Gemzar, 200 mg, lyophilisate for solution for infusion, 10 ml, 1 pc.

Gemzar

Active substance:

Gemcitabine*

Pharmgroup:

Antimetabolites

Gemzar®

Gemcitabine is administered intravenously over 30 minutes.

Before each administration of gemcitabine, it is necessary to monitor the number of platelets, leukocytes and granulocytes in the blood. If there are signs of bone marrow suppression caused by the drug, it is necessary to suspend treatment or adjust the dose.

Non-small cell lung cancer (locally advanced or metastatic), first line of therapy.

Monotherapy:

The recommended dose of the drug is 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle.

Combination therapy with cisplatin:

The recommended dose of the drug is 1250 mg/m2 on days 1 and 8 of each 21-day cycle or 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle. Cisplatin is administered at a dose of 70 mg/m2 on day 1 of the cycle after gemcitabine infusion against the background of hyperhydration.

Combination therapy with carboplatin:

The recommended dose of the drug is 1000 mg/m2 or 1200 mg/m2 on days 1 and 8 of each 21-day cycle. Carboplatin is administered at an AUC (area under the concentration-time curve) of 5.0 mg/ml/min on day 1 of the cycle after gemcitabine infusion.

Breast cancer (unresectable, locally recurrent or metastatic). Combination therapy with paclitaxel:

As first-line therapy for disease progression after neoadjuvant and/or adjuvant therapy, including anthracyclines, in the absence of contraindications to them. Paclitaxel is administered at a dose of 175 mg/m2 intravenously over 3 hours on day 1 of a 21-day cycle, followed by gemcitabine. The recommended dose of the drug is 1250 mg/m2 on days 1 and 8 of each 21-day cycle. Before starting combination therapy (gemcitabine + paclitaxel), the absolute number of granulocytes in the blood of patients should be at least 1500/μl.

Urothelial cancer (bladder cancer (locally advanced, metastatic and superficial), renal pelvis, ureter, urethra).

Monotherapy:

The recommended dose of the drug is 1250 mg/m2 on days 1, 8 and 15 of each 28-day cycle.

Combination therapy with cisplatin:

The recommended dose of the drug is 1000 mg/m2 on days 1, 8 and 15 in combination with cisplatin, which is administered at a dose of 70 mg/m2 immediately after gemcitabine infusion on days 1 or 2 of each 28-day cycle. Clinical studies have shown that with a dose of cisplatin of 100 mg/m2, more pronounced myelosuppression is observed.

Epithelial ovarian cancer (locally advanced or metastatic, resistant to platinum derivatives).

Monotherapy:

The recommended dose of the drug is 800-1250 mg/m2 on days 1, 8 and 15 of each 28-day cycle. Combination therapy with carboplatin:

The recommended dose of the drug is 1000 mg/m2, on days 1 and 8, in combination with carboplatin at an AUC of 4.0 mg/ml/min, which is administered immediately after gemcitabine infusion on day 1 of each 21-day cycle.

Pancreatic cancer (locally advanced or metastatic, including resistant to fluorouracil therapy).

Monotherapy:

The recommended dose of the drug is 1000 mg/m2 once a week for 7 weeks, followed by a one-week break. The drug is then administered on days 1, 8 and 15 of each 28-day cycle.

Cervical cancer (locally advanced or metastatic).

Combination therapy with cisplatin:

For locally advanced cancer with sequential chemoradiation therapy (neoadjuvant) and for metastatic cancer, cisplatin is administered at a dose of 70 mg/m2 on day 1 of the cycle against the background of hyperhydration, followed by gemcitabine. Gemcitabine is administered at a dose of 1250 mg/m2 on days 1 and 8 of each 21-day cycle.

For locally advanced cancer with concurrent chemoradiation, cisplatin is administered at a dose followed (immediately after administration of cisplatin) by administration of gemcitabine. Gemcitabine is administered once a week 1-2 hours before the start of radiation therapy at a dose of 125 mg/m2.

Biliary tract cancer

Combination therapy with cisplatin:

Cisplatin is administered at a dose of 70 mg/m2 on day 1 of the cycle against the background of hyperhydration, followed by the administration of gemcitabine. Gemcitabine is administered at a dose of 1250 mg/m2 on days 1 and 8 of each 21-day cycle.

Dose adjustment

In case of hematological toxicity development

The dose of gemcitabine may be reduced or its administration delayed according to the following regimens:
A. Cycle dose adjustment of gemcitabine for urothelial cancer, non-small cell lung cancer, pancreatic cancer as monotherapy or in combination with cisplatin. Gemcitabine dose adjustment within a cycle for urothelial cancer, non-small cell lung cancer, pancreatic cancer as monotherapy or in combination with cisplatin

B. Intra-cycle dose adjustment of gemcitabine for breast cancer in combination with paclitaxel.

Intra-cycle dose adjustment of gemcitabine for breast cancer in combination with paclitaxel

B. Intra-cycle dose adjustment of gemcitabine for ovarian cancer in combination with carboplatin.

Intra-cycle dose adjustment of gemcitabine for ovarian cancer in combination with carboplatin

To detect non-hematological toxicity, it is necessary to regularly evaluate the patient and monitor liver and kidney function. Depending on the degree of toxicity, the dose can be reduced during each cycle or at the start of a new cycle in steps.

Administration of the drug should be delayed until, in the judgment of the physician, toxicity has resolved.

Special patient groups

Elderly patients:

There are no data to suggest that dosage adjustments are necessary in elderly patients.

Patients with impaired liver and kidney function:

Gemcitabine should be used with caution in patients with liver failure or impaired renal function, since there is no sufficient data on the use of the drug in this category of patients. Mild or moderate renal failure (glomerular filtration rate from 30 ml/min to 80 ml/min ) has no significant effect on the pharmacokinetics of gemcitabine.

Children:

Gemcitabine has been studied in limited phase I and II studies in children with various types of neoplasms. Data from these studies are insufficient to demonstrate the effectiveness and safety of gemcitabine in children.

Recommendations for preparing solution for infusion

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

To prepare a solution for infusion, the contents of a 200 mg bottle are dissolved in no less than 5 ml, and 1 g in no less than 25 ml of 0.9% sodium chloride solution for injection. Each bottle is gently shaken until the lyophilisate is completely dissolved. The resulting solution should be transparent.

The maximum concentration of gemcitabine should not exceed 40 mg/ml. Solutions prepared with concentrations higher than 40 mg/ml may be accompanied by incomplete dissolution. The prepared solution of gemcitabine, containing the required dose of the drug, is diluted with 0.9% sodium chloride solution for injection before administration in an amount sufficient for a 30-minute intravenous infusion.

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

Instructions:

pharmachologic effect

Pharmacological action - antitumor, cytostatic.

Contraindications

Hypersensitivity, pregnancy, breastfeeding.

Use during pregnancy and breastfeeding

Contraindicated during pregnancy.

FDA category of effect on the fetus is D.

Breastfeeding should be stopped during treatment.

Side effects of the drug

From the nervous system and sensory organs: headache, drowsiness, insomnia.

From the cardiovascular system and blood (hematopoiesis, hemostasis): myelosuppression (anemia, leukopenia, thrombocytopenia), decreased blood pressure, arrhythmia, heart failure, myocardial infarction, bleeding (occurred mainly in patients with pancreatic cancer).

From the respiratory system: bronchospastic reactions (shortness of breath, difficulty breathing, chest tightness and/or stertorous breathing), toxic effects on the lung parenchyma or pneumonitis (cough, shortness of breath), pulmonary edema (cough, difficulty breathing).

From the gastrointestinal tract: nausea, vomiting (69% of cases), diarrhea (19%), constipation, stomatitis (≤11%), increased activity of liver transaminases and alkaline phosphatase.

From the genitourinary system: proteinuria, hematuria, peripheral edema (fingers, toes or ankles); in rare cases, edema can be generalized; rarely - renal failure, hemolytic-uremic syndrome (decreased hemoglobin, thrombocytopenia, hyperbilirubinemia, hypercreatinemia, increased LDH activity and urea concentration).

From the skin: rash (30%), alopecia (usually minor), skin rashes, itching.

Other: often (41%) - flu-like syndrome (fever, headache, back pain, chills, myalgia, weakness, anorexia, catarrhal symptoms, sweating), infection (16%), less often - paresthesia, extravasate formation (irritation, pain or redness) at the injection site, drowsiness, rarely - Gasser's disease (black tarry stools, blood in the urine or stool, increased body temperature, increased or decreased urination, pinpoint red spots on the skin, swelling of the face, fingers, toes or ankles, unusual bleeding or bruising, unusual tiredness or weakness, yellowing of the sclera or skin).

Precautionary measures

The use of gemcitabine should be carried out under strict monitoring of blood counts (once every 2 weeks). If the number of leukocytes decreases <1500/mm3 and platelets <100,000/mm3, dose adjustment is required. The indication for discontinuation of the drug is a decrease in the number of leukocytes <500/mm3 and platelets <50,000/mm3.

If gemcitabine-induced pneumonitis is confirmed or suspected, treatment should be discontinued immediately.

Women of childbearing potential should use effective contraception (possible teratogenicity).

Use with caution in elderly people (increased risk of toxic effects on the blood), in patients who have previously received cytotoxic drugs or radiation therapy. You should refrain from potentially dangerous activities that require increased attention and speed of mental and motor reactions.

During the treatment period, vaccination with viral vaccines is not recommended. Prescription of viral vaccines is possible no earlier than 3 months - 1 year after stopping the use of the drug. Immunization with oral polio vaccine should be delayed in people who are close contacts of the patient, especially family members.

Signs of bone marrow suppression, unusual bleeding or hemorrhage, black tarry stools, blood in the urine or stool, or pinpoint red spots on the skin require immediate medical consultation.

Dental interventions must be completed before starting therapy or postponed until the blood picture normalizes. During treatment, be careful when using toothbrushes, floss or toothpicks.

When gemcitabine is used more than once per week or when the infusion is administered over more than 60 minutes, adverse effects associated with gemcitabine therapy may occur more frequently and be more severe.

Previous treatment with cytostatics increases the incidence and severity of leukopenia and thrombocytopenia (a progressive decrease in the number of leukocytes and platelets may occur after completion of therapy).

The use of gemcitabine should be carried out by specially trained medical personnel, observing established precautions when preparing, diluting injection solutions (in a sterile box using disposable surgical gloves and masks) and destroying needles, syringes, vials, ampoules and the remainder of the unused drug.

If gemcitabine accidentally comes into contact with the skin or mucous membranes, the affected area should be immediately washed with soap and water or thoroughly with a strong stream of water, respectively.

Storage conditions of the drug

List B.: At a temperature of 15–30 °C. Do not freeze.

Gemzar, 200 mg, lyophilisate for solution for infusion, 10 ml, 1 pc.

Gemcitabine is administered intravenously over 30 minutes.

Before each administration of gemcitabine, it is necessary to monitor the number of platelets, leukocytes and granulocytes in the blood. If there are signs of bone marrow suppression caused by the drug, it is necessary to suspend treatment or adjust the dose.

Non-small cell lung cancer

(locally advanced or metastatic), first line of therapy.

Monotherapy: The recommended dose of the drug is 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle.

Combination therapy with cisplatin: The recommended dose of the drug is 1250 mg/m2 on days 1 and 8 of each 21-day cycle or 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle. Cisplatin is administered at a dose of 70 mg/m2 on day 1 of the cycle after gemcitabine infusion against the background of hyperhydration.

Combination therapy with carboplatin: The recommended dose of the drug is 1000 mg/m2 or 1200 mg/m2 on days 1 and 8 of each 21-day cycle.

Carboplatin is administered at an AUC (area under the concentration-time curve) of 5.0 mg/ml/min on day 1 of the cycle after gemcitabine infusion.

Mammary cancer

(unresectable, locally recurrent or metastatic).

Combination therapy with paclitaxel: As first-line therapy for disease progression after neoadjuvant and/or adjuvant therapy including anthracyclines, in the absence of contraindications to them. Paclitaxel is administered at a dose of 175 mg/m2 intravenously over 3 hours on day 1 of a 21-day cycle, followed by gemcitabine. The recommended dose of the drug is 1250 mg/m2 on days 1 and 8 of each 21-day cycle.

Before starting combination therapy (gemcitabine + paclitaxel), the absolute number of granulocytes in the blood of patients should be at least 1500/μl.

Urothelial cancer

(cancer of the bladder (locally advanced, metastatic and superficial), renal pelvis, ureter, urethra).

Monotherapy: The recommended dose of the drug is 1250 mg/m2 on days 1, 8 and 15 of each 28-day cycle.

Combination therapy with cisplatin: The recommended dose of the drug is 1000 mg/m2 on days 1, 8 and 15 in combination with cisplatin, which is administered at a dose of 70 mg/m2 immediately after gemcitabine infusion on days 1 or 2 of each 28-day cycle. Clinical studies have shown that with a dose of cisplatin of 100 mg/m2, more pronounced myelosuppression is observed.

Epithelial ovarian cancer

(locally advanced or metastatic, resistant to platinum derivatives).

Monotherapy: The recommended dose of the drug is 800–1250 mg/m2 on days 1, 8 and 15 of each 28-day cycle.

Combination therapy with carboplatin: The recommended dose of the drug is 1000 mg/m2, on days 1 and 8 in combination with carboplatin at an AUC of 4.0 mg/ml/min, which is administered immediately after gemcitabine infusion on day 1 of each 21-day cycle.

Pancreas cancer

(locally advanced or metastatic, including resistant to fluorouracil therapy).

Monotherapy: The recommended dose of the drug is 1000 mg/m2 once a week for 7 weeks, followed by a one-week break. The drug is then administered on days 1, 8 and 15 of each 28-day cycle.

Cervical cancer

(locally advanced or metastatic).

Combination therapy with cisplatin: For locally advanced cancer with sequential chemoradiotherapy (neoadjuvant) and for metastatic cancer, cisplatin is administered at a dose of 70 mg/m2 on day 1 of the cycle against the background of hyperhydration, followed by gemcitabine. Gemcitabine is administered at a dose of 1250 mg/m2 on days 1 and 8 of each 21-day cycle.

For locally advanced cancer with simultaneous chemoradiotherapy, cisplatin is administered at a dose of 40 mg/m2 followed (immediately after the administration of cisplatin) by the administration of gemcitabine. Gemcitabine is administered once a week 1–2 hours before the start of radiation therapy at a dose of 125 mg/m2.

Biliary tract cancer

Combination therapy with cisplatin: Cisplatin is administered at a dose of 70 mg/m2 on day 1 of the cycle against the background of hyperhydration, followed by the administration of gemcitabine. Gemcitabine is administered at a dose of 1250 mg/m2 on days 1 and 8 of each 21-day cycle.

Dose adjustment

If hematologic toxicity occurs, the dose of gemcitabine may be reduced or its administration delayed according to the following regimens:

A. Dose adjustment of gemcitabine within a cycle for urothelial cancer, non-small cell lung cancer, pancreatic cancer as monotherapy or in combination with cisplatin.

B. Intra-cycle dose adjustment of gemcitabine for breast cancer in combination with paclitaxel.

B. Intra-cycle dose adjustment of gemcitabine for ovarian cancer in combination with carboplatin.

To detect non-hematological toxicity, it is necessary to regularly evaluate the patient and monitor liver and kidney function. Depending on the degree of toxicity, the dose can be reduced during each cycle or at the start of a new cycle in steps.

Administration of the drug should be delayed until, in the judgment of the physician, toxicity has resolved.

Special patient groups

Elderly patients:

There are no data to suggest that dosage adjustments are necessary in elderly patients.

Patients with impaired liver and kidney function:

Gemcitabine should be used with caution in patients with liver failure or impaired renal function, since there is no sufficient data on the use of the drug in this category of patients.

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

Children:

Gemcitabine has been studied in limited phase I and II studies in children with various types of neoplasms. Data from these studies are insufficient to demonstrate the effectiveness and safety of gemcitabine in children.

Recommendations for preparing solution for infusion

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

To prepare the concentrate, the contents of a 200 mg bottle are dissolved in no less than 5 ml, and 1 g in no less than 25 ml of 0.9% sodium chloride solution for injection. Each bottle is gently shaken until the lyophilisate is completely dissolved. The resulting solution should be transparent.

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

The prepared gemcitabine concentrate containing the required dose of the drug is diluted before administration with 0.9% sodium chloride solution for injection in an amount sufficient for a 30-minute intravenous infusion.

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