Gemcitabine (Lyophilisate, Concentrate) 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 strands, 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 at 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 pancreatic carcinoma.

ICD codes

Dosage Regimen

Administer gemcitabine intravenously only after reconstitution and dilution. Determine the dosage individually based on body surface area, indication, therapeutic regimen, and hematological tolerance.

For non-small cell lung cancer, use a dose of 1000 mg/m². Infuse intravenously over 30 minutes. Administer on days 1, 8, and 15 of each 28-day cycle, in combination with cisplatin. Alternatively, administer on days 1, 8, and 15 of each 28-day cycle or on days 1 and 8 of each 21-day cycle as monotherapy.

For advanced pancreatic carcinoma, use a dose of 1000 mg/m². Infuse intravenously over 30 minutes. Administer once weekly for up to 7 weeks, followed by a one-week rest. Subsequent cycles consist of weekly injections for 3 consecutive weeks out of every 4 weeks.

Monitor blood counts prior to each dose. Adjust dosage based on the degree of myelosuppression. For absolute granulocyte count between 500-999 x 10⁶/L and/or platelet count between 50,000-99,999 x 10⁶/L, administer 75% of the full dose. Omit the dose if the absolute granulocyte count is below 500 x 10⁶/L and/or platelet count is below 50,000 x 10⁶/L.

Adjust dosage in patients with renal impairment. For patients with moderate renal impairment (creatinine clearance 30-60 mL/min), reduce the dose as clinically indicated. Do not administer to patients with severe renal impairment (creatinine clearance less than 30 mL/min).

Use caution in elderly patients and those with impaired liver function. No specific dosage recommendation exists for hepatic impairment; base adjustments on clinical assessment and tolerance.

Reconstitute the lyophilisate with 0.9% Sodium Chloride Injection without preservatives. Shake to dissolve. The resulting concentrate contains 38 mg/mL gemcitabine. Further dilute the appropriate volume of this concentrate in 0.9% Sodium Chloride Injection to achieve a final concentration not exceeding 40 mg/mL. Use the prepared solution immediately; stability is limited. Discard any unused portion.

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.

In experimental studies, it has been 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 should 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 case of impaired liver function, with periodic monitoring of its functional state.

Use in Renal Impairment

Use with caution in case 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 case of impaired hematopoiesis; impaired liver and/or kidney function.

During treatment, peripheral blood counts should be regularly monitored. 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 the 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 and severity of leukopenia and thrombocytopenia increase 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.