Cisplatin 10mg Bidiphar cancer treatment (20ml)

Do not consider cisplatin as the first choice to treat bladder cancer, head and neck cancer, but only in combination with surgical or radiation methods to treat these cancer in the late stages or recurrence.

Pharmacology

Pharmacological group: anti -cancer chemotherapy, Platin compound

ATC code: L01xa01

cisplatin is a anti-cancer drug containing platinum (inorganic containing heavy metals [CIS-DIAMinedichlorididoplatinum (II)]), has a toxic effect on cells, anti-tumor and has the same characteristics as alkylation. The drug is often used in many treatment regimens due to relatively less toxic hematology. Cisplatin forms cross and between DNA fibers, which should change the structure of DNA and DNA synthesis inhibitors.

Although the most important mechanism is DNA synthesis inhibitors, other mechanisms can also contribute to increased anti -cancer activity of cisplatin, including increased tumor immunity. Cisplatin tumor destruction properties are compared to Alkyl agents.

Cisplatin's cytotoxic effects are associated with all DNA bases, priority in the N-7 position of Guanin and Adenosin.

The anti -drug cell mechanism contains platinums that have not been clarified, but anti -drug cells may be related to cells reducing the absorption of drugs or due to DNA repair and may be associated with increased sulfhydryl complex concentration including glutathion or metallonein in cells. Glutathion has a major role in protecting cells against the effects of some toxins including some anti -cancer drugs.

Dynamic pharmacokinetics

Pharmacokinetics change a lot, depending on the dosage, speed of transmission, supplementary water through intravenously and simultaneously used with diuretics. The relationship between treatment or toxicity with cisplatin or platinum concentration in plasma has not been clearly defined. However, in vitro research shows that only cisplatin is not attached to protein or platinum -containing products that are toxic cells.

absorption:

After rapid intravenous injection for 1-5 minutes or fast intravenous infusion for 15 minutes, the concentration of drugs and plasand in plasma reaches maximum. After rapid intravenous injection of a dose of 50 mg/m2 Cisplatin for 3-5 minutes for patients with normal kidney function, the plasma peak concentration of intact cisplatin is 2.3 micrograms/ml, of the whole platin is 4.7 micrograms/ml and of non -attached plats on protein is 2.7 micrograms/ml. When cisplatin intravenously within 6 or 24 hours, plasma concentration of the whole platinity increases gradually while transmitting, and reaching the top after transmission. After intravenous infusion for 6 hours 1 dose 100 mg/m2 for people with normal renal function, the peak concentration of plasma of the whole platinum is 2.5 - 5.3 micrograms/ml and the platinum is not attached to the protein of 0.22 - 0.73 micrograms/ml.

Intravenous infusion simultaneously cisplatin and manitol increase the plasma peak concentration of the platinum not attached to the protein, but there are also studies that there is no effect on the plasma concentrations of intact cisplatin, total platinum or platinum not attached to protein.

Distribution:

After adding cisplatin by intravenously, platinums are widely distributed into fluid and body tissue with the highest concentration: kidney, liver and prostate; Lower concentration: bladder muscles, testicles, pancreas and spleen; The platin is also distributed into the colon and the colon, the adrenal gland, the heart, the lungs, lymph nodes, the thyroid gland, the gallbladder, the thymus, the brain, the cerebellum, the ovaries and the uterus. The platinum accumulates in tissue and up to 6 months after the injection is still detected. The platinum distributes at least into leukemia and red blood cells. Platinum distribution volume in adults after intravenous injection: 20 - 80 liters. The platine is quickly distributed into pleural fluid, peritoneal after intravenous infusion. Cisplatin into breast milk and have little data that the drug through the placenta. Platinum from cisplatin, quickly attach strongly to the protein of the tissues and plasma. This cohesion is not reversed, and increases over time. Under 2 - 10% of the blood platinum is not attached to proteins a few hours after cisplatin intravenous injection.

Era:

After injection or intravenous cisplatin, plasma concentrations of intact cisplatin, total platinum platinum and platinum not attached to protein decreased by 1 phase and 2 corresponding phases. In people with normal kidney function, after getting or transmitting quickly cisplatin, the exhaust time of intact cisplatin: about 20 minutes; Complete platinum: 8.1 - 49 minutes in the first phase and 30.5 - 107 hours in the last phase; The platin is not attached to the protein: 2.7 - 30 minutes in the first phase and 32 - 53.5 minutes in the last phase. In children with normal kidney function, the duration of the serum waste in the whole platinated platinum: about 25 minutes in the first phase and 44 hours in the last phase; Platinum is not attached to protein: about 1.3 hours. Cisplatin metabolism has not been fully known. So far there has been no evidence of drugs that have been metabolized through enzymes. Intact cisplatin and platinum products are excreted mainly in urine; The platinum eliminates through the stool is negligible. Cisplatin and products containing platinums undergoing intestinal circulation - liver.

After injection or rapid intravenous cisplatin in humans with normal renal function, about 15-50% of the dose excreted into the urine within 24 - 48 hours, most of them in the first 4-6 hours. In people with renal failure, cisplatin elimination and platinum -containing products have not been fully evaluated, maybe the plasma concentration of the platinum does not have an increase in protein.

cisplatin and/or platinum products are removed very little by blood decentralization.

Cisplatin concentrated solution 10mg/20ml should be diluted in 1-2 liters of the solution mentioned above.

Only use when the solution is transparent, colorless and there is no visible sub -stool.

Should be infused for 6 - 8 hours.

From 2 to 12 hours before use until at least 6 hours after using cisplatin must be fully watered for patients to ensure good urinary tract and minimize the toxicity on the kidneys in and after using Cisplatin.

Advanted intravenously 1 - 2 liters of fluid for 8 - 12 hours before taking the drug. In adults, unless there is contraindication, usually only a single infusion or a manitol and/or Furosemid at the original speed enough to maintain 150 - 400 ml/hour cards while giving cisplatin, and at least 4-6 hours after cisplatin. Then, maintain the urinary tract ≥ 100 - 200 ml/hour, in the next 18 - 24 hours or until the vomiting is stopped and can be taken.

In 24 hours after cisplatin transmission, patients need to drink large amounts of liquid to ensure the production of urine.

Some special notes on drug treatment before and after use

Like other cytotoxic substances, users need to be cautious when using, need to be equipped with gloves, protective robes, protective glasses, masks.

It is necessary to follow the instructions on the treatment of cytotoxic toxic substances specified in each place of drug use.

Need to prepare cisplatin in the cabinet, in a private room.

Avoid direct contact with the skin and mucous membranes.

Health staff should not contact and handle cisplatin while pregnant.

In case of contact with the skin: Wash a lot with water and soap. Use ointment to soothe the feeling of temporary burns. Note: For some people sensitive to the platinum, the skin reaction may be encountered.

Must use a syringe with a tight pit - a tone to fit, the needle gut must be wide to avoid air bubbles when mixing the drug. Air bubbles also decrease if you use an additional pine needle when mixing the drug.

The waste products or items left after using the drug preparation must be processed according to the internal instructions at the place of use (should be added in plastic bags 2 times and burned at 1100 ° C).

In case of leaked drugs: If the drug is leaked out, it is necessary to control the infected area. Users should wear 2 times gloves, masks, protective robes, protective glasses. Limit the infection area by covering a absorbent towel or adsorbent particles. It can also be processed with 5%sodium hypoclorite. Collect all drugs and debris into a plastic, closed, external bag that is "very toxic rubbish for cells, which should be burned at 1100 ° C". The infected area after treatment, need to wash with lots of water.

In case of overflow, all exposure to cisplatin must be treated according to internal instructions for cytotoxic drugs at the place where the drug is used.

Dosage

Cisplatin dose must be based on kidney clinical response, hematology, hearing and drug tolerance to achieve maximum results with minimum side effects.

Doctors must carefully refer to the published regimens of cisplatin and other chemotherapy drugs, methods and sequences for the drug. With a common dose, a cisplatin course must not be used more than 1 time 3-4 weeks apart. Do not repeat the cisplatin process if the kidney, hematological and hearing function has not returned to an acceptable limit and is always ready to deal with anaphylactic reactions. Cisplatin is a high risk of vomiting, so anti -vomiting drugs

Testicular cancer:

The usual dose in chemotherapy (as with Bleomycin and Etoposid): Cisplatin 20 mg/m2 of the body area, daily intravenous infusion for 5 days, 3 weeks/1 course for 3 or 4 procedures. Usually only 3 procedures.

Ovarian cancer (late stage):

When combined with Paclitaxel, the dose of Cisplatin 75 mg/m2 of the body area, intravenously 1 time every 3 weeks.

When combined with cyclophosphamide, the usual dosage Cisplatin 50 - 100 mg/m2 of the body area, intravenous infusion 1 time every 3-4 weeks.

Information about the dose, usage of Paclitaxel and Cyclophosphamid, refer to the product information Paclitaxel and Cyclophosphamide.

If Cisplatin is used alone, taking a dose of 100 mg/m2 of the body area, an intravenous one -time infusion every 4 weeks. In addition, some specialized physicians recommend that the dose is 50 - 100 mg/m2 of the body area, intravenously every 3 weeks.

Bladder cancer (late stage):

Normal doses of cisplatin 50 - 70 mg/m2 of the body area, intravenously every 3-4 weeks, depending on the level of radiation therapy and/or chemotherapy first. For patients who have been strongly treated before. The initial dose recommends: 50 mg/m2 of the body area, intravenously every 4 weeks.

Cancer in the head and neck:

Cisplatin alone: ​​80 - 120 mg/m2 of the body area, intravenously every 3 weeks or 50 mg/m2 of the body area, intravenous infusion on the first and 8th day of every 4 weeks.

If used in combination, the normal dosage of cisplatin is 50 - 120 mg/m2 of the body area, intravenously, the number of times used depends on the used regimen.

Cervical cancer:

Invasive cervical cancer:

Renal failure: Contraindications.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.

What to do when overdose?

Symptoms:

Symptoms of overdose are included in the above unwanted effects in a more excessive way. The effectiveness of water and osmotic diuretics can help reduce toxicity, which should be done immediately after overdose.

In case of an overdose (≥ 200 mg/m2), it can lead to a direct impact on the respiratory center. This can cause life -threatening respiratory disorders and base basic balance disorders because of the brain barrier.

Cisplatin's acute overdose can cause kidney failure, liver failure, deafness, toxic eye (including retinal peeling), significant bone marrow inhibition, untreated nausea, vomiting and/or neuritis. Overdose can be fatal.

How to handle:

Although currently the specific antidote for cisplatin has not been identified when overdose, some Sulfhydryl (thiol) compounds (causing reducing) (such as glutathion, acetylcystein, Mesna) can be inactivated Cisplatin and act as chemical protection substances (as protective against toxicity to the kidney). However, the potential of the benefits of these drugs also needs to be determined. The benefits of many drugs, if any, is limited if given a few hours late after using cisplatin because most platinums can be attached to protein and in non -reactive form. Theoretically, dithiocarbamat drugs (such as Dithiocarb DDTC, Amifostin) may have more potential benefits, as these drugs have the ability to react with the platin even after attaching to the protein and can stimulate the elimination of a large amount of platinum through bile. The role of the above drugs should be further clarified.

When poisoning and overdose, often treated as symptoms. Bloody dysfunction is less eliminated platinum, even when done within the first 4 hours. Instead of plasma withdrawal can remove platinum attached to protein, thus improving poisoning.

If vomiting continuously, anti -vomiting drugs (Serotonin receptor resistant drugs 3, dexamethason and aprepitant). Hematopoietic drugs (such as sargramostim [GM-CSF]) may help in treating myelosuppression and hemolysis may be needed to manage kidney failure

In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

Be cautious when using

cisplatin is only used by a doctor who has experience in treatment with poison with cells.

Avoid aluminum tools in contact with cisplatin (intravenous transmission, needle, catheter, syringe).

It is necessary to prepare supportive care facilities to control anaphylactic reactions.

Do not mix the infusion solution with other drugs or additives.

Need to monitor and strictly manage the treatment and complications for appropriate diagnosis and treatment.

cisplatin has been shown to cause toxicity on the ear, kidneys and nerves. Toxicity caused by cisplatin can be amplified when used in combination with other drug products that are toxic to the organ and system.

Before, during and after treatment with cisplatin, it is necessary to identify and evaluate the indicators that meet the following organs:

These tests should be repeated every week during treatment with cisplatin.

Repeated treatment with cisplatin must be suspended until the normal value of the following indicators is evaluated:

Kidney toxicity:

cisplatin may cause severe kidney toxicity. The amount of urine output ≥ 100ml/hour will aim to minimize the kidney toxicity of cisplatin. This can be achieved by transmitting 2 liters of epidemic before using the drug and almost needed water after using cisplatin (recommended 2500ml/m2/24 hours).

If the water continued is not enough to maintain the amount of urine secretion, an osmotic diuretic can be prescribed (like mannitol). Hypergly uric acid and hyperllying blood albumin can affect kidney toxicity caused by cisplatin.

neuropathy:

Cases of severe neurological disease have been reported.

These neurological diseases may not be recovered and may manifest evidence of paresthesia, loss of reflexes, loss of self and vibration sensation. Loss of motor function has also been reported. The neurological test must be conducted regularly.

Special prudence for patients with peripheral neuropathy is not caused by cisplatin. Before each treatment, it is necessary to redefine the presence of peripheral neuropathy symptoms.Ear toxicity:

Toxicity on the ears has been observed in 31% of patients treated with single dose of Cisplatin 50mg/ m2, and is manifested as evidence of tinnitus and/ or loss of hearing at high frequency (4000 - 8000 Hz). Reduce the ability to hear the voice may occur. Ear toxicity effects can be more evident in children being treated with cisplatin. Hearing loss may be on one or both sides and tend to occur more often and worse with repeated doses. However, deafness after the starting dose of cisplatin is rarely reported. The toxicity on the ear can be increased when irradiated at the same time as the cranial and may be related to the plasma peak concentration of cisplatin. It is unclear whether cisplatin is capable of recovery. Careful monitoring should be monitored by hearing before the first process and before using cisplatin doses later. Vestibular toxicity has also been reported.

Allergic phenomenon:

As other platinum products, hypersensitivity reactions appear in most cases during the transmission process, and need to stop the appropriate translation and treatment of symptoms. Cross reactions are sometimes fatal, reported to all platinum compounds.

Anaphylactic reactions have been observed. These reactions can be controlled by antihistamines, adrenalin and/or glucocorticoids.

Liver function and blood formula:

Blood formula and liver function must be monitored regularly.

Cancer ability:

In humans, in rare cases, acute leukemia occurs simultaneously with the use of cisplatin, this is generally related to other leukemia causing agents. Cisplatin is a mutant factor in bacteria and causes chromosomal deviations in culture on animal cells. The possibility of cancer is possible but not yet proven. Cisplatin is a monitoring agent and embryo toxicity in mice.

Reaction at the injection site:

The reaction at the injection site may occur during the use of cisplatin. The ability to exit the circuit, recommend closely monitoring at the infusion position because of the possibility of leakage during use. Specific treatment for the exit reaction to this point is not known.

Be cautious when used for children:

Safety and efficiency in children have not been proven.

All children need to be assessed for hearing before starting treatment, before taking the next and annual doses after treatment.

Advanced test methods allow early detection of poor hearing ability in children, creating favorable conditions for early intervention to limit the potential adverse impact of hearing loss for children's cognitive development and social development.

Be cautious when used for the elderly:

Some research analysis shows that older people have shorter life, platelet reduction rate and getting worse and severe than young patients.

Elderly people have a higher rate of peripheral neuropathy than young patients. Other clinical experiences show that the elderly is prone to muscle atrophy, infection complications and higher kidney toxicity than younger patients.

Cisplatin is known for its effects on the kidneys and contraindicated in patients with renal failure. Therefore, it is necessary to be cautious when choosing the dose and should closely monitor the kidney function in the elderly patients.

Note and other recommendations:

The injection solution should be checked by the naked eye to see if there are strange and discolored objects before use or not, every time they come into contact with the solution and the packaging. Check the solution in the jar to see if there are strange things and check when transferring the drug from the vial to the syringe.

Pleeing: Be careful to avoid the occurrence of vascular escape and infusion position should be checked for signs of inflammation. If the vascular escape occurs, wash the infusion site with aseptic water and recommend the use of cold ice.

The effect of drugs on driving and operating machinery

has no complete research on the effects and impacts of drugs when driving and operating machinery.

However, cisplatin has unwanted effects on the central nervous system and senses. Therefore, the drug can cause light or medium impact on the ability to drive and operate machinery. Avoid driving and operating machinery when these effects appear (such as drowsiness or vomiting).

Using drugs for women during pregnancy and lactation

Pregnancy:

cisplatin can be toxic to the fetus when used for pregnant women.

cisplatin causes mutations in bacteria and creates chromosomal deviations in animal cells in tissue culture. Animal tests show the toxicity of the fetus and toxicity through the placenta. In mice, cisplatin causes teratogenic and toxic to the workpiece.

Do not use cisplatin during pregnancy, unless the doctor assesses the risk of each patient to clinically adjust and only use cisplatin when considering the benefits than the risk that the drug can cause.

If using this medication during pregnancy or if the patient is pregnant while taking the drug, the patient needs to be notified of potential risks to the fetus.

Breastfeeding period:

Cisplatin is excreted into breast milk. Because the drug is at high risk of damaging children, not breastfeeding when mothers use cisplatin.

Reproduction:

Patients need genetic advice when taking the drug. Because cisplatin treatment can cause non -recovery infertility in men, male patients need to be notified about this risk before starting treatment and need advice on sperm preservation.

During treatment with cisplatin and at least 6 months after treatment, appropriate contraceptive measures are needed to avoid pregnancy. Contraceptive should be performed in both men and women.

Drug interaction

Simultaneous use of bone marrow inhibitors or irradiation will increase the effect of bone marrow inhibition. The appearance of kidney toxicity caused by cisplatin can be enhanced by simultaneous use of anti -hypertension drugs containing Furosemid, Hydralazin, Diazoxid and Propranolol.

Kidney toxic substances

Concentrated use of kidney toxic drugs (such as cephalosporin, aminoglycosides, or amphotericin B or contrast substances) increases the toxicity of cisplatin on the kidneys.

During and after treatment with cisplatin, it is necessary to be cautious with the main exclusion of the kidneys (for example, cell pliers such as Bleomycin and Methotrexate because of reducing renal excretion). Cisplatin when combined with Bleomycin and Vinblastin can lead to Raynaud's syndrome.

IFOSFAMID's kidney toxicity may be larger when it is used with cisplatin or for patients who have been treated with cisplatin.

Hemorrhoids decreased in some cases after using cisplatin with BLEOMYCIN and ETOPOSID. Therefore, lithium value should be monitored.

may need to adjust the dose of Allopurinol, Colchicin, Probenecid or SulfinPyrazon if used with cisplatin because cisplatin increases serum uric acid levels.

In a test in advanced or metastatic cancer patients, Docetaxel in collaboration with cisplatin causes a worse neurological effect when taking alone at the equivalent dose.

Chelate complex artificial agents like penicillamin can reduce the effectiveness of cisplatin.

Concomitance Cisplatin and ciclosporin use, excessive immunosuppressive inhibition with the risk of lymph tissue hypernage should be considered.

toxins on the ears

Use simultaneously toxic substances (such as aminoglycosides, diuretics) will be toxic to the hearing function. Except for patients with cisplatin doses more than 60 mg/m2, and there is an excretion of urine less than 1,000 ml/24 hours, should not be tied with diuretic with diuretics due to the ability to poison the kidneys and toxicity on the ear.

iFosfamid may increase hearing loss due to cisplatin.

Live vaccines are weak

The yellow fever vaccine is completely contraindicated by increasing the risk of severe body reactions associated with death vaccines. With the risk of disease in general, the vaccine should not work if needed.

Oral anticoagulants

When using the oral anticoagulant simultaneously, check regularly Inr.

antihistamine, phenothiazine and other drugs

Concomitance cisplatin use with antihistamine drugs, bulizin, cyclizin, loxapin, meclozin, phenothiazin, thioxanthen or trimethobenzamide can cover the symptoms of ear toxicity (such as dizziness and tinnitus).

anti -epileptic drugs

Serum concentration of anti -epileptic drugs can be maintained below the treatment level during treatment with cisplatin. Cisplatin can reduce the absorption of phenytoin leading to reduced control of epilepsy when phenytoin is put into treatment. Start the treatment of epilepsy while using cisplatin completely contraindicated.

combination of pyroxidin and alteramine

In the random trial of the treatment of progressive ovarian cancer, the response time is adverse effects when pyroxidin is used in combination with alteramine (Hexamethylmelamin) and Cisplatin.

paclitaxel

Cisplatin treatment before Paclitaxel can reduce the clearance of Paclitaxel 33% and therefore can enhance neurotoxicity.