Gemcivin (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Pharmasintez-Nord, JSC (Russia)

ATC Code

L01BC05 (Gemcitabine)

Active Substance

Gemcitabine (Rec.INN registered by WHO)

Dosage Forms

	Gemcivin	Lyophilisate for preparation of concentrate for solution for infusion 200 mg: vial 1 pc.
		Lyophilisate for preparation of concentrate for solution for infusion 1000 mg: vial 1 pc.
		Lyophilisate for preparation of concentrate for solution for infusion 1400 mg: vial 1 pc.
		Lyophilisate for preparation of concentrate for solution for infusion 1500 mg: vial 1 pc.

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of concentrate for solution for infusion white or almost white in color.

Excipients : mannitol – 200 mg, sodium acetate trihydrate – 12.5 mg, hydrochloric acid – q.s. for pH adjustment to 3.0, sodium hydroxide – q.s. for pH adjustment to 3.0.

200 mg – vials with a capacity from 10 ml to 100 ml (1) – cardboard packs.

Lyophilisate for preparation of concentrate for solution for infusion white or almost white in color.

Excipients : mannitol – 1000 mg, sodium acetate trihydrate – 62.5 mg, hydrochloric acid – q.s. for pH adjustment to 3.0, sodium hydroxide – q.s. for pH adjustment to 3.0.

1000 mg – vials with a capacity from 10 ml to 100 ml (1) – cardboard packs.

Lyophilisate for preparation of concentrate for solution for infusion white or almost white in color.

Excipients : mannitol – 1400 mg, sodium acetate trihydrate – 87.5 mg, hydrochloric acid – q.s. for pH adjustment to 3.0, sodium hydroxide – q.s. for pH adjustment to 3.0.

1400 mg – vials with a capacity from 10 ml to 100 ml (1) – cardboard packs.

Lyophilisate for preparation of concentrate for solution for infusion white or almost white in color.

Excipients : mannitol – 1500 mg, sodium acetate trihydrate – 155.5 mg, hydrochloric acid – q.s. for pH adjustment to 3.0, sodium hydroxide – q.s. for pH adjustment to 3.0.

1500 mg – vials with a capacity from 10 ml to 100 ml (1) – cardboard packs.

Clinical-Pharmacological Group

Antitumor drug. Antimetabolite

Pharmacotherapeutic Group

Antineoplastic agents; antimetabolites; pyrimidine analogues

Pharmacological Action

Antitumor agent. It exerts a cytostatic effect 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.

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, leading 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 possess pharmacological activity. These metabolites are not detected in plasma or urine.

The main metabolite, 2-deoxy-2,2-difluorouridine, lacks 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 gemcitabine as an intravenous infusion. The dosage is established individually based on the specific indication, disease stage, hematological status, and the chosen anticancer therapy regimen.

For non-small cell lung cancer, the monotherapy regimen is 1000 mg/m². Administer the infusion once weekly for up to seven weeks, followed by a one-week rest period. Subsequent cycles consist of weekly administrations for three consecutive weeks, followed by a one-week rest.

For advanced pancreatic carcinoma, the recommended dose is 1000 mg/m². Administer the infusion once weekly for up to seven weeks, followed by a one-week rest period. Subsequent cycles consist of weekly administrations for three consecutive weeks, followed by a one-week rest.

Calculate the dose based on the patient’s body surface area. Reconstitute the lyophilisate strictly according to the manufacturer’s instructions using an appropriate sterile diluent, such as 0.9% sodium chloride solution without preservatives.

After reconstitution, further dilute the concentrate with 0.9% sodium chloride solution to a final concentration typically between 0.1 mg/mL and 40 mg/mL. Administer the prepared solution as a controlled intravenous infusion. The standard infusion time is 30 minutes.

Do not administer as a rapid intravenous bolus injection. Monitor the patient’s peripheral blood cell counts, including platelets, before each planned dose. Adjust or withhold the dose based on the degree of hematological toxicity, following established guidelines for myelosuppression.

Perform regular monitoring of renal and hepatic function during treatment. Dosage adjustments are necessary for patients with significant renal or hepatic impairment. The safety and efficacy in the pediatric population have not been established.

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, ALP, 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 use during lactation is necessary, the issue of discontinuing breastfeeding should be considered.

Use in Hepatic Impairment

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

Use in Renal Impairment

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

Pediatric Use

The safety and efficacy of gemcitabine use 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 patients with hematopoietic disorders; impaired liver and/or kidney function. During treatment, peripheral blood counts should be monitored regularly. If toxic hematological effects develop, dose regimen adjustment is required depending on the degree of leukopenia and thrombocytopenia.

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

Effect on ability to drive vehicles and operate machinery

During treatment, one should refrain from potentially hazardous activities requiring 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 2°C (36°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.