Gemcitabine - Instructions For Use, Reviews, Price, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Gemcitabine

Gemcitabine: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. Drug interactions
12. 12. Analogs
13. 13. Terms and conditions of storage
14. 14. Terms of dispensing from pharmacies
15. 15. Reviews
16. 16. Price in pharmacies

Latin name: Gemcitabin

ATX code: L01BC05

Active substance: gemcitabine

Manufacturer: Nativa LLC (Russia); Hetero Labs Limited (India); OAO Nizhpharm (Russia); VMJ Pharmaceuticals Pvt. Ltd. (VMG Pharmaceuticals Pvt. Ltd.) (India)

Description and photo update: 2019-07-10

Prices in pharmacies: from 971 rubles.

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Gemcitabine is an antimetabolite, anticancer drug.

Release form and composition

The dosage form of Gemcitabine is a lyophilisate for preparing a solution for infusion: a white powdery mass (200 mg or 1000 mg in a glass bottle without color, in a cardboard box 1, 5, 10, 48, 50, 100, 150, 200, 250 or 300 vials).

1 bottle contains:

• active substance: gemcitabine hydrochloride - 228 mg or 1140 mg, which is equivalent to 200 mg or 1000 mg of gemcitabine;
• auxiliary components: sodium acetate trihydrate, mannitol, sodium hydroxide.

Pharmacological properties

Pharmacodynamics

Gemcitabine is a pyrimidine analogue and belongs to prodrugs. In the body, it becomes active through participation in metabolic processes in the tumor cell under the influence of nucleoside kinases, and forming pharmacologically active diphosphate and triphosphate nucleosides. Gemcitabine diphosphate is a ribonucleotide reductase inhibitor; gemcitabine triphosphate is incorporated into deoxyribonucleic acid (DNA), to ribonucleic acid (RNA) this applies to a lesser extent, adding one additional nucleotide to its growing chains, prevents further DNA synthesis and stops programmed cell lysis (apoptosis). In this case, DNA repair is not feasible. With the participation of gemcitabine in T-lymphoblastic cells, the process of inducing internucleosomal DNA fragmentation occurs,which refers to the factors that program cell death.

Gemcitabine is characterized by phase specificity of action: it stops the vital activity of cells in the S-phase and prevents the tumor progression of cells, which is observed at the border of the S and G ₁ phases. Gemcitabine has significant radiosensitizing properties, which are manifested at lower concentrations than cytotoxic ones.

Pharmacokinetics

After a single infusion of gemcitabine at a dose of 1000 mg / m ² for 30 minutes, its maximum plasma concentration is reached in about 3–15 minutes. It binds to plasma proteins slightly (the degree of binding does not exceed 10%). The therapeutic concentration of nucleosides in blood plasma is 4–5 μg / ml and remains constant for 1.5 hours. Systemic clearance, volume of distribution, and elimination half-life tend to be linear with patient age and duration of infusion.

With intravenous infusion in doses Gemcitabine 500-2592 mg / m ² over 0.4-1.2 hours its maximum concentration in the plasma is from 3.2 to 45.5 ug / ml was determined for 5 minutes at the end of infusion. The volume of distribution in the central part is equal to 12.4 l / m ² for women and 17.5 l / m ² for men (figure individual differences reaches 91.9%). The volume of distribution in the peripheral part is 47.4 l / m ² and does not depend on the patient's gender.

In women, the half-life is longer than in men, amounting to 49-94 minutes and 42-79 minutes, respectively. Systemic clearance varies from 0.5 to 1.5 l / min / m ². In women, there is a lower (approximately 25%) drug clearance compared to male patients. The half-life of the active metabolite from peripheral blood mononuclear cells in the terminal phase ranges from 1.7 to 19.4 hours. Renal clearance ranges from 2 to 7 l / h / m ². When administered once a week, gemcitabine does not accumulate in the body.

The drug is gradually metabolized in blood cells, kidneys, liver with the help of the enzyme cytidine deaminase, forming an inactive metabolite 2'-deoxy-2 ', 2'-difluoruridine (uracil). The maximum blood level of this metabolite is recorded 30 minutes after infusion. The concentration of nucleosides inside cells is directly proportional to the concentration in plasma, however, if their concentration in blood plasma exceeds 5 μg / ml, no further increase in the intracellular concentration of nucleosides is observed.

Gemcitabine is excreted mainly in the urine as a metabolite of uracil, which has no pharmacological activity (89% of the dose taken), and also unchanged (about 10% of the dose taken). Less than 1% of the dose taken is excreted through the intestines.

Renal failure of moderate or moderate severity (glomerular filtration rate is 30-80 ml / min) does not noticeably change the pharmacokinetic parameters of gemcitabine. In patients with reduced renal function, the inactive metabolite can accumulate in the body.

Indications for use

According to the instructions, Gemcitabine is indicated for the treatment of locally advanced or metastatic tumors:

• non-small cell lung cancer: monotherapy - elderly patients with the second functional status on the ECOG-WHO scale (five-point system for assessing the general condition of a cancer patient 0-4), or first-line therapy - in combination with cisplatin;
• urothelial cancer (cancer of the urethra, ureters, renal pelvis, bladder): monotherapy or in combination with cisplatin;
• breast cancer: monotherapy - with the progression of the condition after first-line therapy in combination with anthracyclines, or combination therapy with paclitaxel after preliminary use of anthracyclines in neoadjuvant and / or adjuvant therapy in patients with no contraindications to their appointment;
• ovarian cancer: monotherapy or in combination with carboplatin in the progression of pathology in patients who have undergone the first line of therapy based on platinum compounds;
• cervical cancer: in combination with cisplatin;
• monotherapy for pancreatic cancer.

Contraindications

• period of pregnancy;
• breast-feeding;
• childhood;
• hypersensitivity to the components of the drug.

Care should be taken when using Gemcitabine in patients with acute forms of infectious diseases of viral, fungal or bacterial etiology (including shingles, chickenpox), liver failure, metastatic liver damage, hepatitis, a history of cardiovascular pathologies, inhibition of bone marrow hematopoiesis (including after radiation or chemotherapy), severe renal failure, chronic alcoholism and during the period of radiation therapy.

Instructions for the use of Gemcitabine: method and dosage

The ready-made solution of Gemcitabine is used by intravenous (iv) drip for 0.5 hours.

Treatment should take place in a hospital with the obligatory observance of the established rules for dilution and preparation of injection solutions (sterile box, disposable surgical gloves, mask) by specially trained medical personnel.

To dissolve the lyophilisate, you can use only 0.9% sodium chloride solution for injection, which does not contain preservatives.

To the contents of the vial, add the amount of solvent per 200 mg of gemcitabine at least 5 ml of liquid, since the concentration of the active substance should not exceed 40 mg per 1 ml. For complete dissolution of the drug, the bottle must be gently shaken until it acquires a transparent structure.

After dissolving the required dose of the lyophilisate, the prepared solution is mixed with a sufficient amount of solvent for intravenous infusion.

Before direct administration, a visual assessment of the solution for the absence of suspended particles is required.

Recommended dosage:

• non-small cell lung cancer: monotherapy - at the rate of 1000 mg per 1 m ² of body surface on the 1st, 8th and 15th days of each 28-day cycle; as part of a combination therapy with cisplatin: 1250 mg per 1 m ² on the 1st and 8th days of each 21-day cycle or 1000 mg per 1 m ² on the 1st, 8th and 15th days of each 28-day cycle (dose of cisplatin - 70 mg per 1 m ² on the 1st day of the cycle after drug administration against the background of overhydration);
• urothelial cancer (including superficial): monotherapy - 1250 mg per 1 m ² on the 1st, 8th and 15th days of each 28-day cycle; combination therapy with cisplatin - 1000 mg per 1 m ² on the 1st, 8th and 15th days of each 28-day cycle. Cisplatin (immediately after the infusion of gemcitabine) - at a dose of 70 mg per 1 m ² on the 1st or 2nd day of each cycle;
• breast cancer: monotherapy for the progression of the neoplasm after the first line of therapy, including anthracyclines - 1000–1200 mg per 1 m ² on the 1st, 8th and 15th days of each 28-day cycle. Combined first-line therapy in the progression of the condition after anthracyclines including neoadjuvant and / or adjuvant therapy - 1250 mg per 1 m2 ^of body surface on the 1st and 8th days of the 21-day cycle in combination with paclitaxel (at a dose of 175 mg per 1 m ² on the 1st day of each cycle for three hours intravenous drip prior to drug administration);
• ovarian cancer: monotherapy - 800-1250 mg per 1 m ² on the 1st, 8th and 15th days of each 28-day cycle; combination therapy - 1000 mg per 1 m ² on the 1st and 8th days of each 21-day cycle in combination with carboplatin at a dose of 4 mg per 1 ml per minute (on the 1st day of each cycle after infusion gemcitabine);
• cervical cancer: combination therapy - 1250 mg per 1 m ² on the 1st and 8th days of a 21-day cycle in combination with cisplatin at a dose of 70 mg per 1 m ² on the 1st day of the cycle after drug administration in the background hyperhydration. With simultaneous chemoradiation therapy of locally advanced cancer, gemcitabine is infused 1–2 hours before the start of radiation therapy at a dose of 125 mg per 1 m ², followed by intravenous administration of cisplatin at a dose of 40 mg per 1 m ²;
• pancreatic cancer: monotherapy - 1000 mg per 1 m ² once a week. The duration of the course is 7 infusions, then after a week's break, the dose of the drug is administered on the 1st, 8th and 15th days of each 28-day cycle.

The general scheme of administration for all indications with a 28-day cycle: infusion at the recommended dose is carried out 1 time per week for 3 weeks, followed by a 1 week break and the cycle is repeated.

During therapy, the dose of Gemcitabine can be reduced by 50% with the development of a severe form (grade 3-4) of non-hematological toxicity (with the exception of nausea, vomiting, alopecia).

Before each procedure for administering the drug, the patient should check the level of concentration of leukocytes, platelets and granulocytes. In the case of symptoms indicating bone marrow suppression, treatment is temporarily stopped or continued at a reduced dose.

When treating non-small cell lung cancer, urothelial cancer (monotherapy or in combination with cisplatin), pancreatic cancer with a total granulocyte count of 1000x10 ⁶ / l, the recommended dose is not changed, at 500-999x10 ⁶ / l it is reduced by 25%, and with a less than 500x10 ⁶ / l, the use of Gemcitabine is temporarily stopped.

When combined therapy of breast cancer with paclitaxel, the dose of the drug is adjusted taking into account the indicator of the total number of granulocytes and platelets. If the total number of granulocytes is higher than 1200x10 ⁶ / l, the dose is not changed, if this indicator is in the range 1000-1199x10 ⁶ / l, the dose is reduced by 25%, 700-999x10 ⁶ / l (and the number of platelets is equal to or higher than 50,000x10 ⁶ / l) - the dose is reduced by 50%, less than 700x10 ⁶ / l - the treatment is temporarily stopped.

When combined therapy of ovarian cancer with carboplatin, the recommended dose of Gemcitabine is not reduced with a total number of granulocytes equal to or higher than 1500x10 ⁶ / l, with an indicator of 1000-1499x10 ⁶ / l, the dose is reduced by 50%, and if less than 1000x10 ⁶ / l, a break is prescribed in treatment.

Patients over the age of 65 years do not require a change in the dosage regimen.

At a glomerular filtration rate of 30–80 ml / min in patients with moderate or moderate renal failure, the pharmacokinetics of gemcitabine does not change significantly.

After the procedure, it is necessary to dispose of needles, syringes, vials and the rest of the unused drug.

Side effects

• from the hematopoietic system: often - anemia, leukopenia, thrombocytopenia; very rarely - thrombocytosis;
• from the cardiovascular system: rarely - a decrease in blood pressure (BP), myocardial infarction, chest pain, arrhythmia, heart failure;
• from the central nervous system: often - insomnia, headache, drowsiness;
• from the digestive system: very often - nausea, vomiting, increased activity of liver enzymes, alkaline phosphatase; often - diarrhea, anorexia, stomatitis, constipation, increased bilirubin levels;
• on the part of the skin: often - skin rash, alopecia, itching;
• from the respiratory system: very often - shortness of breath; often - rhinitis, cough; infrequently - pulmonary edema, interstitial pneumonia, bronchospasm; rarely - an acute form of respiratory distress syndrome;
• from the urinary system: very often - hematuria and moderate proteinuria; rarely - renal failure, symptoms of hemolytic uremic syndrome (thrombocytopenia, decreased hemoglobin concentration, increased levels of creatinine, bilirubin, lactate dehydrogenase and / or urea in serum);
• local reactions: infrequently - redness, pain or irritation at the injection site;
• others: very often - peripheral edema, flu-like syndrome; often - chills, fever, asthenia, myalgia, back pain; infrequently - puffiness of the face, paresthesia, violation of tendon reflexes; very rarely - anaphylactic reactions.

Overdose

When taking Gemcitabine in high doses, an overdose of the drug is accompanied by the following symptoms: pronounced skin rashes, manifestations of anemia and myelodepression (increased weakness or fatigue), paresthesia, neutropenia, leukopenia, thrombocytopenia (ecchymosis, hemorrhage, bleeding, blood in feces and urine, tar black), symptoms of infection (painful or difficult urination, cough, chills, back or side pain, hoarseness).

If an overdose is suspected, symptomatic therapy is recommended. You should also ensure constant medical monitoring of the patient's condition, which will include the calculation of the blood formula.

The specific antidote for gemcitabine is unknown.

special instructions

You can start using Gemcitabine if the absolute number of granulocytes is 1500 / μl or more, and the number of platelets is not less than 100,000 / μl.

The decision to cancel the administration of the next dose of the drug is made by the attending physician based on a clinical assessment of the dynamics of toxicity.

For the timely detection of non-hematological toxicity, regular examination of the patient and assessment of renal and liver function is required. Dose reduction is shown during the current cycle or at the beginning of a new cycle, stepwise, taking into account the degree of toxicity.

In case of accidental contact of the drug on the skin or mucous membranes, immediately wash the affected area thoroughly with a strong stream of water or with soap.

The risk of developing side effects of Gemcitabine from the respiratory system in lung cancer or metastases in the lungs is increased.

If symptoms of hemolytic uremic syndrome, pneumonitis, or suspicion of it appear during therapy, the drug should be discontinued immediately.

The frequency and duration of the infusion should not be violated, since with the frequency of administration more than once a week or the administration of Gemcitabine for more than one hour, the risk of adverse effects and an increase in their severity increases.

The frequency and severity of leukopenia or thrombocytopenia increases against the background of previous treatment with cytostatics, and a progressive decrease in the number of leukocytes and platelets can be observed after completion of therapy.

The risk of developing liver failure is increased in patients with liver metastases, liver cirrhosis, hepatitis, or a history of alcoholism.

The patient should be informed of the need for urgent medical attention if symptoms of bone marrow suppression, bleeding of unknown origin or hemorrhage, pinpoint red spots on the skin, black tarry stools, blood in urine or feces appear during the treatment period.

Women and men of childbearing age should use reliable contraception during and for 6 months after discontinuation of therapy.

During the period of using Gemcitabine, any dental interventions and vaccination with viral vaccines are contraindicated.

The use of vaccines is possible only 3–12 months after the end of the use of gemcitabine.

Due to the risk of bleeding, care must be taken when brushing teeth, using toothpicks and floss to avoid damaging the gums.

Influence on the ability to drive vehicles and complex mechanisms

During the period of treatment, care should be taken when driving vehicles and mechanisms.

Application during pregnancy and lactation

The safety of gemcitabine in pregnant women has not been studied. The results of experimental studies indicate that the drug is characterized by fetal and embryotoxic effects, as well as a negative effect on the course of pregnancy and postnatal development of the child. Therefore, the appointment of Gemcitabine during pregnancy is contraindicated.

Women receiving Gemcitabine should stop breastfeeding because of the potential threat to the baby.

Pediatric use

The safety and efficacy of Gemcitabine in children has not been proven.

Drug interactions

With the simultaneous use of Gemcitabine:

• cisplatin causes more frequent manifestations of alopecia, hematological toxicity, gastrointestinal toxicity (stomatitis, nausea, vomiting, diarrhea);
• paclitaxel contributes to increased hematologic toxicity, usually manageable;
• Azathioprine, glucocorticosteroids, chlorambucil, cyclosporine, cyclophosphamide, mercaptopurine (immunosuppressants) increase the risk of infections;
• live viral vaccines can intensify the replication of the vaccine virus and increase side effects;
• inactivated vaccines suppress the production of antiviral antibodies;
• radiation therapy contributes to additive suppression of bone marrow function.

With sequential radiation and chemotherapy, it is recommended to start administering gemcitabine no earlier than one week after acute radiation reactions have passed.

It is strictly forbidden to mix Gemcitabine with other medicines.

Analogs

Analogues of Gemcitabine are: Gemcybin, Gemtaz, Hematix, Gemcitera, Dercin, Oncogem, Tolgecit, Strigem, Cytogem

Terms and conditions of storage

Keep out of the reach of children.

Store at temperatures up to 25 ° C, protected from moisture and light.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews of Gemcitabine

According to reviews, Gemcitabine is considered to be especially effective for bladder cancers. For tumors of this localization, it is used as a monotherapy. In patients with malignant neoplastic formations of other localization, the drug is used as part of a combination treatment (for lung cancer it is combined with Cisplatin, and for pancreatic cancer - with Tarceva). Such treatment regimens are reported to significantly improve patient survival. Since the drug is mainly prescribed in combination with other drugs, it is rather difficult to evaluate separately the effects of this substance on the body. However, the available results of randomized trials indicate that clear differences between the combinations of cisplatin / gemcitabine,cisplatin / paclitaxel or paclitaxel / carboplatin was not detected.

Patients in their reviews most often mention adverse reactions associated with taking Gemcitabine: abdominal pain, diarrhea, intestinal colic, venous thrombosis, stomatitis, deterioration of health, especially with long courses of treatment. According to some patients, treatment with the drug did not give any noticeable results.

Price for Gemcitabine in pharmacies

At the moment, the price of Gemcitabine remains unknown as the drug is not available for sale.

The cost of its analogue Gemcitabine-Medak is 800‒1076 rubles. per bottle 200 mg or 3386‒3399 rubles. per bottle 1000 mg.

Gemcitabine: prices in online pharmacies

Drug name Price Pharmacy

Gemcitabine medak 200 mg lyophilisate for preparation of solution for infusion 1 pc. 971 RUB Buy

Gemcitabine medak 1000 mg lyophilisate for preparation of solution for infusion 1 pc. RUB 3157 Buy

Gemcitabine medak 1500 mg lyophilisate for preparation of solution for infusion 1 pc. RUB 4182 Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!