Expiration date: 10/2025

instruction for use

FC APPROVED by the Ministry of health of Russia 14.12.2000 Ave # 7B

Composition. Each bottle contains:

the active substance is: gemcitabine hydrochloride

excipients: mannitol, sodium acetate.

Description. White or almost white lump or powder. After preparation of the solution — transparent, colorless to light straw color solution.

Pharmacological properties.

Pharmacodynamics. Gemcitabine is an antimetabolite of a group of pyrimidine analogues.

Gemcitabine shows cycloparaffins, acting on the cells in S phase and G1/S.

Gemcitabine is metabolized inside the cell under the action of nukleozidkinaz with the formation of active difosfatnyh and trifosfatnogo nukleozidov. Difosfatnye the nucleoside ribonucleotide reductase, which acts as the sole catalyst for the reactions leading to the formation of deoxynucleosides required for DNA synthesis. Triphosphate nucleosides are actively competing with deoxycytidylate for incorporation into the molecules of DNA and RNA. After incorporation of intracellular metabolites of gemcitabine 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 lysis, known as apoptosis.

Pharmacokinetics. Gemcitabine is rapidly excreted in the urine, mainly as an inactive metabolite 2 ' - deoxy?2', 2'-diferencia. Less than 10% of the administered dose is found in the urine in the form of unchanged drug. The binding of gemcitabine to plasma proteins is insignificant.

Pharmacokinetic analysis of studies with single and multiple doses shows that the volume of distribution is largely dependent on gender. System clearance, which ranges from about 30 l/h/m2 to 90 l/h / m2, depends on age and gender. T1/2 ranges from 32 min to 94 min.

Indications for use. Bladder cancer non-small cell lung cancer gemcitabine in monotherapy or in combination with cisplatin is indicated as a first-line drug for the treatment of patients with locally advanced or metastatic non-small cell lung cancer pancreatic cancer.

Gemcitabine is indicated for the treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas.

Gemcitabine in monotherapy or in combination with other anticancer agents also shows activity in breast cancer, ovarian cancer, locally advanced small cell lung cancer and locally advanced refractory testicular cancer.

Contraindications. Hypersensitivity to the drug pregnancy and breastfeeding.

Dosage and administration. Bladder cancer. Gemcitabine is administered at a dose of 1250 mg / m2 / drip for 30 minutes in 1, 8, and 15 days every 28 days with monotherapy or at a dose of 1000 mg/m2 in 1, 8 and 15 days in combination with cisplatin, which is administered immediately after the introduction of gemcitabine at a dose of 70 mg / m2 in 1 or 2 day of each 28-day cycle. After that, repeat the 4-week cycles.

Non-small cell lung cancer.

Monotherapy: gemcitabine is administered at a dose of 1000 mg / m2 / drip for 30 min 1 time per week for 3 weeks, followed by a week break. After that, repeat the 4-week cycles.

Application in combination with cisplatin: gemcitabine is administered in/drip at a dose of 1250 mg/m2 for 30 minutes in 1 and 8 days of each 21-day cycle or at a dose of 1000 mg/m2 for 30 minutes in 1, 8 and 15 day of each 28-day cycle.

Pancreatic cancer. Gemcitabine is administered at a dose of 1000 mg / m2 / drip for 30 min 1 time per week for 7 weeks, followed by a week break. Subsequent cycles should consist of injections administered once a week for the next 3 weeks with a week break.

In patients receiving gemcitabine, before each dose is necessary to control the number of platelets, leukocytes and granulocytes in the blood. In the case of hematological toxicity, the dose of gemcitabine may be reduced, or its administration postponed in accordance with the following scheme:

Absolute number of granulocytes, x 106 / l		Platelet count, x 106 / l	% full dose
>1000	and	>100000	100
500 – 1000	or	50000 - 100000	75
<500	or	<50000	to postpone the introduction of

To detect non-hematological toxicity, it is necessary to conduct a regular examination of the patient and check the function of the liver and kidneys. Depending on the degree of toxicity of the dose can be reduced during each cycle or with the beginning of a new cycle in steps.

The decision to postpone the next administration of the drug should be based on the clinical assessment of the dynamics of toxicity by the doctor.

Elderly patient. There is no evidence to suggest that the dose should be adjusted in elderly patients, although CL gemcitabine and T1/2 change with age.

Patients with impaired liver and kidney function. Gemcitabine should be used with caution in patients with liver failure or impaired renal function. No studies were conducted in patients with significant liver and kidney dysfunction. Moderate or moderate renal failure (glomerular filtration rate 30-80 ml/min) has no noticeable effect on the pharmacokinetics of gemcitabine.

Children. The use of gemcitabine in children has not been studied.

Instructions for dilution. To prepare a solution of gemcitabine should be used only 0, 9% sodium chloride solution for injection without preservatives.

To dissolve 200 mg of gemcitabine, at least 5 ml is added to the vial, and 1 g is at least 25 ml of 0, 9% sodium chloride solution for injection. The vials are shaken until the lyophilized powder is completely dissolved.

The maximum concentration of gemcitabine should not exceed 40 mg/ml solution prepared with a concentration higher than 40 mg/ml, can be characterized by incomplete dissolution.

The prepared solution of gemcitabine containing the desired dose of the drug before administration is diluted with a sufficient amount of 0, 9% sodium chloride solution for injection for 30 min/infusion.

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

Interaction with other drugs and other forms of interaction. With the introduction of gemcitabine at a dose of 1 g / m2 (up to 6 weeks of treatment) on the background of radiation therapy on the chest in patients with non-small cell lung cancer, there was significant toxicity in the form of severe and potentially life-threatening esophagitis and pneumonia. The optimal regimen for the safe administration of gemcitabine in combination with therapeutic regimens of radiation therapy has not yet been determined.

Special instruction. It is shown that the increase in the duration of infusion and frequency of administration leads to greater toxicity.

In patients receiving gemcitabine, before each dose is necessary to control the number of platelets, leukocytes and granulocytes in the blood. If you find inhibition of bone marrow function under the influence of the drug, it is necessary to suspend treatment or adjust the dose.

Periodically, it is necessary to assess the function of the kidneys and liver.

Women and men during treatment with Gemzar should use reliable methods of contraception.

Side effect. From the bone marrow hematopoiesis: anemia, leukopenia and thrombocytopenia.

From the digestive system: nausea, vomiting, diarrhea, stomatitis, increased levels of liver enzymes in the blood serum.

From the genitourinary system: proteinuria, hematuria. Rarely in patients receiving gemcitabine, clinical signs and symptoms similar to hemolytic uremic syndrome were found. Treatment with gemcitabine should be discontinued when the first signs of microangiopathic hemolytic anemia, such as a sharp decrease in hemoglobin levels with concomitant thrombocytopenia and increased levels of bilirubin, creatinine, urea and/or lactate dehydrogenase in the blood serum. Renal disorders can be irreversible even after discontinuation of treatment, which may require hemodialysis.

From the skin and skin appendages: skin rashes, accompanied by itching, partial alopecia.

From the respiratory system: shortness of breath, rarely — bronchospasm. Interstitial pneumonia, pulmonary edema, and respiratory syndrome were rarely reported. If these symptoms occur, treatment with gemcitabine should be discontinued.

The body as a whole: very often there are flu-like symptoms, including fever, headache, myalgia, asthenia, anorexia. Against the background of treatment with gemcitabine, cough, rhinitis, malaise and increased sweating can be observed.

Hypersensitivity: anaphylactic reactions occur very rarely.

Cardiovascular system: the development of peripheral edema has often been reported. There were several cases of hypotension.

An overdose of the drug. The antidote for gemcitabine is unknown. Clinically acceptable toxicity was observed with the introduction of single doses up to 5, 7 g / m2 / in for 30 minutes every 2 weeks. In case of suspected overdose, the patient should be under constant medical supervision, including the calculation of the blood formula. If necessary, the patient is given symptomatic treatment.

Form release. Lyophilized powder in 200 mg or 1 g bottles.

Storage conditions. Unopened bottles should be stored at room temperature (below 30 &°C) in places inaccessible to children. The prepared solution of gemcitabine can be stored at room temperature (below 30°C) for 24 hours.the prepared solution of gemcitabine should not be frozen, because crystallization can occur.

Shelf life. 3 years. Do not use after the date stated on the package.

Conditions of supply of pharmacies. By prescription.

Name of manufacturer (importer). Lilly France, France. "Eli Lilly", France.

Storage conditions:

Not freeze.

Shelf life:

After cooking, at a temperature of 15-30 °C 24 h