Gemcitabine: manufacturer, instructions for use, price in Moscow, reviews, analogs

click fraud protection

Gemcitabine, a category of cytostatic antitumor drugs, is a whitish or white substance that is highly soluble in water, moderately in methanol and almost unresolvable in ethanol and organic solvents.

Form release, composition and packaging

Gemcitabine is available in the form of a lyophilized powder and packaged in transparent glass vials( containing 200, 1000 and 1500 mg of the drug), for sealing, bromobutyl rubber plugs of gray color sealed in aluminum caps with tear-off linings are used.

Each bottle is additionally packaged in a cardboard box and put into it instruction for use.

Manufacturer

The production of gemcitabine is established at specialized enterprises:

• The largest in Central and Eastern Europe Croatian pharmaceutical company Pliva.
• of the Austrian company Ebewe Pharma.
• Private German company Medak GmbH.
• of Russian pharmaceutical companies "Nizhpharm OJSC" and "ARS LLC".
• to the Indian pharmaceutical company Hetero Labs Limited.
• of the Belarusian pharmaceutical association "Belmedpreparaty".

Indications for use

Gemcitabine is used to treat patients with cancer:

• pancreas( metastatic or locally advanced adenocarcinoma);
• of the bladder, kidney and prostate( good results are given by a combination of gemcitabine and cisplatin);
• lung( in this case the drug can be used during monotherapy or in combination with cisplatin);
• of the mammary glands( its metastatic inoperable forms, to the aid of gemcitabine in this case comes the antitumor drug paclitaxel);
• of the ovaries( epithelial carcinomas, the drug regimen includes carboplatin);
• of the testicle( refractory).

Contraindications

Acceptance of gemcitabine is strictly prohibited:

• to people who are hypersensitive to the drug;
• to pregnant women;
• to nursing mothers.

Extreme caution in prescribing this medication should be shown with respect to patients:

• having impaired renal and hepatic function;
• suffering from infectious diseases of a bacterial or viral nature;
• with marked inhibition of hematopoiesis by bone marrow cells.

Mechanism of action

Gemcitabine is able to show an active cytotoxic effect on different types of tumor cells, which is characterized by pronounced phase-specificity.

Under its influence, the cancer cells, which are in the so-called S-phase, during which the deoxyribonucleic acid is synthesized, die first.

When creating certain conditions, the drug is able to stop the process of cell division at an earlier stage of G1, which is a transition to the phase of S.

Once in the human body, gemcitabine undergoes a series of chemical changes that result in the formation of special substances - nucleosides. With the help of diphosphate nucleosides, the action of ribonucleotide reductase, a special enzyme, accelerating the reaction ends, resulting in the formation of substances without which DNA synthesis is impossible.

Trisphosphate nucleosides at this time develop the activity necessary to displace deoxynucleoside triphosphates( enzymes that are both energy sources and the building material of cells) and integrate into RNA and DNA molecules. The appearance of additional nucleotides in the DNA chain leads to a complete slowdown in its subsequent synthesis and death of cancer cells.

After the introduction of gemcitabine, its maximum concentration in the blood plasma begins in 5-10 minutes and remains at the level of therapeutic values ​​for an hour and a half.

The association of the preparation with blood plasma proteins remains insignificant( at the level of 10%), so the level of its distribution in the tissues of the organism remains as low as it is.

The half-life of the drug is between thirty and ninety minutes. The main( up to 99%) amount of the drug, converted into an inactive metabolite, is excreted along with the urine, the remainder - with the feces.

If the dosing of the drug is carried out in full compliance with the instruction, its complete excretion is carried out within a time interval of six to ten hours from the time of administration. Gemcitabine, administered no more than once a week, does not have time to accumulate in the tissues of the body.

Instructions for Use Gemcitabine: dosage of

Gemcitabine is intended exclusively for intravenous administration with a dropper.

By performing infusions( the drug is injected drip, the duration of the procedure should be at least half an hour) should be handled only by a qualified specialist who has extensive experience in treating patients with cancer. During the introduction of gemcitabine, you must carefully monitor the patient's condition.

When performing appointments( providing a dosing regimen and duration of the therapeutic course), the attending physician must take into account the type and stage of the malignant neoplasm.

For the infusion, use a fresh solution of the drug, prepared in accordance with all the rules of aseptic in accordance with the following points of the instruction:

• Only physiological solution is suitable for dilution of the lyophilizate( this is called a 0.9% solution of sodium chloride).
• Inside the vial containing 200 mg of lyophilizate, 5 ml of saline is injected;to dilute one gram of the drug will require 25 ml of solvent. The most popular concentration of solution for injection is 40 mg of gemcitabine per 1 ml of saline.
• After completing the saline solution, the vial of the medicine is shaken thoroughly, ensuring complete dissolution of the powder. The color of the freshly prepared solution may turn yellowish.
• The appearance of foreign impurities and the changed color of the solution indicate that the drug is unsuitable for use.

The dosage regimen of gemcitabine in the instructions for use of the drug is described as follows:

• When treating a breast tumor gemcitabine is used in conjunction with a cytostatic drug paclitaxel( duration of the therapeutic course is 21 days).Infusion of gemcitabine is preceded by a three-hour procedure for the drip of an auxiliary preparation. The frequency of such infusions: the first and the eighth day of treatment.
• For the treatment of patients with pancreatic cancer , gemcitabine is administered once a week( 1000 mg per m2) for seven weeks. After this, they hold a week's pause, and then change the treatment schedule, performing infusions for three weeks, alternating treatment with seven-day rest periods.
• Monotherapy of bile duct tumors is carried out by weekly gemcitabine( in a dosage of 1000 ml / m2).The course of treatment is designed for three weeks. After a week's break, several more such courses are carried out. Focusing on clinical indications, the attending physician can change the dosage( downwards) and freely vary the amount of therapeutic courses.
• Combination therapy involving the use of cisplatin , provides the first infusion of gemcitabine( at a dosage of 70 mg / m2) on the first day of treatment. After this, gemcitabine( 1250 mg / m2) is administered during the first and the eighth day of a three-week treatment course, which is prescribed to be repeated. Correction of the therapeutic dose can be performed by the attending physician.
• For the treatment of gall bladder tumors intravenous infusions of gemcitabine( 1 g / m2) are used on the first, the eighth and the fifteenth day of treatment( duration of therapy is 28 days).Cisplatin is used every second day. Therapeutic courses are regularly repeated.
• In relation to patients with non-small cell malignancies in the lungs, gemcitabine monotherapy provides one infusion per week( the concentration of the solution is 1 g / m2).The duration of the course is three weeks. After a week-long interruption in therapy, the therapy continues according to the same scheme. When using ancillary drugs, the dosage of gemcitabine in the prepared solution is changed( it should be 1250 mg / m2).Schedule of infusion - the first, eighth and twenty-first day of treatment.
• In complex therapy of ovarian cancer of gemcitabine is used together with carboplatin. The dosage of the therapeutic solution is 1 g / m2, the infusion schedule is the same as in the above case. To determine the level of non -hematological toxicity of gemcitabine, the patient should be examined regularly, first of all paying attention to the work of the kidneys and liver. Depending on the results obtained, a step-by-step reduction in the dosage of the drug is made( both during the current therapy cycle and at the beginning of the next one).

Adverse effects of

Gemcitabine may cause a large number of unwanted effects affecting all internal organs and body systems:

• Gemcitabine may only be administered by a specialist with extensive experience in antitumor therapy.
• The dosage and tactics of treatment with gemcitabine( in the form of monotherapy or in combination with other medicines) should be selected individually.
• Given the high likelihood of severe toxic complications( up to a lethal outcome), each patient should receive detailed information from the attending physician about the risks associated with chemotherapy and existing safety measures.
• The initial stage of chemotherapy is mandatory in a hospital.
• Before each infusion of gemcitabine, it is mandatory to monitor the clinical blood test, which involves counting the number of all its constituent elements. If the result of this control indicates a marked suppression of hematopoiesis, the doctor decides either to suspend chemotherapy or adjust the dosage used.
• The more frequent and longer the infusion of gemcitabine - the higher its toxicity.
• With respect to patients with impaired bone marrow function, gemcitabine should be administered with extreme caution.
• The introduction of gemcitabine at a dosage of 1 g / m2( duration of therapy - six weeks), simultaneously with radiotherapy sessions in relation to patients with non-small cell lung cancer, can lead to the formation of a high level of toxicity, accompanied by the development of pneumonia and severe esophagitis( inflammatory lesions of the esophagus mucosa), representing a real threat to life.
• Chemotherapy with gemcitabine for patients with metastases in the liver, as well as those with a history of liver cirrhosis, hepatitis and alcoholism can significantly exacerbate the state of severe hepatic insufficiency.
• The appointment of gemcitabine to patients with insufficient kidney and liver function should be performed with extreme caution, regularly monitoring laboratory data on their performance.
• The same caution is necessary for patients suffering from cardiovascular diseases due to a high risk of complications from the vessels and the heart muscle.
• The use of gemcitabine for the treatment of patients with lung cancer( as well as those with lung metastasis) can trigger unwanted effects on the part of the respiratory system. The emergence of the first manifestations of pneumonia or lung infiltration is an indication for the immediate cessation of chemotherapy with gemcitabine.
• Treatment with gemcitabine( and in the case of monotherapy, and in complex use with other drugs) can trigger a capillary leakage syndrome. If this condition was identified at an early stage of development, taking adequate measures contributes to its rapid elimination. Otherwise, this syndrome can lead to death. The capillary leakage syndrome due to the increased permeability of blood vessels leads to the fact that the proteins and intravascular fluid contained in them are transferred to the interstitial( intercellular) space. This is manifested by the development of acute renal failure, the emergence of generalized edema, rapid increase in body weight, a decrease in blood pressure, pulmonary edema, hypoalbumism( a decrease in the amount of albumin in the blood serum).
• Treatment with gemcitabine against the background of radiotherapy( or when performing its sessions less than a week before the start of chemotherapy) significantly increases the risk of radiation reactions( reactive changes in healthy tissues due to exposure to ionizing radiation).
• Vaccination of a patient undergoing gemcitabine treatment with live vaccines( especially yellow fever) should be discarded. The minimum interval between the completion of chemotherapy and the start of vaccination should be at least twelve weeks.
• Patients of childbearing age( both sexes) should be provided with proven contraceptive measures during gemcitabine treatment.
• In a study on fertility( the ability of sexually mature individuals to reproduce healthy offspring), it was found that gemcitabine in male laboratory mice developed hypospermatogenesis( weakening the process of formation of mature male sex cells).That is why men undergoing gemcitabine treatment are advised to perform only protected sexual intercourses during treatment and six months after chemotherapy. Given the likelihood of infertility as a result of gemcitabine treatment, very prudent before starting treatment resort to the technique of cryopreservation of sperm.
• All manipulations associated with the dissolution and administration of the drug should be performed only by qualified medical personnel, provided that protective measures are taken, including the use of clothing, masks and rubber gloves.

• The digestive system can respond to it by developing nausea and vomiting, diarrhea( or constipation) and severe anorexia, increasing the number of liver enzymes in the blood serum.
• The effect of the drug on the hematopoiesis system of can lead to the development of anemia, leukopenia and thrombocytopenia.
• The response of the urinary system can manifest itself in the form of hematuria( a pathology accompanied by the appearance of blood in the urine) and proteinuria( the so-called presence of protein in the urine).In rare cases, there may be symptomatology resembling hemolytic-uremic syndrome( acute condition accompanied by simultaneous presence of thrombocytopenia, hemolytic anemia and renal failure).If blood tests( lack of platelets, a sharply reduced level of hemoglobin, increased urea, bilirubin and creatinine) indicate that the patient begins to develop hemolytic anemia, therapy with gemcitabine should be stopped immediately. Even despite the abolition of treatment, violations in the work of the kidneys can become irreversible. In this case, hemodialysis( a technique for purifying blood with the aid of an artificial kidney apparatus) may be required.
• The breathing system often responds to gemcitabine with the development of dyspnea( in rare cases until the appearance of bronchospasm), pulmonary edema and interstitial pneumonia( inflammatory pulmonary disease, accompanied by involvement of connective tissues surrounding the interstitium - the alveoli).The occurrence of such symptoms is an indication for the immediate cessation of therapy with gemcitabine.
• The whole body of as a whole in response to taking gemcitabine can respond by the appearance of influenza-like conditions, manifested by the presence of headaches, chills, severe fever, runny nose, cough, increased sweating, myalgia( pain in muscles), feelings of general malaise, asthenia( nervous-mental weakness).
• The effect of gemcitabine on the cardiovascular system sometimes results in the appearance of peripheral edema and, in very rare cases, the development of myocardial infarction and arterial hypotension( lowering blood pressure).
• Gemcitabine therapy can cause dermatological reactions of , which declare themselves to be partial alopecia( hair loss), the development of eczema and stomatitis( with the formation of ulcers in the oral cavity), the appearance of skin and vesicle rashes, accompanied by severe itching and flaking of the skin.
• In patients prone to the emergence of allergic reactions , gemcitabine may trigger anaphylactic shock.
• Treatment with gemcitabine may affect the state of the peripheral and central nervous system , which can make the patient weak and drowsy;it can also trigger the emergence of paresthesia( this is called a sensitivity disorder, accompanied by a sensation of crawling crawling, tingling and numbness).

Overdose of

There are no specific antidotes of gemcitabine. Intravenous infusion of the drug, carried out at a frequency of twice a month( at a dosage not exceeding 5,700 mg / m2) led to the creation of toxicity, the level of which is considered clinically acceptable.

Overdose( if it was still tolerated) leads to the appearance of:

• myelosuppression( a complication characterized by a decrease in the number of platelets and leukocytes in the blood cells);
• marked skin rashes;
• paresthesia.

If an overdose of gemcitabine has provoked a fever in patients with neutropenia( a condition accompanied by a low level of neutrophilic granulocytes in the blood), it is customary to rely on the help of broad-spectrum antibiotics. The effectiveness of their effects is assessed by the results of diagnostic tests and bacteriological studies.

The development of leukopenia( low level of leukocytes in the blood) is an indication to the dynamic observation of patients in order to identify signs of infectious diseases. If necessary, they are treated with antibiotics.

Special instructions

Drug Interaction

• The use of gemcitabine together with the immunosuppressant ( for example, with mercaptopurine, cyclophosphamide, chlorambucil, cyclosporin, azathioprine) may increase the risk of infection.
• The introduction of live vaccines to patients taking gemcitabine , can reduce the production of antibodies, which is fraught with the development of systemic diseases, fraught with a fatal outcome. This presents the greatest danger for patients with a weakened immune system.

Reviews

Anastasia:

Treatment with gemcitabine ended for me with vein thrombosis. To normalize the condition, I was prescribed preparations "Detralex" and "Trombo ACC".

Valentin:

During the next medical examination I was diagnosed with pancreatic cancer, which had already metastasized. The attending physician appointed chemotherapy with gemcitabine. I have already completed four courses. The condition is satisfactory. During the therapy, unpleasant side effects were observed: intestinal colic and diarrhea attacks were very uncomfortable.

Julia:

I received six courses of combined chemotherapy( gemcitabine was used in combination with avastin and carboplatin).Unfortunately, the treatment did not bring any result.

Anastasia:

After surgery to remove the pancreatic tumor, I underwent chemotherapy for six months using gemcitabine. The treatment was not easy for me: after taking the drug, I was suffering from severe abdominal pain and diarrhea. In addition to the tortures experienced, stomatitis developed regularly.

Alexandra:

Complex chemotherapy with a combination of three drugs: avastin, cisplatin and gemcitabine was the hardest test for my body: my stomach ached, I was constantly sick, I could not look at food and literally did not get off the toilet because of painful diarrhea. The only consolation was that the treatment did not lead to hair loss.

Price in Moscow

In pharmacies in Moscow gemcitabine is presented in a fairly wide range and packaging. Equally impressive is the price dispersion, depending on the manufacturer and reflected in the below list.

The cost of the drug Gemcitabine Medak( in the form of lyophilizate for the preparation of solution):

• 200 mg - 1000 rub.
• 1000 mg - 3500-5600 rub.
• 1500 mg - 5950 rub.

Gemcitabine-Aktavis( lyophilizate) will cost the consumer in:

• 460 rub.for a vial containing 200 mg;
• 1700 rub.for 1000 mg of the drug.

The cost of a single vial of Gemcitabine-Ebwee( in the form of a concentrate for infusions, the concentration of the drug - 10 mg / ml) can vary within fairly wide limits:

• 20 ml - 800-1560 rub.
• 50 ml - 2500-3990 rub.
• 100 ml - 4300-5100 rub.

For gemcitabine( lyophilizate) of domestic production, the buyer will pay:

• 700 rub.for 200 mg;
• 2000 rub.- for 1000 mg.

For a package containing 1 g of gemcitabine in the form of a powder, you can pay from 3600 to 4100 rubles in pharmacies in Moscow.

Analogues

Similar products have trademark products:

• "Oncoril";
• "Vizgem";
• "Hercizar";
• Ftorafur;
• "Capecitabine-Vita";
• "Laracite";
• "Viztar";
• "Mercaptopurine";
• "Citogem";
• "Capecitabine-LF";
• "Citin";
• "Cladribine";
• Methotrexate;
• "Cytarabine";
• "Gemtaz";
• "Hydroxycarbamide";
• "Tutabin";
• "Xeloda."

Which is better, Gemzar or Gemcitabine?

The formulation of this issue should be considered incorrect, since the name of the drug "Gemzar"( produced by the international pharmaceutical concern "Eli Lilly and Company", whose headquarters is in the US and its subsidiary "Lilly France SA", located inFrance) is synonymous with the drug "Gemcitabine", and therefore their therapeutic effect is characterized by a complete identity.

Synonyms

Modern manufacturers produce gemcitabine under trade names:

• "Hematics";
• Strigem;
• "Gemzar";
• "Oncohem";
• of Gemciter;
• Dercin;
• "Gemtsibin";
• "Tolchetsit".

All these names, which are synonymous, are used in relation to the same drug.

Conditions for dispensing from pharmacies

Gemcitabine is dispensed only on prescription, certified by the stamp of the medical institution.

Storage conditions and expiration date

Shelf life - 36 months from the date of manufacture. Keep the unopened vials with lyophilized powder in a dry place, protected from sunlight and excluding children.

The air temperature in the place of storage of gemcitabine should not be above twenty-five degrees.

Freshly prepared solution can be stored at the same temperature for a day. Freezing of the solution is unacceptable because of the possibility of its crystallization.