Tations

Active material: Gemcitabine
When ATH: L01BC05
CCF: Anticancer drug. Antimetaʙolit
ICD-10 codes (testimony): C25, C34, C50, C56, C62, C67
When CSF: 22.02.03
Manufacturer: DR. REDDY`S LABORATORIES LTD. (India)

Pharmaceutical form, composition and packaging

Valium for solution for infusion white or nearly white, in the form of individual units or lozenges, or in the form of loose powder, free from visible foreign particles.

Excipients: mannitol, sodium acetate, Sodium hydroxide.

Bottles of colorless glass (1) – packs cardboard.

Pharmacological action

Anticancer drug. Pyrimidine analog antimetabolite group.

The drug inhibits the synthesis of DNA. Shows tsiklospetsifichnost, acting on the cells in S phase and G1 / S. It is metabolized in the cell under the influence of nucleoside kinases to active diphosphate and triphosphate nucleosides.

Nucleoside diphosphate inhibits ribonucleotide reductase – single enzyme, catalyzes the formation of deoxynucleoside triphosphates, required for DNA synthesis.

Triphosphate nucleosides can be integrated into the DNA chain (less RNA), which leads to the cessation of further DNA synthesis and programmed cell lysis (apoptosis).

Gemcitabine is also a powerful means of radio-even at concentrations lower, than cytotoxic.

Pharmacokinetics

Distribution

V_d a significant extent depends on the duration of infusion and sex of the patient. Plasma protein binding is low – less 10%.

Metabolism

It is metabolized in the liver cells, kidney, blood by the enzyme cytidine deaminase stages, to formations neaktivnogo metabolite 2-deoxy-2.2-diftoruridina.

Deduction

Systemic clearance, which ranges, about, from 30 l / h / m² to 90 l / h / m², It depends on the age and sex of the patient (women on clearance 25% less, than men; age gemcitabine clearance decreases).

T_1/2 ranging from 42 minutes to 94 m. Displayed, mainly, urine as an inactive metabolite of 2-deoxy-2,2-diftoruridina – 89%, and in unaltered form – less 10%; the feces appears less 1%.

Pharmacokinetics in special clinical situations

When a reduced renal function in the body can accumulate inactive metabolite.

Testimony

- Non-small cell lung cancer;

- Mammary cancer;

- Pancreatic cancer;

- Bladder cancer.

Gemcitabine monotherapy or in combination with other antitumor agents is also active in ovarian cancer, locally advanced small cell lung cancer and refractory testicular cancer Locally.

Dosage regimen

Tsitogem should be administered in / in drip for 30 m.

Gemcitabine is part of many chemotherapeutic regimes in connection with the selection of dose and mode of administration in each individual case should be referred to the literature.

Non-small cell lung cancer

As a single agent recommended dose is 1000 mg / m² 1 once a week for 3 weeks followed by one week apart, every 28 days. In combination with cisplatin and gemcitabine is administered in a dose of 1250 mg / m² in the 1st and 8th days of each 21-day cycle or a dose 1000 mg / m² in 1, 8 and 15th days of each 28-day cycle.

Mammary cancer

With the progression of the disease after first-line therapy, consisting of anthracyclines or without (Side effects when anthracyclines) gemcitabine is used in monotherapy at a dose 1000-1200 mg / m² in 1, 8 and 15th days of each 28-day cycle. In combination with the drug is paclitaxel administered at a dose 1250 mg / m² in the 1st and 8th days of each 21-day cycle.

Pancreatic cancer

The recommended dose – 1000 mg / m² 1 once a week for 7 weeks followed by one week apart. Subsequent cycles should consist of infusions, conducted 1 once a week for 3 weeks, followed by one week apart.

Bladder Cancer

The recommended dose – 1250 mg / m² in 1, 8 and 15th days of each 28 days as monotherapy or 1000 mg / m² in 1, 8 and 15 days in combination with cisplatin, which is inserted immediately after injection of gemcitabine at a dose 70 mg / m² in the 1st or 2nd day of each 28-day cycle.

In the case of hematological toxicity of gemcitabine dose can be reduced or its administration delayed according to the following scheme: when the amount of granulocyte >1000/l and platelet >100 000/l use the full recommended dose. When the number of granulocytes 500-1000 / l or platelets 50 000-100 000/l reduce the dose 75% Recommended by. If the number of granulocytes <500/l or platelets <50 000/l, delaying the introduction of the drug.

To identify hematological toxicity should be a regular examination of the patient and monitor liver and kidney function. Depending on the degree of toxicity the dose can be reduced in each cycle, or begin a new cycle of steps. The decision to postpone the next administration should be based on clinical evaluation of the dynamics of the toxicity of a doctor.

In Patients with liver failure or impaired renal function Gemcitabine should be used with caution, since no studies have been conducted on the use of the drug in patients of these groups.

In patients with mild or moderate renal impairment (CC 30-80 ml / min) no noticeable deviations were observed in the pharmacokinetics of gemcitabine when using the drug.

In patients aged 65 years correction dose is not required.

Use of gemcitabine in children It has not been studied.

Rules of drug infusion solution

To prepare Cytogem solution, use only 0.9% sodium chloride solution without preservatives. To dissolve 200 mg of gemcitabine is added to the vial at least 5 ml of solvent and shake until the lyophilisate is completely dissolved. The maximum concentration of gemcitabine should not exceed 40 mg / ml. In solutions with gemcitabine concentrations greater than 40 mg/ml possible incomplete dissolution.

The prepared solution, containing the required dose of the drug, before administration, dilute with sufficient amount 0.9% sodium chloride solution for intravenous infusion for 30 m. Before administration, you should ensure that there are no suspended particles in the solution..

Side effect

From the hematopoietic system: leukopenia, thrombocytopenia, anemia.

From the digestive system: nausea, vomiting, constipation or diarrhea, stomatitis, giperʙiliruʙinemija, increased activity of liver transaminases and alkaline phosphatase levels.

From the central and peripheral nervous system: headache, drowsiness, sleep disorders, paresthesia.

The respiratory system: breathlessness, cough, rhinitis; rarely – bronchospasm, interstitial pneumonia, pulmonary edema, respiratory distress syndrome (if this occurs, treatment should be discontinued).

Cardio-vascular system: decrease in blood pressure, myocardial infarction, heart failure, arrhythmia.

From the urinary system: proteinuria, hematuria; rarely – hemolytic uremic syndrome.

Dermatological reactions: skin rashes, itching, alopecia.

Allergic reactions: rarely – anaphylactic reactions.

Other: often – flu-like symptoms, peripheral edema, fever, chills, asthenia, back pain, myalgia, swelling of the face.

Contraindications

- Pregnancy;

- Breastfeeding;

- Hypersensitivity to the drug.

FROM caution the drug should be used if liver and/or kidney function is impaired, suppression of bone marrow hematopoiesis (incl. with concurrent radiation or chemotherapy), simultaneous radiation therapy, acute infectious diseases viral, fungal or bacterial origin (incl. enable vetryanaya, shingles).

Pregnancy and lactation

Do not use this drug during pregnancy and breastfeeding.

Cautions

Treatment with gemcitabine should only be carried out under medical supervision, having experience of anticancer therapy.

Platelet counts should be monitored before each gemcitabine administration., white blood cells and granulocytes in their blood. If there are signs of bone marrow suppression, treatment should be suspended or the dose of the drug should be adjusted..

Liver and kidney function should be assessed periodically. Increasing the duration of infusion and frequency of administration leads to increased toxicity.

Administration of gemcitabine for liver metastases, history of hepatitis and alcoholism, and also with cirrhosis of the liver increases the risk of developing liver failure. Treatment with gemcitabine should be discontinued when the first clinical signs of hemolytic uremic syndrome occur..

Patients with lung cancer or lung metastases have an increased risk of respiratory side effects. At the first sign of pneumonitis or the appearance of infiltrates in the lungs, treatment with gemcitabine should be discontinued..

Gemcitabine should be administered after resolution of acute radiation reactions or not before., than 7 days after the end of radiation therapy.

Women and men during gemcitabine therapy and, least, during 6 months after, reliable methods of contraception should be used.

Effects on ability to drive vehicles and management mechanisms

During treatment with gemcitabine, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities., require high concentration and speed of psychomotor reactions.

Overdose

Symptoms: increase in known side effects.

Treatment: if an overdose is suspected, the patient should be placed under constant medical supervision, including careful monitoring of blood counts. If necessary, – symptomatic treatment. Antidote unknown.

Drug Interactions

Gemcitabine has a radiosensitizing effect, therefore, when using the drug during radiation therapy, increased radiation reactions can be expected.

Reduces antibody production and increases side effects when inactivated or live vaccines are administered concomitantly (the interval between the use of drugs should be from 3 to 12 months).

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dry, dark place at a temperature no higher than 25 ° C. Shelf life – 2 year.

The prepared solution can be stored at room temperature from 15° to 30°C for 24 no; should not be frozen to avoid crystallization.