carboplatin
Blastolem , Displanor , Kemoplat , Oncoplatin , Platidiam , Platimit , Platin , Platinum lyophilized for injection , Platinol , Cisanplat .
Reviews of Cisplatin
Reviews about Cisplatin on forums indicate that everyone’s tolerance to the drug is different. It depends on age and initial state of health.
Most often there are reviews from patients who used combinations of anticancer drugs. Among the side effects, vomiting was noted, and therefore the patients were prescribed Ondansetron , Zofran . To reduce hepatotoxicity - Heptral .
- “... I received Gemzar + Cisplatin according to the 1st, 8th and 21st day regimen. I took it very hard”;
- “... I took Cisplatin and Rinotecan, it was a bit heavy, I vomited, I didn’t eat anything”;
- “... I believe that Carboplatin is better tolerated than Cisplatin.”
Cisplatin today remains the most active in the treatment of ovarian tumors , and its combination with Taxol chemotherapy regimen for this disease.
If we compare the spectrum of action of Cisplatin and Paraplatin , then it is the same, but the latter has better tolerability - it does not have neuro- and ototoxicity. However, it inhibits granulocyte and platelet hematopoiesis to a greater extent.
There are clinical situations when Cisplatin is replaced with Paraplatin: serious renal dysfunction, signs of neurotoxicity, weakened patients, uncontrollable vomiting not eliminated by antiemetics .
Contraindications
As you can already understand, Cisplatin is a serious medicine. It is only available by prescription. There are a number of contraindications:
- Inhibition of hematopoiesis.
- Hyperuricemia.
- Hypersensitivity to the active substance of the drug.
- Kidney problems and dysfunction.
- Hearing problems.
- Polyneuritis.
- Nephrourolithiasis.
There are also conditions in which the drug is prescribed with caution. They can be identified in the following list:
- Acute infectious diseases. It doesn’t matter what their etiology is - bacterial, fungal or viral.
- Hyperuricemia, which manifests itself as urate nephrolithiasis or gout.
- Polyneuritis.
- Problems with bone marrow hematopoiesis.
- Polynephrourolithiasis.
- Injections with live antiviral vaccines.
However, under no circumstances, even in the smallest dosage, should Cisplatin be taken by pregnant and lactating women.
Cisplatin price, where to buy
You can buy it in many pharmacies in Moscow. The release form and price differ. Cisplatin 100 mg in a 100 ml bottle (TEBA, Pharmachemie) costs 1089 – 1109 rubles, 1 mg/ml 100 ml in a bottle 867 – 1109 rubles.
- Online pharmacies in UkraineUkraine
Pharmacy24
- Cisplatin Ebewe 100 mg/ml N1 concentrate for solution for infusion EBEVE Pharma Ges.m.b.H.Nfg.KG, Austria
1064 UAH.order - Cisplatin Accord 1 mg/ml 100 ml No. 1 concentrate Accord Healthcare Limited, Great Britain
800 UAH order
- Cisplatin Ebewe 100 ml 50 mg N1 concentrate EBEVE Pharma Ges.m.b.H.Nfg.KG, Austria
512 UAH. order
- Cisplatin Accord 1mg/ml 50ml No. 1 concentrate Accord Healthcare Limited, Great Britain
400 UAH order
