Description
Pharmacological action
antitumor agent . It has a cytostatic effect, which is associated with inhibition of DNA synthesis. In the cell, it is metabolized to active diphosphate and triphosphate nucleosides. Diphosphate nucleosides inhibit the action of ribonucleotide reductase, with the participation of which deoxynucleoside triphosphates necessary for DNA synthesis are formed in the cell, which leads to a decrease in their concentration in the cell. Triphosphate nucleosides actively compete for inclusion in the DNA chain, and can also be included in RNA. After the intracellular metabolites of gemcitabine are inserted into the DNA chain, one additional nucleotide is added to its growing chains, which leads to complete inhibition of further DNA synthesis and programmed cell death.
Indications
– Locally advanced or metastatic non-small cell lung cancer as a first-line therapy in combination with cisplati Mr. and carboplatin, as well as in monotherapy in elderly patients with a functional status of 2.
– Unresectable, local recurrent or metastatic breast cancer as part of combination therapy with paclitaxel after neoadjuvant and / or adjuvant therapy, including anthracyclines, in the absence of contraindications to their appointment.
– Locally advanced or metastatic urothelial cancer (cancer of the bladder, renal pelvis, ureter, urethra).
– Locally or metastatic epithelial ovarian cancer as monotherapy or in combination with carboplatin in patients with disease progression after the first line of therapy based on platinum derivatives.
– Locally advanced or metastatic pancreatic cancer.
– Locally advanced or metastatic cervical cancer.
– Cancer of the biliary tract.
Gemcitabine has been shown to be effective in advanced small cell lung cancer and advanced refractory testicular cancer.
Contraindications
– Hypersensitivity to gemcitabine or other components of the
preparation – pregnancy and lactation period
– children under 18 years of age (lack of sufficient experience of use)
Caution: In case of impaired liver and / or kidney function, bone marrow depression (depression) including against the background of concomitant radiation or chemotherapy), acute infectious diseases of a viral, fungal or bacterial nature (including chicken pox, shingles), in patients with cardiac o-vascular diseases (including a history).
Composition
1 vial – gemcitabine (in the form of hydrochloride) – 200 mg
Dosage and administration of
Gemcitabine is administered intravenously dropwise for 30 minutes.
Before each administration of gemcitabine, it is necessary to control the number of platelets, white blood cells and granulocytes in the blood. With signs of inhibition of bone marrow function caused by the drug, it is necessary to suspend treatment or adjust the dose.
Non-small cell lung cancer (locally or metastatic), first line of therapy
Monotherapy
The recommended dose 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 the first day of the cycle after the infusion of gemcitabine against a background of hyperhydration.
Combination therapy with carboplatin: the recommended dose is 1000 mg / m2 or 1250 mg / m2 on days 1 and 8 of each 21-day cycle. Carboplatin is introduced from the calculation of AUC (area under the concentration-time curve) 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 a 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 for 3 hours on the 1st day of the 21-day cycle, followed by the introduction of gemcitabine. The recommended dose of the drug is 1250 mg / m2 on the 1st and 8th day 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, metastatic and superficial), renal pelvis, ureter, urethra)
Monotherapy
The recommended dose is 1250 mg / m2 on days 1, 8 and 15 of each 28-day cycle.
Combination therapy with cisplatin
Recommended dose 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 the infusion of gemcitabine on 1 or 2 days of each 28-day cycle. Clinical studies have shown that at doses of cisplatin 100 mg / m2, more pronounced myelosuppression is observed.
Epithelial ovarian cancer (locally or metastatic, resistant to platinum derivatives)
Monotherapy
The recommended dose is 800-1250 mg / m2 on days 1, 8 and 15 of each 28-day cycle.
Combined therapy with carboplatin
The recommended dose is 1000 mg / m2 on days 1 and 8 in combination with carboplatin at AUC 4.0 mg / ml / min, which is administered immediately after gemcitabine infusion on day 1 of every 21-day cycle.
Pancreatic cancer (locally or metastatic, incl. resistant to fluorouracil therapy)
Monotherapy
The recommended dose is 1000 mg / m2 once a week for 7 weeks, followed by a weekly break. Then the drug is administered on the 1st, 8th and 15th days of each 28-day cycle.
Cervical cancer (locally or metastatic)
Combination therapy with cisplatin
For locally advanced cancer with sequential chemoradiotherapy (neoadadovant) and for metastatic cancer, cisplatin is administered at a dose of 70 mg / m2 after 1 day of hemodization against the background.
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 by (immediately after cisplatin) gemcitabine. Gemcitabine is administered once a week 1-2 hours before the start of radiation therapy at a dose of 125 mg / m2.
Cancer of the biliary tract
Combination therapy with cisplatin
Cisplatin is administered at a dose of 70 mg / m2 on the 1st day of the cycle amid hyperhydration followed by gemcitabine. Gemcitabine is administered at a dose of 1250 mg / m2 on the 1st and 8th day of each 21-day cycle.
Dose adjustment
If hematologic toxicity develops, the dose of Gemcitar ® may be reduced or its administration may be delayed in accordance with the following schemes:
A. Dose adjustment of gemcitabine within the cycle for urothelial cancer, non-small cell lung cancer, pancreatic cancer in monotherapy or in combination with cisplatin
Absolute granulocyte count
(x 109 / l)
Platelet count
(x 109 / l)
% of previous dose
> 1
100 and
> 100 5-1
or
50-100
75
<0.5 or <50 Postpone the administration of B. Correction of the dose of gemcitabine in the breast cancer cycle in combination with paclitaxel Absolute number of granulocytes x 109 / x l) Platelet count (x 109 / l) % of previous dose 1.2 and 75 100 1- <1.2 or 5 0-75 75 0.7- <1 and 50 50 <0.7 or <50 delay the introduction of B. Dose adjustment of gemcitabine in the cycle for ovarian cancer in combination with carboplatin Absolute granulocyte count (x 109 / l) Platelet count (x 109 / l) % of the previous dose > 1.5
and
and 100
100
1-1.5
or
75-100
50
<1 or <75 Postpone the administration of To detect non-hematologic toxicity, regular examination of the patient should be performed and liver and kidney function should be monitored. Depending on the degree of toxicity, the dose can be reduced stepwise during each cycle or with the start of a new cycle. The introduction of the drug should be delayed until, in the opinion of the doctor, toxicity is resolved. Special patient groups Elderly patients No data suggesting that in elderly patients it is necessary to adjust the dose. Patients with impaired liver and kidney function Use gemcitabine in patients with hepatic impairment or impaired renal function with caution, since there are 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) does not significantly affect the pharmacokinetics of gemcitabine. Children Gemcitabine has been studied in limited studies of phase I and II in children with various types of neoplasms. The data from these studies are insufficient to prove the efficacy and safety of gemcitabine in children. Side effects Side reactions that occurred more often than in single cases are listed according to the following gradation: very often (> 10%) often (> 1%, <10%) sometimes (> 0.1%, <1 %) rarely (> 0.01%, <0.1%) very rarely (<0.01%). From the blood and lymphatic systems: very often – anemia, leukopenia and thrombocytopenia often – febrile neutropenia very rarely – thrombocytosis. On the part of the immune system: very rarely – anaphylactic reaction. From the side of metabolism and nutrition: often – anorexia. From the nervous system: often – headache, insomnia, drowsiness infrequently – cerebrovascular accident very rarely – reversible posterior encephalopathy syndrome. From the side of the heart: infrequently – heart failure, arrhythmia, mainly supraventricular rarely – myocardial infarction. From the vascular side: very often – edema, peripheral edema rarely – lowering blood pressure, peripheral vasculitis, gangrene very rarely – syndrome of increased permeability of capillaries. From the respiratory system: very often – shortness of breath often – cough, rhinitis, infrequently – bronchospasm, rarely interstitial pneumonitis – pulmonary edema, adult respiratory distress syndrome. From the gastrointestinal tract: very often – nausea, vomiting, increased activity of the liver enzymes aspartate aminotransferase (ACT), alanine aminotransferase (ALT) and alkaline phosphatase often – diarrhea, stomatitis, ulcerative lesions of the oral mucosa, constipation, increased bilirubin concentration , infrequently – severe hepatotoxicity, including liver failure, in some cases with a fatal outcome rarely – increased concentration of gammaglutamyl transferase (GGT) is very rare – ischemic colitis. From the side of the skin and skin appendages: very often – allergic skin rashes of a mild degree, accompanied by itching alopecia (usually minimal hair loss) often itching, sweating rarely – ulcers, vesicle formation, desquamation, severe skin reactions, including desquamation and bullous skin lesions very rarely – toxic epidermal necrolysis, Stevens-Johnson syndrome. On the part of the kidneys and urinary tract: very often – mild proteinuria and hematuria, infrequently – renal failure rarely – increased concentrations of creatinine, urea and lactate dehydrogenase (LDH) in hemolytic-uremic syndrome. From the side of the musculoskeletal system and connective tissue: often – back pain, myalgia. Other: very common – flu-like syndrome. Cases of malaise have also been reported, sweating often – fever, asthenia, chills rarely – reactions at the injection site are mostly mild. Hypersensitivity: Anaphylactoid reactions have been reported very rarely. Radiation toxicity has been reported rarely (see section Interaction with other types of therapy). The use of gemcitabine in combination with paclitaxel for breast cancer Adverse events of III severity Hematological toxicity: anemia – 5.7%, thrombocytopenia – 5.3%, neutropenia -31.3%. Non-hematologic toxicity: febrile neutropenia – 4.6%, increased fatigue – 5.7%, diarrhea – 3.1%, motor neuropathy – 2.3%, sensory neuropathy – 5.3%. Adverse events of the IV severity Hematological toxicity: anemia – 1.1%, thrombocytopenia – 0.4%, neutropenia – 17.2% (grade IV neutropenia lasting more than 7 days was recorded in 12.6% of patients). Non-hematologic toxicity: febrile neutropenia – 0.4%, increased fatigue – 0.8%, motor neuropathy – 0.4%, sensory neuropathy – 0.4%. The use of gemcitabine in combination with cisplatin for bladder cancer Adverse events III severity Hematological toxicity: anemia – 24%, thrombocytopenia – 29%. Non-hematologic toxicity: nausea and vomiting – 22%, diarrhea – 3%, infection – 2%, stomatitis – 1%. Adverse events of the IV severity Hematological toxicity: anemia – 4%, thrombocytopenia – 29%. Non-hematologic toxicity: infection – 1%. The use of gemcitabine in combination with carboplatin in ovarian cancer Adverse events III severity Hematological toxicity: anemia – 22.3%, neutropenia – 41.7%, thrombocytopenia – 30.3%, leukopenia – 48.0% Non-hematologic toxicity: bleeding – 1.8%, febrile neutropenia – 1.1%. Adverse events of the IV severity Hematological toxicity: anemia – 5.1%, neutropenia – 28.6%, thrombocytopenia – 4.6%, leukopenia – 5.1%. Non-hematologic toxicity: infection without neutropenia – 0.6% Overdose Clinically acceptable toxicity was observed with single doses up to 5.7 g / m2 intravenously for 30 minutes every 2 weeks. Symptoms: myelosuppression, paresthesia, severe skin rash, hemorrhagic syndrome. Treatment: there is no specific antidote. If an overdose is suspected, the patient should be under constant medical supervision, including a general blood test with a leukocyte determination, if necessary, symptomatic treatment is carried out. Storage conditions Store in a dark place at a temperature not exceeding 30 ° C. Store the prepared solution of the drug at a temperature not exceeding 30 ° C for no more than 24 hours. Keep out of the reach of children. active substance Gemcitabine Terms and conditions prescription
