Gemcitover (Lyophilisate) Instructions for Use

ATC Code

L01BC05 (Gemcitabine)

Active Substance

Gemcitabine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antitumor drug. Antimetabolite

Pharmacotherapeutic Group

Antineoplastic agents; antimetabolites; pyrimidine analogues

Pharmacological Action

Antineoplastic agent. It has a cytostatic effect, which is associated with the inhibition of DNA synthesis. In the cell, it is metabolized to active diphosphate and triphosphate nucleosides.

Diphosphate nucleosides inhibit the action of ribonucleotide reductase, which is involved in the production of deoxynucleoside triphosphates necessary for DNA synthesis in the cell, leading to a decrease in their concentration in the cell.

Triphosphate nucleosides actively compete for incorporation into the DNA chain and can also be incorporated into RNA.

After the incorporation of intracellular gemcitabine metabolites 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.

Pharmacokinetics

After IV infusion of gemcitabine at doses of 500-2592 mg/m² over 0.4-1.2 hours, the C_max in plasma was 3.2-45.5 µg/ml and was determined within 5 minutes after the end of the infusion.

The V_d in the central compartment is 12.4 L/m² in women and 17.5 L/m² in men (individual variation – 91.9%). The V_d in the peripheral compartment is 47.4 L/m² and does not depend on gender. Protein binding is practically absent.

Systemic clearance varies from 29.2 L/h/m² to 92.2 L/h/m². Clearance in women is approximately 25% lower than in men. Less than 10% is excreted unchanged in the urine. Renal clearance is 2-7 L/h/m². T_1/2 depends on age and gender and is 42-94 minutes. When administered once a week, Gemcitabine does not accumulate.

Gemcitabine is rapidly metabolized by cytidine deaminase in the liver, kidneys, blood, and other tissues. During the intracellular metabolism of the active substance, mono-, di-, and triphosphates of gemcitabine are formed, which have pharmacological activity. These metabolites are not detected in plasma or urine.

The main metabolite, 2-deoxy-2,2-difluorouridine, has no pharmacological activity and is detected in plasma and urine.

Indications

Non-small cell lung cancer (stages IIIa-IV); advanced carcinomas of the pancreas.

ICD codes

Dosage Regimen

Administer the lyophilisate as an intravenous infusion. Determine the dose individually based on the specific indication, disease stage, hematological status, and the chosen anticancer therapy protocol.

For non-small cell lung cancer, the standard monotherapy regimen is 1000 mg/m². Administer the infusion over 30 minutes once weekly for up to seven weeks, followed by a one-week rest period. For subsequent cycles, administer once weekly for three consecutive weeks, followed by a one-week rest period.

For advanced pancreatic carcinoma, the standard monotherapy regimen is 1000 mg/m². Administer the infusion over 30 minutes once weekly for up to seven weeks, followed by a one-week rest period. For subsequent cycles, administer once weekly for three consecutive weeks, followed by a one-week rest period.

Precede each dose with a complete blood count. Adjust the dosage based on the degree of hematological toxicity. For subsequent cycles, do not administer until the absolute granulocyte count recovers to at least 1000/µL and the platelet count recovers to at least 100,000/µL.

Reduce the dose for patients who experience severe non-hematological toxicity, excluding nausea and vomiting. Permanently discontinue the drug for any unexplained dyspnea, evidence of severe pulmonary toxicity, or hemolytic-uremic syndrome.

Reconstitute the lyophilisate with 0.9% Sodium Chloride Injection without preservatives. Do not use other solutions. The final concentration for administration should not exceed 40 mg/mL. Further dilute the reconstituted solution with 0.9% Sodium Chloride Injection to a total volume of 100-500 mL. Administer the prepared solution within 24 hours when stored at 2-8°C (36-46°F). Do not refrigerate the final solution; administer immediately after preparation.

Adverse Reactions

From the hematopoietic system: leukopenia, thrombocytopenia, anemia.

From the digestive system: nausea, vomiting, diarrhea; rarely – constipation.

From the urinary system: proteinuria, hematuria; rarely – peripheral edema; in isolated cases – renal failure.

Dermatological reactions: skin rash, itching, alopecia, stomatitis; rarely – desquamation, vesicular rash, eczema.

From laboratory parameters: transient increase in the activity of hepatic transaminases, alkaline phosphatase, increase in plasma bilirubin concentration.

From the respiratory system: rarely – bronchospasm, dyspnea.

From the CNS and peripheral nervous system: rarely – drowsiness, weakness, paresthesia.

From the cardiovascular system: rarely – arterial hypotension, pulmonary edema; in isolated cases – myocardial infarction, arrhythmias.

Other: flu-like syndrome.

Contraindications

Hypersensitivity to gemcitabine.

Use in Pregnancy and Lactation

The safety of gemcitabine in human pregnancy has not been studied.

Experimental studies have shown that Gemcitabine has embryo- and fetotoxic effects, negatively affects the course of pregnancy and postnatal development.

The use of gemcitabine during pregnancy should be avoided. Women of childbearing potential must use reliable methods of contraception during treatment.

If it is necessary to use during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Use with caution in cases of impaired liver function, with periodic monitoring of its functional state.

Use in Renal Impairment

Use with caution in cases of impaired renal function, with periodic monitoring of their functional state.

Pediatric Use

The safety and efficacy of gemcitabine in children have not been studied.

Special Precautions

It has some activity in advanced stages of breast cancer, ovarian cancer, kidney cancer, bladder cancer, and prostate cancer, as well as small cell lung cancer.

Use with caution in cases of impaired hematopoiesis; impaired liver and/or kidney function. During treatment, peripheral blood counts should be monitored regularly. If a toxic hematological effect develops, dose regimen adjustment is required depending on the degree of leukopenia and thrombocytopenia.

The safety and efficacy of gemcitabine in children have not been studied.

Effect on ability to drive vehicles and operate machinery

During treatment, one should refrain from potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Drug Interactions

The risk of development and severity of leukopenia and thrombocytopenia increases after prior therapy with cytostatics.

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.