Gemcitover, 1 g

Antitumor agent.

It has cytostatic action which is connected 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 incorporated into RNA.

After intracellular gemcitabine metabolites are incorporated into the DNA chain, one additional nucleotide is added to its growing strands, resulting in complete inhibition of further DNA synthesis and programmed cell death.

Indications

Non-small cell lung cancer (stages IIIa-IV); advanced pancreatic carcinomas.

Active ingredient

Composition

Active substance:

gemcitabine hydrochloride in terms of gemcitabine – 1000 mg

Auxiliary substances:

Mannitol,

Sodium acetate,

sodium hydroxide (caustic soda) or hydrochloric acid 1 M

How to take, the dosage

Hemcitover is given as an intravenous drip for 30 minutes.

Non-small cell lung cancer (locally advanced or disseminated)

Monotherapy.

The recommended dose of drug is 1000 mg/m2 once weekly for 3 weeks, followed by a one-week break, every 28 days.

Combination therapy.

The recommended dose of 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 on a background of hyperhydration.
Breast cancer (locally disseminated or disseminated)

Monotherapy.

If disease progresses after first-line therapy with or without anthracyclines (if anthracyclines are contraindicated), the recommended dose of drug is 1000-1200 mg/m2 on days 1, 8, and 15 every 28 days.

Combination therapy.

As first-line therapy, if neoadjuvant therapy has progressed, with inclusion of anthracyclines. The recommended dose is 1250 mg/m2 on days 1 and 8 in combination with paclitaxel at a dose of 175 mg/m2 approximately 3 hours after gemcitabine on day 1 of each 21-day cycle.

Bladder bladder cancer (locally disseminated, disseminated or superficial)

Monotherapy.

The recommended dose of drug is 1250 mg/m2 on days 1, 8, and 15 every 28 days.

Combination therapy.

The recommended dose of drug is 1000 mg/m2- on days 1, 8, and 15 combined with cisplatin, which is administered at a dose of 70 mg/m2 immediately after the gemcitabine infusion on day 1 or day 2 of each 28-day cycle.

Intravesical chemotherapy.The recommended dose of the drug is 2000 mg. To obtain a solution for injection the drug is dissolved in 100 or 50 ml of 0.9% sodium chloride solution to a concentration of 20 to 40 mg/ml. The exposure time of the drug is 60 minutes. The drug is administered once a week for 6 weeks. The concentration of the solution should not exceed 40 mg/ml.
Epithelial ovarian cancer (locally disseminated or disseminated).

Monotherapy.

The recommended dose of drug is 800-1250 mg/m2 on days 1, 8, and 15 every 28 days.

Combination therapy.

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

Pancreatic cancer (locally disseminated or disseminated).

Monotherapy.
The recommended dose of drug is 1000 mg/m2 once weekly for 7 weeks, followed by a one-week break. Subsequent cycles should consist of infusions given once weekly for 3 weeks, followed by a one-week break.

Cervical cancer (locally disseminated or disseminated).

Combination therapy.

In locally advanced cancer on sequential chemoradiotherapy (neoadjuvant) and in disseminated cancer, gemcitabine is given at a dose of 1250 mg/m2 on days 1 and 8 of a 21-day cycle. Cisplatin is administered after gemcitabine at a dose of 70 mg/m2 on day 1 of the cycle every 21 days on a background of hyperhydration.

In locally advanced cancer with concomitant chemoradiotherapy, gemcitabine is given at a dose of 125 mg/m2 once a week 1-2 hours before radiation therapy, followed (immediately after gemcitabine administration) by cisplatin at a dose of 40 mg/m2.

If hematologic toxicity develops, the dose of gemcitabine may be reduced or delayed according to the following regimen:

The absolute number of granulocytes (in 1 μL)The number of platelets (in 1 μL)% of the previous dose> 1000and> 100000100500-1000 or50000-10000075< 500 or< 50000Delay administration

The patient should be evaluated regularly and liver and kidney function should be monitored to detect non-hematologic toxicity. Depending on the degree of toxicity, the dose can be reduced during each cycle or in steps with the start of a new cycle.

The decision to delay the next administration of the drug should be based on the clinician’s clinical assessment of the toxicity trend.

Special patient groups

Elderly patients:There is no evidence to suggest that the dose should be adjusted in elderly patients, although gemcitabine clearance and half-life do change with age.

Patients with impaired hepatic and renal function:Gemcitabine should be used with caution in patients with hepatic impairment or impaired renal function, as there are insufficient data on the use of the drug in this patient population. Mild to moderate renal insufficiency (creatinine clearance from 30 ml/min to 80 ml/min) has no appreciable effect on the pharmacokinetics of gemcitabine.

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

Interaction

Gemcitover has a radiosensitizing effect, so when using the drug against the background of radiation therapy you can expect increased radiation reactions.

Decreases the production of antibodies and increases the side effects with the simultaneous use of inactivated or live viral vaccines (the interval between the use of medicines should be from 3 to 12 months).

Immunosuppressants (azathioprine, chlorambucil, glucocorticosteroids, cyclophosphamide, cyclosporine, mercaptopurine) increase the risk of infections.

Special Instructions

Treatment with Gemcitover should only be carried out under the supervision of a physician experienced in the use of antitumor chemotherapy. Before each injection of the drug it is necessary to monitor the number of platelets, leukocytes and neutrophils in the blood. In case of signs of inhibition of bone marrow function, it is necessary to suspend treatment or adjust the dose. Periodic assessment of renal and hepatic function should be carried out.

Lengthening the duration of infusion and the frequency of infusions leads to increased toxicity. Administration of gemcitabine for liver metastases, history of hepatitis and alcoholism, and cirrhosis increases the risk of hepatic failure. If the first signs of hemolytic-uremic syndrome occur, treatment with gemcitabine should be discontinued. Patients with lung cancer or lung metastases have an increased risk of respiratory side effects. If the first signs of pneumonitis or lung infiltrates appear, treatment with gemcitabine should be stopped.

Gemcitabine may be started after acute radiation reactions have resolved or no earlier than 7 days after completion of radiation therapy. Women and men should use reliable contraceptive methods during treatment with gemcitabine and for at least 6 months after. During treatment, caution should be exercised while driving motor transport and engaging in potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

Hypersensitivity to gemcitabine.

Side effects

Blood organs: often – leukopenia, neutropenia, thrombocytopenia, anemia; very rarely – thrombocytosis.

In the digestive system: very often – nausea, vomiting, increased liver transaminase activity, alkaline phosphatase; frequently – anorexia, diarrhea, constipation, stomatitis, hyperbilirubinemia.

Urinary system: very common – proteinuria and hematuria; rarely – hemolytic-uremic syndrome and/or renal failure.

Skin and skin appendages: often – skin rash, itching, alopecia.

Respiratory system: very common – shortness of breath; common – cough, rhinitis; sometimes – bronchospasm, interstitial pneumonia, pulmonary edema; rarely – acute respiratory distress syndrome (if these symptoms occur, treatment should be discontinued).

Cardiovascular system disorders: rare – decreased blood pressure, myocardial infarction, heart failure, arrhythmia.

Nervous system disorders: often – headache, somnolence, insomnia, paresthesias.

Allergic reactions: very rare – anaphylactic reactions.

Others: very often – flu-like syndrome, peripheral edema; often – increase of body temperature, chills, asthenia, back pain, myalgia; sometimes – facial edema.

Overdose

Symptoms: myelosuppression, paresthesias, pronounced skin rash.

Treatment: there is no specific antidote. If overdose is suspected, the patient should be under constant medical supervision, including blood counts; if necessary, symptomatic treatment is administered.

Similarities