Gemcitabine-Ebwee - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Antitumor agent, antimetabolite of the group of pyrimidine analogs, suppresses the synthesis of DNA. It exhibits cyclospecificity by acting on cells in the S and G1 / S phases. Metabolized in the cell by the action of nucleoside kinases to active diphosphate and triphosphate nucleosides. Diphosphate nucleosides inhibit the action of ribonucleotide reductase (the only enzyme catalyzing the formation of deoxynucleoside triphosphates required for DNA synthesis). Triphosphate nucleosides can be inserted into the DNA chain (to a lesser extent, RNA), which leads to the cessation of further DNA synthesis and programmed cell death (apoptosis).In pancreatic cancer, it is considered the preparation of the first line: monotherapy causes clinical improvement in 25-40% of patients, and in 10-15% of patients - partial remission of 11-12 weeks; 23% of patients live more than a year. When gemcitabine is combined with cisplatin, the effectiveness of treatment is increased to 69%. Gemcitabine is also a strong radiosensitizing agent even at concentrations lower than cytotoxic.

Pharmacokinetics:

With intravenous gemcitabine from 0.5 g / m² up to 2.5 g / m² for 0.4-1.2 hours the maximum plasma concentration (C_max) of the drug is achieved 5 minutes after the end of the infusion and is from 3.2 μg / ml to 45.5 μg / ml.

The volume of distribution depends significantly on the duration of infusion and sex: an average of 12.4 l / m²in women and 17.5 l / m² for men. Binding to plasma proteins is low and is less than 10%.

In organism gemcitabine rapidly metabolized by cytidine deaminase in the liver, kidneys, blood and other tissues, resulting in the formation of gemcitabine mono-, di-, and triphosphates, of which gemcitabine di- and triphosphates are considered active.Intracellular metabolites of gemcitabine are not detected in blood plasma or urine. The main metabolite of gemcitabine is 2'-deoxy-2 ', 2'-difluoruridine, is not active and its concentrations are determined in blood plasma and urine. The half-life period varies from 42 to 94 min, depending on the age and sex of the patient. If the recommended dosage regimen is followed, the complete excretion of gemcitabine occurs within 5-11 hours from the start of the infusion. When administered once a week gemcitabine does not accumulate in the body.

Systemic clearance of gemcitabine varies from 29.2 l / h / m² up to 92.2 l / h / m², depending on the sex and age of the patient. The clearance of the drug in women is approximately 25% lower than that of men. Gemcitabine clearance decreases with age. When gemcitabine is administered at the recommended dose of 1000 mg / m² for 30 minutes the lowest value of the clearance in women and men does not require a reduction in the dose of the drug.

Less than 10% of the administered dose of gemcitabine is excreted by the kidneys unchanged. Kidney clearance varies from 2 l / h / m² up to 7 l / h / m². Within a week after the administration of gemcitabine, from 92% to 98% of the dose is excreted from the body: 99% by the kidneys, mainly in the form of 2'-deoxy-2 ', 2'-difluoridin, the rest is excreted by the intestine.

Kinetics of gemcitabine triphosphate

This metabolite is found in mononuclear cells of peripheral blood. The intracellular concentration of gemcitabine triphosphate increases proportionally with an increase in the dose of gemcitabine from 35 mg / m²up to 350 mg / m² with intravenous administration for 30 minutes, which allows the plasma concentration of the drug to reach 0.45 μg / ml. With a plasma concentration of gemcitabine> 5 μg / ml, the concentration of gemcitabine triphosphate does not increase. The half-life (T_1/2) is 1.7-19.4 hours.

With the combination therapy of gemcitabine and paclitaxel, no changes in the pharmacokinetics of the drugs have been observed.

With the combined therapy of gemcitabine and carboplatin, no changes in the pharmacokinetics of the drugs have been observed.

Renal failure of mild or moderate severity (glomerular filtration rate 30-80 ml / min) does not significantly affect the pharmacokinetics of gemcitabine.

Indications:

- locally advanced or metastatic non-small cell lung cancer as first-line therapy in combination with cisplatin or

carboplatin, as well as in monotherapy in elderly patients with functional status equal to 2;

- Unresectable, local-recurring or metastatic breast cancer as part of combination therapy with paclitaxel after neoadjuvant and / or adjuvant therapy with anthracyclines included in the absence of contraindications to their prescription;

- Locally distributed or metastatic urothelial cancer (cancer of the bladder, renal pelvis, ureter, urethra);

- Locally distributed or metastatic epithelial ovarian cancer as monotherapy or in combination with carboplatin in patients with progression of the disease after the first line of therapy based on platinum derivatives;

- Locally spread or metastatic pancreatic cancer;

- Locally spread or metastatic cervical cancer;

- Cancer of the biliary tract.

Shown the efficacy of gemcitabine in disseminated small cell lung cancer and advanced refractory testicular cancer.

Contraindications:

-hypersensitivity to gemcitabine or to any other component of the drug;

- Pregnancy and the period of breastfeeding;

-baby age to 18 years (efficacy and safety of the drug is not established).

Carefully:With caution should be used in patients with impaired liver function (with metastatic liver damage, hepatitis, alcoholism) and / or kidney, in patients with oppression of bone marrow hematopoiesis (including on the background of concomitant radiation or chemotherapy), acute infectious diseases of the viral , fungal or bacterial nature (including chickenpox, shingles), cardiovascular diseases (including in anamnesis), with concomitant radiotherapy.

Pregnancy and lactation:

Adequate and controlled studies on the use of gemcitabine in pregnant and lactating women were not conducted. However, in studies on animals, the drug has teratogenic, embryo and fetotoxic effects, so gemcitabine is contraindicated in pregnancy.

It is not known whether the gemcitabine in breast milk, so when using during lactation it is necessary to refuse breastfeeding of the baby.

Dosing and Administration:

Gemcitabine is administered intravenously drip for 30 minutes.

Before each administration of gemcitabine, it is necessary to control the number of platelets, leukocytes and granulocytes in the blood. At signs of oppression of bone marrow function caused by the drug, it is necessary to suspend treatment or adjust the dose.

Non-small cell lung cancer (locally advanced or metastatic), first-line therapy

Monotherapy: the recommended dose of the drug is 1000 mg / m² on days 1, 8 and 15 of each 28-day cycle.

Combination therapy with cisplatin: the recommended dose of the drug is 1250 mg / m² on days 1 and 8 of each 21-day cycle or 1000 mg / m² on days 1, 8 and 15 of each 28-day cycle. Cisplatinum is administered at a dose of 70 mg / m² in the 1st day of the cycle after the infusion of gemcitabine against a background of hyperhydration.

Combination therapy with carboplatin: the recommended dose of the drug is 1000 mg / m² or 1200 mg / m² on days 1 and 8 of each 21-day cycle.
Carboplatin is introduced from the calculation of AUC (area under the concentration-time curve) 5.0 mg / ml / min on the first day of the cycle after the infusion of gemcitabine.

Breast cancer (unresectable, local-recurring or metastatic)

Combination therapy with paclitaxel: as first-line therapy for the progression of the disease after neoadjuvant and / or adjuvant therapy, including anthracyclines,in the absence of contraindications to them.

Paclitaxel is found in a dose of 175 mg / m² intravenously drip for 3 hours on day 1 of the 21-day cycle, followed by gemcitabine. The recommended dose of the drug is 1250 mg / m² on days 1 and 8 of each 21-day cycle.

Before the start of combination therapy (gemcitabine paclitaxel) the absolute number of granulocytes in the blood of the patient should be at least 1500 / μl.

Urothelial cancer (bladder cancer is locally advanced, metastatic and superficial), renal pelvis, ureter, urethra).

Monotherapy: the recommended dose of the drug is 1250 mg / m² on days 1, 8 and 15 of each 2 8-day cycle.

Combined therapy with iisplatinom: the recommended dose of the drug is 1000 mg / m² on days 1, 8 and 15 in combination with cisplatin, which is administered at a dose of 70 mg / m² immediately after the infusion of gemcitabine on or on day 2 of each 28-day cycle. Clinical studies have shown that with a dose of cisplatin 100 mg / m² more pronounced myelosuppression. Epithelial ovarian cancer (locally advanced or metastatic, resistant to platinum derivatives)

Monotherapy: the recommended dose of the drug is 800-1250 mg / m² on days 1, 8 and 15 of each 28-day cycle.

Combination therapy with carboplatin: the recommended dose of the drug is 1000 mg / m² at 1 and 8 days in combination with carboplatin at the rate of AUC 4.0 mg / ml / min, which is injected immediately after the infusion of gemcitabine on day 1 of each 21-day cycle.

Pancreatic cancer (locally advanced or metastatic, including resistant to fluorouracil therapy)

Ionotherapy: the recommended dose of the drug is 1000 mg / m² Once a week for 7 weeks followed by a weekly break. The preparation is then administered on days 1, 8 and 15 of each 28-day cycle.

Cervical cancer (locally advanced or metastatic) Combined therapy with Iisplatinum: with locally advanced cancer with sequential chemoradiotherapy (neoadjuvant) and with metastatic cancer cisplatin is administered at a dose of 70 mg / m² in the 1st day of the cycle against a background of hyperhydration followed by the introduction of gemcitabine.

Gemcitabine is administered at a dose of 1250 mg / m² on days 1 and 8 of each 21-day cycle.

With locally advanced cancer with simultaneous chemoradiotherapy cisplatin is administered at a dose of 40 mg / m² with the subsequent (immediately after the introduction of cisplatin) by the administration of gemcitabine. Gemcitabine is administered once a week 1-2 hours before the start of radiotherapy at a dose of 1250 mg / m².

Bile duct cancer

Combined therapy with iisplatinom: cisplatin is administered at a dose of 70 mg / m² in the 1st day of the cycle against a background of hyperhydration followed by the introduction of gemcitabine. Gemcitabine is administered at a dose of 1250 mg / m² on days 1 and 8 of each 21-day cycle.

Correction of dose

In case of development of hematological toxicity, the dose of gemcitabine can be reduced, or its administration postponed in accordance with the following schemes:

A. Correction of the dose of gemcitabine within the cycle for urothelial cancer, non-small cell lung cancer, pancreatic cancer as monotherapy or in combination with cisplatin.

The absolute amount of granulocytes (in 1 μl)		The number of platelets (in 1 μl)	% of previous dose
>1000	and	>100000	100
500-1000	or	50000-100000	75
<500	or	<50000	Postpone the introduction

B. Correction of the dose of gemcitabine within the cycle for breast cancer in combination with paclitaxel

The absolute amount of granulocytes (in 1 μl)		The number of platelets (in 1 μl)	% of previous dose
>1200	and	>75000	100
1000-<1200	or	50000-75000	75
700 -<1000	and	>50000	50
<700	or	<50000	Postpone the introduction

B. Correction of the dose of gemcitabine within the cycle for ovarian cancer in combination with carboplatin

The absolute amount of granulocytes (in 1 μl)		The number of platelets (in 1 μl)	% of previous dose
>1500	AND	>100000	100
1000-1500	Or	75000-100000	50
<1000	or	<75000	Postpone the introduction

To detect nonhematological toxicity, a regular examination of the patient and control of the liver and kidney function should be carried out. Depending on the degree of toxicity, the dose can be reduced during each cycle or with the onset of a new step.

The drug should be delayed until, according to the doctor, toxicity is not resolved.

Special patient groups

Patients with impaired renal liver function

Use gemcitabine in patients with hepatic insufficiency or with impaired renal function, caution should be exercised, since there is insufficient data on the use of the drug in this category of patients.

Renal failure of mild or moderate severity (glomerular filtration rate from 30 ml / min to 80 ml / min) has no significant effect on the pharmacokinetics of gemcitabine.

Children

Gemcitabine was studied in limited studies of I and II phases in children with different types of neoplasms. The data of these studies are not enough to prove the effectiveness and safety of gemcitabine in children.

Elderly patients (over 65 years of age)

There is no evidence to suggest that elderly patients need to adjust the dose.

Rules for the preparation of a solution for infusions

In the quality of the solvent used 0.9% solution of sodium chloride (no preservatives) or 5% solution of dextrose.

1.To prepare the solution, you must adhere to the requirements for the preparation of solutions for intravenous administration.

2.Transfer the necessary volume of concentrate in aseptic conditions to a suitable infusion bag or vial.

3.To stir thoroughly.

4.The resulting solution should be clear, from colorless to pale yellow.

5.Before parenteral administration, it is necessary to visually monitor the prepared solution for mechanical impurities and discoloration. Do not inject the solution if particles are found in it.

6.Any unused product or waste must be are disposed of in accordance with local requirements.

7. After dissolving in 0.9% solution of sodium chloride for injections (without preservatives) or 5% solution of dextrose retains physico-chemical stability for 28 days at a temperature of 20 to 25 ° C or in a dark place at a temperature of 2 to 8 ° C (see section "Shelf Life").

From the microbiological point of view, it is recommended to use the drug immediately after opening or dilution. Otherwise, the time and storage conditions are controlled by the person in charge, but when opened and diluted in uncontrolled and unallocated aseptic conditions, the vial after opening and the diluted infusion solution should be stored at room temperature for no more than 24 hours.

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (≥1/10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥1 / 10000 to <1/1000), very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

On the part of the blood and lymphatic system

Very often: leukopenia (grade 3 neutropenia = 19.3%, 4 degrees = 6%). Myelosuppression usually has an easy or moderate degree and is manifested mainly by a change in the number of granulocytes), thrombocytopenia, anemia;

often: febrile neutropenia;

Very rarely: thrombocytosis.

From the immune system

very rarely: anaphylactoid reaction.

From the nervous system

often: headache, insomnia, drowsiness.

very rarely: a syndrome of reversible posterior encephalopathy (SOPE).

From the side of the cardiovascular system

infrequently: heart failure (including progression of existing heart failure), cerebral circulation disorder, arrhythmia, predominantly supraventricular;

rarely: myocardial infarction, peripheral vasculitis (sometimes the development of gangrene is possible), lowering blood pressure;

very rarely: a syndrome of increased capillary permeability.

From the respiratory system

very often: dyspnea - usually mild, rapidly disappearing without treatment;

often: cough, rhinitis;

infrequently: interstitial pneumonitis, bronchospasm - usually of mild degree and carries

Transient, but may require parenteral treatment;

rarely: acute respiratory distress syndrome, pulmonary edema.

From the side of the digestive system

very often: nausea, vomiting, increased activity of "liver" transaminases and alkaline phosphatase;

often: diarrhea, stomatitis and ulcers of the oral mucosa, constipation,increased bilirubin concentration;

infrequent: severe hepatotoxicity, including hepatic insufficiency and death;

rarely: increased activity of gamma-glutamyltransferase;

very rarely: ischemic colitis.

From the skin and its derivatives

very often: skin allergic rash, often accompanied by itching, alopecia;

often: itching, increased sweating;

rarely: reactions from the skin of severe degree, including desquamation and bullous eruptions, ulceration, the formation of blisters and ulcers, skin peeling;

very rarely: toxic epidermal necrolysis, Stevens-Johnson syndrome.

From the genitourinary system

very often: hematuria, mild proteinuria;

infrequently: renal failure, hemolytic uremic syndrome.

From the musculoskeletal system

often: back pain, myalgia.

Other

very common: grinio-like syndrome (the most frequent symptoms are fever, headache, asthenia, chills, myalgia, anorexia, and cough, rhinitis, malaise, sweating), peripheral swelling, including swelling of the face, usually reversible after cessation treatment;

often: fever, asthenia, chills, anorexia;

rarely: reactions at the injection site, toxicity of radiation therapy, reactivation of radiation burns.

The use of gemcitabine in combination c paclitaxel in breast cancer

Undesirable effects of III and IV severity
	Number (%) of patients The total number is 262
	III degree	IV degree
Hematologiststoxic toxicity
Anemia	15(5,7)	3(1,1)
Thrombocytopenia	14(5,3)	1 (0,4)
Neutropenia	82(31,3)	45 (17,2)*
Non-hematological toxicity
Febrile neutropenia	12(4,6)	1 (0.4)
Fatigability	15(5,7)	2(0,8)
Diarrhea	8(3.1)	0
Motor Neuropathy	6 (2,3)	1 (0,4)
Sensory Neuropathy	14(5,3)	1 (0.4)

* Neutropenia of grade 4 lasting more than 7 days was observed in 12.6% of patients in the combination treatment group and in 5.0% of patients in the paclitaxel treatment group.

The use of gemcitabine in combination with cisplatin in bladder cancer

Undesirable effects of III and IV severity
	Number (%) of patients The total number is 200
	III degree	IV degree
Hematologiststoxic toxicity
Anemia	47 (24)	7 (4)
Thrombocytopenia	57 (29)	57 (29)
Non-hematological toxicity
Nausea and vomiting	44(22)	0 (0)
Diarrhea	6(3)	0 (0)
Infections	4 (2)	1 (1)
Stomatitis	2(1)	0 (0)

The use of gemcitabine in combination with carboplatin in ovarian cancer

Undesirable effects of III and IV severity
	Number (%) of patients The total number is 175
	III degree	IV degree
Hematologiststoxic toxicity
Anemia	39 (22,3)	9 (5,1)
Thrombocytopenia	53 (30,3)	8 (4,6)
Neutropenia	73 (41,7)	50 (28,6)
Leukopenia	84 (48,0)	9 (5,1)
Non-hematological toxicity
Bleeding	3 (1,8)	0 (0)
Febrile neutropenia	2 (1,1)	0 (0)
Infection without neutropenia	0 (0)	1 (0,6)

In the combination therapy group, the frequency of sensory neuropathy was also higher than in the carboplate monotherapy group.

Overdose:Symptoms: myelosuppression, paresthesia, severe skin rash. With intravenous infusions of the drug in doses up to 5700 mg / m², performed for 30 minutes every 2 weeks, the level of toxicity was clinically acceptable.

Treatment: there is no specific antidote. If you suspect an overdose, the patient should be under constant medical supervision, including the calculation of the blood formula; if necessary, symptomatic treatment.

Interaction:

Studies on the interaction of gemcitabine with other drugs have not been conducted.

Pre-clinical and clinical studies have shown that gemcitabine has a radiosensitizing effect. In a single study, in which gemcitabine in a dose of 1000 mg / m² for 6 consecutive weeks was applied simultaneously with the therapeutic irradiation of the chest in patients with non-small cell lung cancer, significant toxicity was noted in the form of severe and potentially life-threatening inflammation of the mucositis (mucositis), mainly esophagitis and pneumonitis, especially in patients receiving large volumes of radiotherapy [median volumes of treatment - 4795 cm³]. Subsequent studies (phase II studies with non-small cell lung cancer) suggest that gemcitabine can be used at lower doses together with radiotherapy with predictable toxicity. Radiation therapy on the chest region of 66 Gy was carried out simultaneously with gemcitabine therapy (dose 600 mg / m², 4 injections) and cisplatin (dose of 80 mg / m administration) for 6 weeks. The optimal mode of safe use of gemcitabine together with therapeutic doses for all types of tumors has not yet been determined. The introduction of gemcitabine more than 7 days before the start of radiotherapy or more than 7 days after its completion is not accompanied by an increase in toxicity.Reduces the production of antibodies and enhances side effects while using inactivated or live viral vaccines (the interval between vaccine use should be from 3 to 12 months). The frequency of hematological toxicity of grade 3 and 4, especially neutropenia, increases with the combined use of gemcitabine and paclitaxel. However, an increase in the incidence of these side effects is not associated with an increase in the incidence of infections or bleeding episodes. Increased fatigue and febrile neutropenia are more common with gemcitabine in combination with paclitaxel. Increased fatigue, not associated with anemia, usually disappears after the first cycle of therapy.

Special instructions:

Treatment with Gemcitabine-Ebewe® can be done only under the supervision of a doctor who has experience in the use of antitumor chemotherapy. Gemcitabine-Ebove® can be used both as a monotherapy and in combination with other antitumor drugs. The dose and scheme of the drug is selected individually. Taking into account the risk of developing severe toxic reactions, including fatalities,the doctor must inform the patient in detail about the possible risk and the necessary safety measures. Start treatment is necessary in a hospital.

Before each administration of the drug Gemcitabine-Ebove® it is necessary to monitor the clinical analysis of blood with quantitative counting of blood elements (platelets, leukocytes, neutrophils). When oppression of bone marrow function, it is necessary to suspend treatment or adjust the dose of Gemcitabine-Ebove®.

An increase in the duration and frequency of infusion leads to an increase in the toxicity of Gemcitabine-Ebove®. The drug should be administered with caution to patients with impaired bone marrow function. Gemcitabine, as well as for other cytotoxic drugs, is characterized by the risk of cumulative myelosuppression against a background of combined chemoherapy. The use of Gemcitabine-Ebove® in patients with liver metastases or with hepatitis, alcoholism or cirrhosis in the history of the liver can contribute to worsening of concomitant hepatic insufficiency. Gemcitabine-Ebevé® should be used with caution in patients with hepatic insufficiency or with impaired renal function, since to date,obtained in the course of clinical trials, is not sufficient for clear recommendations on changing the dose of the drug in these categories of patients.

Periodically, it is necessary to perform an assessment of laboratory parameters of kidney and liver function.

In patients receiving gemcitabine, rarely reveal the clinical symptoms of hemolyticuremic syndrome (HUS). The HUS is a state that poses a potential threat to life. Gemcitabine should be discontinued with the appearance of the first symptoms indicative of microangiopathic hemolytic anemia, such as a rapid decrease in hemoglobin with concomitant thrombocytopenia, an increase in the serum of bilirubin, creatinine, residual urea nitrogen, or lactate dehydrogenase.

Even with the withdrawal of therapy, kidney failure may be irreversible and hemodialysis will be necessary.

In patients with lung cancer or lung metastases, the risk of side effects from the respiratory system is increased. When the first signs of pneumonitis or the appearance of infiltrates in the lungs, treatment with Gemcitabine-Ebevé® should be discontinued.

In patients who received gemcitabine as a monotherapy or in combination with other chemotherapeutic drugs, the syndrome of increased permeability of capillaries was recorded. If detected at early stages and adequate measures, the condition is usually treatable, but deaths have also been reported. This condition is characterized by increased vascular permeability and the transfer of intravascular fluid and proteins to the interstitial space. Clinical signs include generalized edema, weight gain, hypoalbuminemia, marked reduction in blood pressure, acute renal failure, and pulmonary edema. If during the therapy with gemcitabine develops a syndrome of increased permeability of capillaries, it is necessary to stop the use of gemcitabine and maintain maintenance therapy. The syndrome of increased permeability of capillaries can develop in later cycles, the literature describes its association with respiratory distress syndrome. In the course of gemcitabine therapy, pulmonary disorders associated with the administration of the drug are detected, in some cases severe (such as pulmonary edema, interstitial pivonitis or acute respiratory distress syndrome).With the development of these effects, the question of reversing gemcitabine therapy should be addressed. With early supportive activities, it is possible to improve the condition.

The optimal regimen for the safe administration of gemcitabine in combination with therapeutic regimens of radiotherapy has not been determined to date.

Concomitant radiation therapy (simultaneously with the introduction of gemcitabine or less than 7 days before the start of treatment) increases the risk of radiation reactions.

Because of the risk of developing cardiac and / or vascular disorders with gemcitabine, extreme care should be taken when treating patients with cardiovascular disease with gemcitabine.

A syndrome of reversible posterior encephalopathy (SOPE) with potentially serious consequences was reported in patients taking gemcitabine in a mode of mopoterapii or together with other and chemotherapeutic agents. In most patients with SZOE, gemcitabine was reported to have acute blood pressure elevation and convulsions, but this syndrome can also manifest itself as headache, lethargy, confusion and blindness. The diagnosis is reliably confirmed by magnetic resonance imaging (MRI).The SZOE is usually reversible if appropriate therapeutic measures are taken. If SZOE develops during therapy, gemcitabine should be completely discontinued and maintenance therapy should be carried out, including blood pressure monitoring, and anticonvulsant therapy. The use of the vaccine against yellow fever and other live attenuated vaccines during treatment with gemcitabine is not recommended. The interval between the use of vaccines and the end of treatment with gemcitabine should be from 3 to 12 months.

Men and women of childbearing age should be treated with Gemcitabine-Ebove® and at least 6 months after the treatment, reliable methods of contraception should be used.

In research on fertility gemcitabine induced gynsonermatoglosis in male mice. Therefore, men receiving gemcitabine, it is recommended to avoid unprotected sex during the use of the drug and up to 6 months after therapy, and as before starting treatment, use the method of cryopreservation of sperm due to the probability of infertility due to gemcitabine treatment. Gemcitabine-Ebweve® 10 mg contains 1.07 mg (0.047 mmol), 200 mg contains 21.49 mg (0.93 mmol), 500 mg contains 53.74 mg (2.34 mmol), and 1000 mg contains 107.47 mg (4.67 mmol) of sodium in one vial.

This should be taken into account when appointing the drug to patients who follow a diet with a controlled sodium content.

Precautions should be observed when working with Gemcitabine-Ebweve®:

In case of contact with Gemcitabine-Ebove® with skin or mucous membranes - thoroughly rinse with water (mucous membranes) or water with soap (skin). Dissolution, dilution and administration of the drug are carried out by trained medical personnel with observance of protective measures (gloves, masks, clothing, etc.).

Effect on the ability to drive transp. cf. and fur:

Because of the likelihood of side effects, such as drowsiness, headache, caution should be exercised when engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

When these undesirable phenomena appear, one should refrain from performing these activities.

Form release / dosage:Concentrate for the preparation of a solution for infusions of 10 mg / ml.

Packaging:

To 20 ml, 50 ml and 100 ml in bottles of colorless glass, type 1 (Hept. F.), sealed with rubber (brombutyl rubber) stopper with fluoropolymer coating, under aluminum rolling.

For 1, 5 or 10 bottles, along with the instructions for use, put in a cardboard box.

Storage conditions:

In the dark place at a temperature of 15 to 25 ° C.

Do not freeze or store in a refrigerator.

Keep out of the reach of children.

Special precautions for the destruction of unused medications

Remains of the preparation, all instruments and materials used to prepare Gemcitabine-Ebove® infusion solutions must be disposed of in accordance with the standard hospital procedure for the disposal of cytotoxic substances, taking into account existing regulations for the destruction of hazardous waste.

Shelf life:

3 years.

After opening, the drug should be stored at a temperature of 20 to 25 ° C for not more than 28 days, at a temperature of 2 to 8 ° C it should not be stored for more than 24 hours.

Ready-to-use solution for infusions in a 5% dextrose solution or in 0.9% sodium chloride solution should be stored for no longer than 28 days at a temperature of 20-25 ° C or in a dark place at a temperature of 2 to 8 ° C. Do not use the drug after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002241

Date of registration:23.09.2013 / 21.08.2014

Expiration Date:23.09.2018

The owner of the registration certificate:Ebewe Pharma Gesmb.b. Nfg. KGEbewe Pharma Gesmb.b. Nfg. KG Austria

Manufacturer: & nbsp

EBEWE PHARMA, Ges.m.b.H.Nfg.KG Austria

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp22.03.2017

Illustrated instructions

Instructions

Gemcitabine-Ebwee (Gemcitabine-Ebewe)