Gemcitover, vial, 1g

Composition

Active ingredient:

gemcitabine hydrochloride in terms of gemcitabine-1000 mg

Auxiliary substances:

mannitol,

sodium acetate,

sodium hydroxide (sodium hydroxide) or hydrochloric acid 1 M

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 incorporated 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

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

Contraindications

Hypersensitivity to gemcitabine.

Side effects

From the hematopoietic organs: often-leukopenia, neutropenia, thrombocytopenia, anemia; very rarely-thrombocytosis.

From the digestive system: very often-nausea, vomiting, increased activity of hepatic transaminases, alkaline phosphatase; often – anorexia, diarrhea, constipation, stomatitis, hyperbilirubinemia.

From the urinary system: very often – proteinuria and hematuria; rarely-hemolytic-uremic syndrome and / or renal failure.

From the skin and skin appendages: often-skin rashes, pruritus, alopecia.

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

From the cardiovascular system: rarely-low blood pressure, myocardial infarction, heart failure, arrhythmia.

From the nervous system: often-headache, drowsiness, insomnia, paresthesia.

Allergic reactions: very rarely-anaphylactic reactions.

Others: very often – flu-like syndrome, peripheral edema; often-fever, chills, asthenia, back pain, myalgia; sometimes-puffiness of the face.

Interaction

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

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

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

How to take, course of use and dosage

Gemcitover is administered intravenously by drip for 30 minutes.

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

Monotherapy.

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

 Combination therapy.

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 on the background of hyperhydration. Breast cancer (locally advanced or disseminated)

Monotherapy.

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

Combination therapy.

As a first-line therapy, with the progression of neoadjuvant therapy, with the inclusion of anthracyclines. The recommended dose of the drug 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 use on day 1 of each 21-day cycle.

Bladder cancer (locally advanced, disseminated, or superficial)

Monotherapy.

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

Intravesical chemotherapy. The recommended dose of the drug is 2000 mg. To obtain a solution for installations, 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 of the drug is 60 minutes. It is administered once a week for 6 weeks. The concentration of the solution should not exceed 40 mg / ml. Epithelial ovarian cancer (locally advanced or disseminated).

Monotherapy.

The recommended dose of the 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 advanced or disseminated).

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

Cervical cancer (locally advanced or disseminated).

Combination therapy.

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

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

In case of development of hematological toxicity, the dose of gemcitabine may be reduced, or its use postponed in accordance with the following scheme: :

Absolute number of granulocytes (in 1 µl)Platelet count (in 1 µl)% of the previous dose> 1000 and>> 100000100500-1000 or 50000-10000075>>< 500 or< 50000 Postpone use

To detect non-hematological toxicity, it is necessary to conduct a regular examination of the patient and monitor liver and kidney functions. Depending on the degree of toxicity, the dose can be reduced during each cycle or with the start of a new cycle in stages.

The decision to postpone the next use of the drug should be based on the doctor’s clinical assessment of the dynamics of toxicity.

Special patient groups

Elderly patients: There is no evidence to suggest that dose adjustment is necessary in elderly patients, although gemcitabine clearance and half-life change with age.

Patients with impaired liver and kidney function: gemcitabine should be used with caution in patients with hepatic insufficiency or impaired renal function, since there are no sufficient data on the use of the drug in this category of patients. Mild or moderate renal insufficiency (creatinine clearance from 30 ml / min to 80 ml / min) does not significantly affect the pharmacokinetics of gemcitabine.

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

Overdose

Symptoms: myelosuppression, paresthesia, severe skin rash.

Treatment: there is no specific antidote. If an overdose is suspected, the patient should be under constant medical supervision, including counting the blood formula; if necessary, symptomatic treatment is carried out.

Special instructions

Gemcitover treatment can only be performed under the supervision of a doctor who has experience in the use of antitumor chemotherapy. Before each use of the drug, it is necessary to monitor the number of platelets, white blood cells and neutrophils in the blood. If there are signs of bone marrow suppression, treatment should be suspended or the dose adjusted. Kidney and liver function should be evaluated periodically.

An increase in the duration of the infusion and the frequency of infusions leads to an increase in toxicity. The use of gemcitabine in patients with liver metastases, hepatitis and alcoholism in the anamnesis, as well as in patients with cirrhosis of the liver increases the risk of developing liver failure. If the first signs of hemolytic-uremic syndrome occur, gemcitabine treatment should be discontinued. Patients with lung cancer or lung metastases have an increased risk of side effects from the respiratory system. Gemcitabine treatment should be discontinued when the first signs of pneumonitis or infiltrates appear in the lungs.

Gemcitabine can be started after acute radiation reactions have resolved or no earlier than 7 days after the end of radiation therapy.Women and men should use reliable methods of contraception during gemcitabine treatment and for at least 6 months thereafter. During treatment, caution should be exercised when driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Lyophilizate for infusion solution preparation

Storage conditions

Store in a dry place, protected from light, at a temperature of 15-30 °C

Shelf life

2 years

Active ingredient

Gemcitabine

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as directed by your doctor

Indications

Cancer