Ongecin (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 agent, antimetabolite

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 mcg/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 pancreatic carcinoma.

ICD codes

Dosage Regimen

Establish the dosage individually based on the specific indication, disease stage, hematological status, and the chosen anticancer therapy protocol.

For non-small cell lung cancer, administer 1000 mg/m² intravenously. Infuse over 30 minutes. Use this dose on days 1, 8, and 15 of each 28-day cycle. Combine with a platinum agent like cisplatin.

For advanced pancreatic carcinoma, administer 1000 mg/m² intravenously. Infuse over 30 minutes. Use this dose on days 1, 8, and 15 of a 28-day cycle. This can be used as a single agent or in combination therapy.

Prior to each administration, monitor complete blood count (CBC) including platelets. Adjust the dose based on the degree of myelosuppression.

For subsequent cycles, delay dosing until the absolute neutrophil count (ANC) recovers to at least 1500 x 10⁶/L and platelet count recovers to at least 100,000 x 10⁶/L.

Reduce the dose for 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 diluents. The final concentration should not exceed 40 mg/mL. Further dilute the reconstituted solution in 0.9% Sodium Chloride Injection to a final volume of 100-500 mL for infusion.

Inspect the solution visually for particulate matter and discoloration before administration. Discard if present. Administer the diluted solution within 24 hours of reconstitution when stored at 2-8°C (36-46°F). Do not refrigerate the final infusion solution; administer it at room temperature.

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 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 hematopoietic disorders; 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 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 2°C (36°F) to 30°C (86°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.