Gemcitabin medicine 1000mg/100ml eBewe to treat bladder cancer, pancreatic cancer

ATC code: L01BC05

Cellular activity in cell culture:

Gemcitabin has significant cytotoxic effect against many types of tumor cells cultured in mice and humans. The drug has a specific phase effect, such as gemcitabin mainly killing cells in the DNA synthesis (phase S) and, in some conditions and blocking the progression of cells at the boundary of the two -phase boundary G1/s. In vitro, cytotoxic effect of gemcitabin depending on both concentration and time.

Anti -tumor effects in preclinical models:

In animal tumor -causing models, the anti -tumor effect of gemcitabin depends on the usage. Using gemcitabin daily shows high death rates in animals, but has a minimum anti -tumor activity. However, if you use gemcitabin every 3 or 4 days, you can use the drug in the dosage that does not cause animal death but has a widespread anti -tumor activity for mice tumors.

Dynamic pharmacokinetics

Gemcitabin pharmacokinetics are observed in 353 patients in 7 research works, including 121 female and 232 men, 29 - 79. Among these patients, about 45% of lung cancer is not small cells and 35% are diagnosed with organs. The following parameters have been achieved in doses of 500 - 2592 mg/m2 and transmitted in the period of 0.4 - 1.2 hours.

Peak concentration in plasma (reaching about 5 minutes after the transmission) is 3.2 - 45.5 micrograms/ml. The plasma concentration of the mother after taking the dose of 1000mg/m2/30 minutes is> 5 micrograms/ml for about 30 minutes and at the end of the transmission, and> 0.4 micrograms/ml in the next hour.

Distribution:

The distribution of the main compartment is 12.4 liters/m2 for women and 17.5 liters/m2 for men (the change between individuals is 91.9%). The distribution of the peripheral interval is 47.4 liters/m2. The distribution of the peripheral interval does not change according to gender.

The cohesion on plasma proteins is not significant.

The sale time is 42 - 94 minutes depending on the age and gender. With the proposed drug schedule, Gemcitabin's elimination is almost completely within 5 - 11 hours after the start of transmission. Gemcitabin does not accumulate if used once a week.

Metabolism

Gemcitabin metabolizes rapidly through the catalyst of the cytidin enzyme - Desaminase in the liver, kidneys, blood and other tissues. Gemcitabin's intracellular metabolism will produce gemcitabin Mono - Di and Triphosphate metabolites (DFDCMP, DFDCDP and DFDCTP), among which CDFDCDP and DFDCTP are considered active. The intracellular metabolites are not found in plasma and urine. The first metabolites, 2 desoxy- 2'-2- difluorouridine (DFDU) are not active and found in plasma and urine.

Elimination

The body clearance is about 29.2 liters/hour/m2 - 92.2 liters/m2 depending on the gender and age (the difference between individuals is 52.5%). Lighter in women's clearance in men is about 25%. Despite being quickly excreted, the clearance for both men and women may decrease with age. With the recommended gemcitabin dose of 1000mg/m2 for 30 minutes, even if the clearance is low for both women and men, there is no need to reduce the dose of gemcitabin.

Disage through urine:

Rid of the kidney clearance is 2 - 7 liters/hour/m2

During a week after the transmission has found 92% - 98% of the gemcitabin dose was used, 99% in urine, mainly in the form of DFDU ​​and 1% of the dose is discharged through feces.

DFDU's dynamics

Peak concentration in plasma (reaching about 3-15 minutes after 30 minutes, 1000mg/m2) is 28 - 52 micrograms/ml.

The bottom concentration after 1 week: 0.07 - 1.12 micrograms/ml, without accumulation. The concentration of plasma in three phases compared to the time line, the semi -waste time of the ending phase is 65 hours (33 - 84 hours).

Create dfdu from mother substance: 91% - 98%.

The average distribution volume in the main compartment: 18 liters/m2 (11-22 liters/m2).

The average distribution volume at stable state (VSS): 150 liters/m2 (96 - 228 liters/m2).

Distribution into tissue: wide.

Average clearance: 2.5 liters/hour/m2 (1 - 4 liters/hour/m2).

Disage through urine: All.

Combining Gemcitabin + Paclitaxel: does not affect the pharmacokinetics of Gemcitabin or Paclitaxel.

Combining Gemcitabin + Carboplatin: Such a combination does not change the pharmacobi of Paclitaxel

kidney failure

Mild and medium renal failure (GFR glomerular filtration speed is 30 - 80ml/minute) does not significantly affect the pharmacokinetics of Gemcitabin.

gemcitabin is only prescribed by an in -depth physician for anti -cancer drug use.

Bladder cancer

Medicine coordination:

The recommended dose gemcitabine is 1000 mg/m2, transmitted for 30 minutes. Take the dose on 1-8 and 15 days of each 28 -day cycle, coordinated with cisplatin. The recommended dose of cisplatin is 70 mg/m2 on day 1 after gemcitabin or on the 2nd day of each 28 -day cycle. That 4 -week cycle will be repeated. The decrease in the dose for each cycle or in each cycle is applied based on the level of toxic to the patient.

Pancreatic cancer:

The gemcitabine recommended dose is 1000 mg/m2, intravenously for 30 minutes, this dose is repeated once a week within 7 weeks, followed by 1 week off. Use this dose once a week for 3 weeks, then stop 1 week. Just like that repeat this 4 week cycle. The dose can be reduced for each cycle or in each cycle based on the level of toxic to the patient.

Non -small cell lung cancer

Caution when using

extending the transmission time and increasing the dose frequency will increase toxicity.

Hematology toxicity:

gemcitabin may reduce the bone marrow function manifested by leukopenia, platelets and anemia.

Patients with gemcitabin should be monitored before each dose of quantity, platelets, leukocytes and granulocytes. Every time you detect bone marrow failure, should consider stopping medication or changing treatment. However, marrow failure in a short time and often do not need to reduce the dose and rarely stop treatment.

After stopping gemcitabin, the amount of peripheral blood may continue to be reduced. For patients with bone marrow failure, it is necessary to start treatment carefully. Along with other cell pliers, the risk of bone marrow inhibition must be considered when using gemcitabin along with other chemotherapy drugs.

Hepatic and renal failure:

Be careful when taking gemcitabin for patients with liver or kidney function failure because there is no enough information on clinical research to recommend clear doses for these subjects. Using gemcitabin for patients with liver metastases or a history of hepatitis along with alcoholism or cirrhosis can drag with the play of the available liver failure. It is necessary to conduct regular assessments of liver and kidney function (including virus evaluation).

Coordinate with radiation:

Coordinate with radiation (simultaneous use or ≤ 7 days): toxicity occurred.

Living vaccine: It is not recommended for a fever -fever vaccine and other toxic reduced vaccines for patients to use gemcitabin.

Cardiovascular:

Due to the risk of heart and/or blood vessels when using gemcitabin, it is necessary to be especially cautious when used for patients with a history of cardiovascular phenomena.

The rear brain damage syndrome is capable of recovering (PresS):

There have been reports on cases of rear brain damage syndrome that is recovered (PresS) with serious risks that have been reported in patients using lone gemcitabine or used with other chemotherapy drugs. There have been reports on acute hypertension and convulsions in patients with presents using gemcitabin, other symptoms such as headaches, coma, confusion and blindness can also occur. It is best to use magnetic resonance imaging (MRI) to diagnose. Typically the prescription syndrome can recover if appropriate support measures. If during the treatment process, the Pres presity syndrome should stop and do not repeat the treatment with gemcitabine and supplement support measures, including blood pressure control and anti -epileptic treatment.

capillary leak syndrome:

There have been reports on capillary leakage syndrome in patients using single therapy gemcitabin or in combination with other chemotherapy drugs. This syndrome can be treated if detected early and appropriately controlled, but there are also reports on deaths. This is related to the increase in the permeability of the capillary wall in the liquid process and the protein from the endothelium leaked into the interstitial. Clinical symptoms include systemic edema, weight gain, hypotension, serious hypotension, acute renal failure and pulmonary edema. Gemcitabine should be stopped and taken supportive measures if capillary leak syndrome progresses during treatment. Capillary leaky syndrome may appear in later and theoretical cycles, it is related to respiratory failure syndrome in adults.

Lung:

When using gemcitabin has encountered lung phenomena, sometimes serious (such as pulmonary edema, interstitial pneumonia or severe respiratory failure syndrome in adults (ARDS). It is unclear the cause of these effects.

Kidney:

In gemcitabin users, rare clinical detections of hemolyticemia syndrome (HUS). Gemcitabin should be discontinued when they experience the first signs of evidence of microchemical hemolysis, such as rapid hemoglobin, accompanied by platelets, increased bilirubin, creatinine in serum, increased blood urea or LDH. Kidney disease may not recover when stopping medication and may need a separation.

Reproduction:

Research on reproduction shows that gemcitabin causes sperm deficiency in male mice. Therefore, men who use gemcitabin must be warned that they do not have children during medication and all 6 months after treatment and need to be advised to store sperm before the beginning of treatment may be likely to be infertile due to gemcitabin.

Gemcitabin "ebewe" 200 mg contains 21.49 mg (0.93 mmol) sodium, gemcitabin "eBewe" 1000 mg contains 107.47 mg (4.67 mmol) sodium in a vial. Therefore, it is necessary to consider when used in patients with salt diet.

Using drugs for women during pregnancy and lactation

pregnancy:

There is no adequate data on the use of gemcitabin in pregnant people. Animal studies show that drugs are toxic on reproduction.

Based on the results on animals and the mechanism of the action of gemcitabin, it is not advisable to use this medication during pregnancy, unless it is really necessary.

Women need to be told not to be pregnant during the use of gemcitabin and need to report immediately to the doctor when pregnant, although in precaution.

Breastfeeding period:

It is unclear the excretion of the mother's milk through the mother's milk and does not exclude the unwanted effect of this drug to the breastfed child. Must stop breastfeeding during mothers using gemcitabin.

Reproduction:

In reproductive studies, gemcitabin found that reducing sperm creation in male mice. Therefore, men who use gemcitabin must not have children during use and all 6 months after using this drug and are recommended to store sperm before treatment because they can be infertile due to gemcitabin.

affects the ability to drive and operate machinery

have not conducted research on the effect of this drug on the ability to drive and operate the machine. However, gemcitabin causes mild to medium drowsiness, especially when drinking with alcohol.

Patients need to be cautious when driving and operating the machine until it is clearly not sleepy.

Drug interaction

has not conducted specialized interactive studies.

Radiotherapy:

When combined with radiation (using or ≤ 7 days): There are many treatments depending on many different factors, including gemcitabin dose, frequency of use, gemcitabine, ray dose, radiation techniques, target tissue, and volume of target tissue, preclinical and clinical research show that Gemcitabin increases radiation sensitivity.

In a single test, when using gemcitabin at a dose of 1000 mg/m2 in the same 6 consecutive weeks with the chest treatment for patients with non -cell lung cancer patients with small cells, have a clear toxicity in the form of serious mucous inflammation, life -threatening, especially esophagitis and pneumonia, especially in patients with large radiation. The next studies show that the lower gemcitabine dose can be used with a ray projection to predict toxicity, as in the study of non -small cell phase II, using 66 gy as the chest ray dose in combination with Gemcitabin (600 mg/m2, 4 times) and Cisplatin (80 mg/m2, twice), conducted for 6 weeks. Currently, the optimal mode has not been determined for all types of tumors to use safe gemcitabin along with radiation doses.

When not coordinated (use> 7 days): Analysis of data does not show an increase in toxicity when using gemcitabin more than 7 days before or after the ray projection. The data shows that it is possible to start using gemcitabin after the acute effects of radiation are available or at least 1 week after the ray.

The complications caused by rays are encountered in the target tissue (e.g. esophagitis, colitis and pneumonia) when monomers and treatment in combination with gemcitabine.

Other interactions:

It is not recommended to use yellow fever vaccines and other toxic reduced vaccines due to the risk of systemic diseases, which can be fatal, especially in immunodeficiency patients.