Index of drugs

Treatment (in combination with cisplatin) of patients with locally advanced or metastatic bladder cancer. Treatment of patients with locally advanced or metastatic pancreatic adenoma. First-line treatment (in combination with cisplatin) of patients with locally advanced or metastatic non-small cell lung cancer; gemcitabine monotherapy can be considered in elderly patients or Grade 2 patients. Treatment (in combination with carboplatin) of patients with epithelial ovarian cancer in locally advanced or metastatic disease after failure of platinum-based chemotherapy least six months without relapse. Treatment (in combination with paclitaxel) of patients with non-surgical recurrence of breast cancer that is ineligible for surgery or with metastases who have relapsed after adjuvant / neoadjuvant chemotherapy including anthracyclines, or in the event of contraindications to their use.

1 ml concentrate for solution for infusion contains 40 mg gemcitabine (as hydrochloride).

Cytostatics from the pyrimidine antimetabolite group. Gemcitabine (dFdC) is transformed intracellularly by nucleoside kinases to active nucleosides: diphosphate (dFdCDP) and triphosphate (dFdCTP). The cytotoxic effect of the drug is related to the inhibition of DNA synthesis by both metabolites and is specific for the cell cycle (S phase). Incorporation of gemcitabine into the DNA strand completes DNA replication, leading to programmed cell death. After intravenous administration, gemcitabine is metabolised in the liver, kidneys, blood and other tissues by cytidine aminase. The main metabolite is inactive 2'-deoxy-2 ', 2'-difluorouridine (dFdU) - it is found in plasma and in urine. Intracellular metabolites (active diphosphate and gemcitabine triphosphate, inactive monophosphate) are not found in plasma and urine. Excretion occurs in the urine, mainly in the form of dFdU, in 10% unchanged form. T_0,5 depends on the age and sex of the patient, usually 42-94 min. Given once a week gemcitabine does not accumulate. The drug hardly binds to plasma proteins.

Hypersensitivity to gemcitabine or auxiliary substances of the preparation. Breastfeeding period.

The toxicity of the drug increases with increasing the infusion time and increasing their frequency. The morphological image of the blood (including the number of platelets, leukocytes and granulocytes) should be monitored prior to each subsequent dose of gemcitabine. If bone marrow suppression is detected, interruption or modification of treatment should be considered. When commencing treatment with gemcitabine, caution should be exercised in patients with bone marrow dysfunction. Periodically renal and hepatic function should be monitored (including virological test). Carefully apply gemcitabine in patients with hepatic impairment. Administration of the drug to patients with co-existing liver metastases or hepatitis, alcoholism or cirrhosis of the liver may lead to exacerbation of liver failure. Exercise caution in patients with impaired renal function. Drug treatment should be discontinued immediately after the first signs of microangiopathic haemolytic anemia, such as rapidly decreasing hemoglobin levels with concomitant thrombocytopenia, elevated bilirubin, creatinine, urea and LDH in the blood, which may indicate the development of haemolytic-uremic syndrome. In case of severe respiratory adverse reactions (pulmonary edema, interstitial pneumonitis, acute respiratory failure of adults - ARDS), gemcitabine should be discontinued. Special care should be taken in patients with a history of cardiovascular disease. Gemcitabine is not recommended for use in children <18 years of age due to insufficient data on safety and efficacy.

Do not use during pregnancy unless clearly necessary. Women of childbearing potential should use effective contraception during gemcitabine treatment.Breast-feeding is contraindicated during gemcitabine treatment. Gemcitabine may interfere with spermatogenesis. Men treated with gemcitabine are advised to use effective contraception during treatment and up to 6 months after treatment. Treatment with gemcitabine may result in infertility - the patient should be informed about the possibility of sperm preservation before starting treatment.

Very common: leukopenia, thrombocytopenia, anemia, dyspnoea, vomiting, nausea, ALT and AST elevation and alkaline phosphatase, allergic skin rash (often associated with pruritus), alopecia, haematuria, mild proteinuria, flu-like symptoms, edema and peripheral edema (in including swelling of the face). Common: febrile neutropenia, anorexia, headache, insomnia, drowsiness, cough, rhinitis, diarrhea, inflammation and sores in the mouth, constipation, increased bilirubin, pruritus, increased sweating, back pain, muscle pain, fever, weakness, chills. Uncommon: cerebrovascular stroke, arrhythmia (mainly supraventricular), heart failure, interstitial pneumonitis, bronchospasm, severe hepatotoxicity (including hepatic failure and death). Rare: myocardial infarction, hypotension, clinical manifestations of peripheral vasculitis, pulmonary edema, adult respiratory distress syndrome, increased GGT activity, severe skin reactions (including exfoliative and bullous lesions), ulceration, blisters and ulcer formation, exfoliation of the epidermis , acute renal failure, haemolytic-uremic syndrome, injection site reactions, radiation damage, recurrence of radiation symptoms. Very rare: thrombocytosis, anaphylactoid reactions, ischemic colitis, toxic epidermal necrolysis, Stevens-Johnson syndrome. The incidence of grade 3 and 4 haematological toxicity, especially neutropenia, and neutropenic fatigue and febrile is higher in combination with gemcitabine / Paclitaxel compared to paclitaxel monotherapy. In the case of combination therapy with Cisplatin, an increase in the incidence of grade 3 and 4 haematological toxicity was observed, compared to MVAC ( Methotrexate, vinblastine, doxorubicin, cisplatin). In the combination with carboplatin combination, an increase in the incidence of grade 3 and 4 haematological toxicity and an increased incidence of haemorrhagic and febrile neutropenia were observed, compared to carboplatin monotherapy. Sensory nerve neuropathy was more common in combination therapy than after carboplatin monotherapy.

Bladder cancer (combined treatment): gemcitabine at a dose of 1000 mg / m² pc., by intravenous infusion over 30 minutes on the 1st, 8th and 15th day of a 28-day treatment cycle, in combination with Cisplatin (70 mg / m² pc.) administered on day 1 of the cycle after gemcitabine infusion or on day 2 of the 28-day cycle. The 4-week treatment cycle can then be repeated.Pancreatic cancer: 1000 mg / m² pc. as an intravenous infusion over 30 minutes once a week for 7 consecutive weeks, followed by a week's break in treatment. In subsequent treatment cycles, gemcitabine is given once a week for 3 weeks, followed by a week of treatment interruption.Non-small cell lung cancer (monotherapy): 1000 mg / m² pc. as an intravenous infusion over 30 minutes once a week for 3 weeks, followed by a week's break in treatment. The 4-week treatment cycle is then repeated.Non-small cell lung cancer (combination therapy): gemcitabine at a dose of 1250 mg / m² pc. as an intravenous infusion over 30 mins on days 1 and 8 of the 21-day treatment cycle, in combination with cisplatin, which is administered at a dose of 75-100 mg / m² pc. once every 3 weeks (on day 1, after gemcitabine administration or on day 2).Breast cancer (combination therapy): paclitaxel at a dose of 175 mg / m² pc. in an intravenous infusion lasting about 3 hours on day 1, followed by gemcitabine at a dose of 1250 mg / m² pc. in a 30-minute intravenous infusion on days 1 and 8 of each 21-day cycle. Before starting treatment with gemcitabine plus Paclitaxel, the absolute number of granulocytes in the patient should be at least 1.5 cells x 10⁹/ L.Ovarian cancer (combination therapy): gemcitabine at a dose of 1000 mg / m² pc. in a 30-minute intravenous infusion on days 1 and 8 of each 21-day cycle.On the first day of the cycle, after completing the gemcitabine infusion, carboplatin should be administered until a field under the AUC curve of 4 mg / ml x min is obtained.Dose modification in case of symptoms of hematological toxicity. The haematological parameters (platelet count, granulocytes) should be determined before each dose of gemcitabine. Before the cycle begins, the absolute number of granulocytes should be not less than 1.5 x 10⁹/ l, and the number of platelets not less than 100 x 10⁹/ L. In the event of haematological toxicity, consideration should be given to delaying the Next dose or reducing the dose as outlined below.Dose modification during the cycle. Bladder cancer, lungs, pancreas. The drug is given at full dose when the absolute number of granulocytes is> 1 x 10⁹/ l, and platelets> 100 x 10⁹/ L. In the case of granulocytopenia 0.5-1.0 x 10⁹/ l or thrombocytopenia 50-100 x 10⁹/ l should be given 75% of the normal dose of the drug, and at the number of granulocytes <0.5 x 10⁹/ l or plates <50 x 10⁹/ l the dose should be skipped (the omitted dose should not be administered during the cycle until the absolute number of granulocytes reaches the value of at least 0.5 x 10⁹/ l, and the number of platelets 50 x 10⁹/ L).Breast cancer. The drug is administered at full dose when the absolute number of granulocytes is ≥ 1.2 x 10⁹/ l, and platelet count> 75 x 10⁹/ L. When the number of granulocytes is 1- <1.2 x 10⁹/ l or the number of plates 50-75 x 10⁹/ l 75% of the dose is given. When the number of granulocytes is 0.7- <1 x 10⁹/ l and platelet count ≥50 x 10⁹/ l 50% of the dose is administered and at the number of granulocytes <0.7 x 10⁹/ l or platelet count <50 x 10⁹/ skip the dose (missed dose should not be administered during the course of the cycle, treatment should be resumed on the first day of the next cycle if the absolute number of granulocytes reaches the value of at least 1.5 x 10⁹/ l, and the number of platelets 100 x 10⁹/ L).Ovarian cancer. The drug is given at full dose when the granulocyte count is> 1.5 x 10⁹/ l and platelet count ≥100 x 10⁹/ L. At a granulocyte count of 1-1.5 x 10⁹/ l or the number of plates 75- <100 x 10⁹/ l drug should be given 50% of the dose, and with the number of granulocytes <1 x 10⁹/ l or platelet count <75 x 10⁹/ skip the dose (missed dose should not be administered during the course of the cycle, treatment should be resumed on the first day of the next cycle if the absolute number of granulocytes reaches the value of at least 1.5 x 10⁹/ l, and the number of platelets 100 x 10⁹/ L).Dose modification in subsequent treatment cycles. If the following signs of hematological toxicity occur, the dose of gemcitabine should be reduced to 75% of the initial dose given in the first cycle: absolute granulocytes <0.5 x 10⁹/ l for more than 5 days, absolute number of granulocytes <0.1 x 10⁹/ l for more than 3 days, febrile neutropenia, platelet count <25 x 10⁹/ l, cycle delay longer than 1 week due to toxicity. Dosage for non-haematological reasons can be reduced in the next cycle or during the course of the cycle, to the patient's safety and individual tolerability. The use of reduced doses should be continued until the symptoms of toxicity are reduced.
Before serving, concentrate for making sol. to inf. it should be properly diluted. It is recommended to administer the drug to a large vein to prevent damage to the blood vessel and extravasation. In the case of extravasation of the drug, the infusion should be stopped immediately and continued from another injection, and the patient should be closely monitored after treatment.