Gemzar 200mg bottle №1

Mechanism of action

Antitumor drug, antimetabolite group of pyrimidine analogs. The drug shows cyclospecificity, acting on cells in phases S and G₁/ S.

Gemcitabine is metabolized within the cell by the action of nucleoside kinase to form active diphosphate and triphosphate nucleosides. Diphosphate nucleosides inhibit ribonucleotide reductase, which acts as the sole catalyst of the reactions leading to the formation of deoxynucleoside triphosphates necessary for DNA synthesis. Triphosphate nucleosides actively compete with deoxycytidine triphosphate for incorporation into DNA and RNA molecules. After the intracellular metabolites of gemcitabine are inserted into the DNA chain, another additional nucleotide is added to its growing strands, which leads to complete inhibition of further DNA synthesis and programmed cell death, known as apoptosis.

Pharmacokinetics

Distribution

Plasma protein binding is negligible.

Removal

T_1/2 ranges from 32 to 94 min. Gemcitabine is rapidly excreted in the urine mainly as an inactive metabolite 2'-deoxy-2 ', 2'-difluoro-uridine. Less than 10% of the dose injected in / in, found in the urine unchanged.

System clearance ranges from 30 to 90 l / h / m².

Pharmacokinetics in special clinical situations

Analysis of pharmacokinetic studies with single and multiple administration of the drug shows that V_d largely dependent on gender.

Systemic clearance depends on gender and age.

Mild or moderate renal failure (glomerular filtration rate of 30 to 80 ml / min) does not have a significant effect on gemcitabine pharmacokinetics.

Indications for use of the drug

- non-small cell lung cancer;

- mammary cancer;

- bladder cancer;

- ovarian cancer;

- pancreas cancer;

- cervical cancer.

Gemcitabine in monotherapy or in combination with other anticancer agents is also active in locally advanced small cell lung cancer, locally advanced refractory testicular cancer and biliary tract cancer.

Dosage and administration

Gemcitabine is introduced into / into the drip for 30 minutes.

At non-small cell lung cancer (locally advanced or metastatic) in the form of monotherapy recommended dose of the drug is 1000 mg / m² at 1, 8 and 15 days of each 28-day cycle. When used as part of combination therapy, the recommended dose of the drug is 1250 mg / m² on the 1st and the 8th day of each 21-day cycle or 1000 mg / m² at 1, 8 and 15 days of each 28-day cycle. Cisplatin is administered at a dose of 70 mg / m² on day 1 of the cycle after gemcitabine infusion on the background of hyperhydration.

At breast cancerGlands (locally advanced or metastatic) in the form of monotherapy for disease progression after first-line therapy, including anthracyclines in the absence of contraindications, the recommended dose of the drug is 1000-1200 mg / m² at 1, 8 and 15 days of each 28-day cycle. When used as part of a combination therapy as a first-line therapy for the progression of the disease after neoadjuvant and / or adjuvant therapy, including anthracyclines, the recommended dose of the drug is 1250 mg / m² in 1 and 8 days in combination with Paclitaxel, which is administered to gemcitabine at a dose of 175 mg / m² on day 1 of each 21-day cycle i / v drip for approximately 3 hours

At bladder cancer (locally advanced, metastatic and superficial) in the form of monotherapy, the recommended dose of the drug is 1250 mg / m² at 1, 8 and 15 days of each 28-day cycle.

When used as part of combination therapy, the recommended dose of the drug is 1000 mg / m² in 1, 8 and 15 days in combination with cisplatin, which is administered at a dose of 70 mg / m² immediately after gemcitabine infusion on day 1 or day 2 of each 28-day cycle.

For intravesical administration The recommended dose of the drug is 2000 mg. To obtain an instillation solution, the drug is dissolved in 100 or 50 ml of 0.9% sodium chloride solution to a concentration of from 20 to 40 mg / ml. Exposure of the drug is 60 minutes. Enter once a week for 6 weeks. The concentration of the solution should not exceed 40 mg / ml.

At epithelial ovarian cancer (locally advanced or metastatic) in the form of monotherapy recommended dose of the drug - 800-1250 mg / m² at 1, 8 and 15 days of each 28-day cycle. When used as part of combination therapy, the recommended dose of the drug is 1000 mg / m² on days 1 and 8 in combination with carboplatin at a dose of AUC4.0 mg / ml / min, which is administered immediately after gemcitabine infusion on day 1 of each 21-day cycle.

At pancreatic cancer (locally advanced or metastatic) in the form of monotherapy recommended dose of the drug - 1000 mg / m² once a week for 7 weeks followed by a weekly break. Then the drug is injected at 1, 8 and 15 days of each 28-day cycle. When used as part of a combination therapy for locally advanced cancer with sequential Chemotherapy and radiation therapy (neoadjuvant) and with metastatic cancer, gemcitabine is administered at a dose of 1250 mg / m² on days 1 and 8 of each 21-day cycle. Cisplatin is administered after administration of gemcitabine at a dose of 70 mg / m² on day 1 of the cycle on the background of overhydration. With locally advanced cancer with simultaneous chemotherapy and radiation therapy, gemcitabine is administered 1 time per week for 1-2 hours before the start of radiation therapy at a dose of 125 mg / m² with subsequent (immediately after gemcitabine administration) administration of cisplatin in a dose of 40 mg / m².

Before each administration of gemcitabine it is necessary to control the number of platelets, leukocytes and granulocytes in the blood. If signs of bone marrow depression are observed, treatment should be stopped or the dose adjusted.

If hematologic toxicity develops, the gemcitabine dose may be reduced, or the administration of the drug may be postponed in accordance with the following scheme.

Data proving that elderly people it is necessary to adjust the dose, not available, although gemcitabine clearance and elimination half-life change with age.

Apply gemcitabine to patients with hepatic insufficiency or with impaired renal function be careful, because There are no sufficient data on the use of the drug in this category of patients.

Moderate or moderate renal failure (glomerular filtration rate from 30 ml / min to 80 ml / min) does not have a noticeable effect on gemcitabine pharmacokinetics.

Gemcitabine use in children not studied

Only 0.9% sodium chloride solution (without preservatives) is used as a solvent.

To prepare the solution for infusion, the contents of the vial 200 mg are dissolved in not less than 5 ml, and 1 g in not less than 25 ml of 0.9% sodium chloride solution for injection. Each vial is gently shaken until the lyophilisate is completely dissolved. The resulting solution should be clear.

The maximum concentration of gemcitabine should not exceed 40 mg / ml. Solutions prepared with a concentration above 40 mg / ml may be accompanied by incomplete dissolution.

The prepared gemcitabine solution containing the desired dose of the drug is diluted with a 0.9% sodium chloride solution for injection in an amount sufficient to conduct a 30-minute IV infusion prior to administration.

Before parenteral administration, it is necessary to visually monitor the prepared solution for the presence of mechanical impurities and discoloration.

Side effect

Adverse reactions occurring more often than in isolated cases are listed according to the following gradation: very often (> 10%); often (> 1%, <10%); sometimes (> 0.1%, <1%); rarely (> 0.01%, <0.1%); extremely rare (<0.01%).

From the hemopoietic system: often - leukopenia, thrombocytopenia, anemia; very rarely - thrombocytosis.

From the digestive system: very often - nausea, vomiting, increased activity of hepatic transaminases, alkaline phosphatase; often - anorexia, diarrhea, constipation, stomatitis, increased bilirubin levels.

From the urinary system: Often – mild proteinuria and hematuria; rarely - renal failure, clinical signs and symptoms similar to hemolytic-uremic syndrome (decrease in hemoglobin level, thrombocytopenia, increased levels of bilirubin, creatinine, urea and / or serum LDH).

Dermatological reactions: often- rash, itching, alopecia.

On the part of the respiratory system: very often, shortness of breath; often - cough, rhinitis; sometimes - bronchospasm, interstitial pneumonia, pulmonary edema; rarely, acute respiratory distress syndrome.

Since the cardiovascular system: rarely - decrease in blood pressure, myocardial infarction, heart failure, arrhythmia.

From the side of the central nervous system: often - headache, drowsiness, insomnia.

Other: very often - flu-like syndrome, peripheral edema; often - fever, chills, asthenia, back pain, myalgia; sometimes - swelling of the face; very rarely - Anaphylactic reactions .

Contraindications to the use of the drug

- pregnancy;

- lactation period (breastfeeding);

- hypersensitivity to gemcitabine or other components of the drug.

WITH caution prescribe the drug in violation of the function of the liver and / or kidneys, inhibition of bone marrow hematopoiesis (including against the background of concomitant radiation or chemotherapy), acute infectious diseases of viral, fungal or bacterial nature.

Application for violations of the liver

Apply gemcitabine to patients with liver failure be careful, because There are no sufficient data on the use of the drug in this category of patients.

Application for violations of kidney function

Apply gemcitabine to patients with impaired renal function be careful, because There are no sufficient data on the use of the drug in this category of patients.

Moderate or moderate renal failure (glomerular filtration rate from 30 ml / min to 80 ml / min) does not have a noticeable effect on gemcitabine pharmacokinetics.

Pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation.

special instructions

Treatment with gemcitabine can only be carried out under the supervision of a physician with experience in the use of anticancer chemotherapy.

Before starting treatment, the absolute number of granulocytes should be at least 1500 / μl, platelets - at least 100 000 / μl.

To identify non-hematological toxicity, it is necessary to conduct regular examination of the patient and an assessment of the function of the liver and kidneys. Depending on the degree of toxicity, the dose can be reduced during each cycle or with the beginning of a new cycle in steps. The decision to postpone the next injection of the drug should be based on the clinical evaluation by the doctor of the dynamics of toxicity.

An increase in the duration of infusion and the frequency of injections leads to an increase in toxicity.

The introduction of gemcitabine with liver metastases, with a history of hepatitis and alcoholism, as well as with cirrhosis of the liver increases the risk of developing liver failure.

When the first signs of hemolytic-uremic syndrome occur, gemcitabine treatment should be discontinued.

Patients with lung cancer or with lung metastases have an increased risk of adverse effects from the respiratory system. At the first signs of pneumonitis or the appearance of infiltrates in the lungs, gemcitabine treatment should be stopped.

Women and men during gemcitabine treatment and for at least 6 months after therapy should use reliable methods of contraception.

Overdose

Treatment: antidote not known. Clinically acceptable toxicity was observed with the introduction of single doses up to 5.7 g / m² IV for 30 minutes every two weeks. If an overdose is suspected, the patient should be under constant medical supervision, including blood counting.If necessary, carry out symptomatic treatment.

Drug interaction

Gemcitabine has a radiosensitizing effect, so when using this drug during radiation therapy, we can expect an increase in radiation reactions. In the case of sequential chemoradiation therapy, gemcitabine can be started after the resolution of acute radiation reactions or at least one week after the end of radiation therapy.

Terms and conditions of storage

List B. The drug should be stored out of the reach of children at a temperature of 15 ° to 30 ° C; Do not refrigerate or freeze.

The prepared solution should be stored at a temperature of from 15 ° to 30 ° C for no more than 24 hours; do not refrigerate or freeze.