Цитогем®

General characteristics. Structure:

Lyophilisate for preparation of solution for infusions of white or almost white color, in the form of flat cake or separate units, or in the form of free powder, free from visible foreign particles.
1 фл.
gemcitabine (in the form of a hydrochloride) 200 mg
Excipients: Mannitolum, sodium acetate, sodium hydroxide.
Bottles of colourless glass (1) – a pack cardboard.
Lyophilisate for preparation of solution for infusions of white or almost white color, in a look
flat cake or separate units, or in the form of free powder; free from visible foreign particles.
1 фл.
gemcitabine (in the form of a hydrochloride) 1000 mg
Excipients: Mannitolum, sodium acetate, sodium hydroxide.
Bottles of colourless glass (1) – a pack cardboard.

Pharmacological properties:

Antineoplastic drug. Antimetabolite of group of analogs of a pyrimidine.
Drug suppresses DNA synthesis. Shows cyclospecificity, affecting cells in the phases S and G1/S. It is metabolized in a cell under influence нуклеозидкиназ to active diphosphatic and trifosfatny nucleosides.
Diphosphatic nucleosides inhibit the ribonukleotidreduktazu-only enzyme catalyzing formation of the dezoksinukleozidtrifosfat necessary for DNA synthesis.
Trifosfatny nucleosides are capable to be built in DNA chain (to a lesser extent by RNA) that leads to the termination of further synthesis of DNA and the programmed lysis of a cell (apoptosis).
Gemcitabine is also strong radio sensibilizing means even in concentration lower, than cytotoxic.

Indications to use:

Not small-celled cancer of a lung; breast cancer; pancreatic cancer; bladder cancer.
Gemcitabine in monotherapy or in a combination with other antineoplastic means also shows activity at ovarian cancer, locally-spread small-celled cancer of a lung and locally-spread refractory cancer of a small egg.

Route of administration and doses:

Цитогем® it is necessary to enter in/in kapelno within 30 min.
Gemcitabine is a part of many chemotherapeutic modes in this connection at selection of doses and the mode of administration of drug in each individual case it is necessary to address special literature.
Not small-celled cancer of a lung
As monotherapy the recommended dose makes 1000 mg/sq.m within 3 weeks with the subsequent week break, each 28 days once a week. With Cisplatinum gemcitabine is entered into combinations in a dose of 1250 mg/sq.m in 1_y and 8_y days of everyone 21_dnevnogo a cycle or in a dose of 1000 mg/sq.m in 1, 8 i15_ydnikazhdogo 28_dnevnogo a cycle.
Breast cancer
When progressing a disease after the first line of the therapy including anthracyclines or without them (at a contraindication of use of anthracyclines) gemcitabine is applied as monotherapy in a dose of 1000_1200 mg/sq.m in 1, 8 and 15_y days of everyone 28_dnevnogo a cycle. In a combination with paklitaksely drug is used in a dose of 1250 mg/sq.m in 1_y and 8_y days of each 21-day cycle.
Pancreatic cancer
The recommended dose – 1000 mg/sq.m once a week within 7 weeks with the subsequent week break. The subsequent cycles have to consist of the infusions spent once a week during 3_kh weeks with the subsequent week break.
Bladder cancer
The recommended dose – 1250 mg/sq.m in 1, 8 and 15_y days each 28 days at monotherapy or 1000 mg/sq.m in 1, 8 and 15 days in combination with Cisplatinum which is entered right after administration of gemcitabine in a dose of 70 mg/sq.m in 1_y or 2_y day of everyone 28_dnevnogo a cycle. In case of development of hematologic toxicity the dose of gemcitabine can be reduced or its introduction is postponed according to the following scheme: at quantity of granulocytes> 1000/mkl and thrombocytes> 100 000/mkl use the full recommended dose. At quantity of granulocytes 500_1000/mkl or thrombocytes 50 000_100 000/mkl the dose is reduced to 75% of recommended. If number of granulocytes <500/mkl or thrombocytes <50 000/mkl, postpone administration of drug. For detection of not hematologic toxicity it is necessary to conduct regular examination of the patient and to control function of a liver and kidneys. Depending on toxicity degree the dose can be reduced during each cycle or from the beginning of a new cycle in steps. The decision on a delay of the next administration of drug has to be based on clinical assessment by the doctor of dynamics of toxicity.
At patients with abnormal liver functions and kidneys gemcitabine should be applied with care as drug use studies at patients of these groups were not conducted.
Renal failure easy or moderate severity (KK of 30-80 ml/min.)
does not exert noticeable impact on gemcitabine pharmacokinetics.
At patients 65 years of dose adjustment of drug are aged more senior it is not required.
Use of gemcitabine for children was not studied.
Rules of preparation of infusion solution
For preparation of solution of Tsitogem it is necessary to use only 0.9% chloride sodium solution without preservatives. For dissolution of 200 mg of gemcitabine add not less than 5 ml of solvent to a bottle and stir up before full dissolution of lyophilisate. The maximum concentration of gemcitabine should not exceed 40 mg/ml. In solutions with concentration of gemcitabine more than 40 mg/ml perhaps incomplete dissolution. The prepared solution containing the necessary dose of drug before introduction is diluted with enough by 0.9% of solution of sodium of chloride for carrying out in/in injections within 30 min. Before introduction it is necessary to be convinced of absence in solution of suspended particles.

Features of use:

Treatment by the drug Tsitogem® should be carried out only under observation of the doctor having experience of use of antineoplastic therapy.
Before each administration of the drug Tsitogem® it is necessary to control quantity of thrombocytes, leukocytes and granulocytes in blood. At signs of oppression of function of marrow it is necessary to suspend treatment or to correct a drug dose. Periodically it is necessary to carry out assessment of function of a liver and kidneys.
Increase in duration of infusion and frequency of introductions leads to increase
toxicity.
Administration of the drug Tsitogem® at metastasises in a liver, hepatitis and alcoholism in the anamnesis, and also at cirrhosis increases risk of development of a liver failure. At emergence of the first clinical signs of a hemolitic uraemic syndrome treatment by the drug Tsitogem® should be stopped. At patients with cancer of a lung or metastasises in lungs the risk of emergence of side effects from respiratory system is increased. At the first symptoms of a pneumonitis or emergence of infiltrates in lungs treatment by gemcitabine should be stopped.
The drug Tsitogem® should begin to be administered after permission of acute beam reactions or not earlier than in 7 days after the end of radiation therapy.
Influence on ability to driving of motor transport and to control of mechanisms
During treatment by gemcitabine it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From system of a hemopoiesis: leukopenia, thrombocytopenia, anemia.
From the alimentary system: nausea, vomiting, lock or diarrhea, stomatitis,
hyperbilirubinemia, increase in activity of hepatic transaminases and ShchF level.
From TsNS and peripheral nervous system: headache, drowsiness, sleep disorders, paresthesias.
From respiratory system: short wind, cough, rhinitis; seldom – a bronchospasm,
intersticial pneumonia, fluid lungs, respiratory distress syndrome
(at emergence treatment should be stopped).
From outside сердечно&сосудистой systems: decrease in the ABP, myocardial infarction, cordial
insufficiency, arrhythmia.
From an urinary system: proteinuria, hamaturia; seldom – a hemolitic uraemic syndrome.
Dermatological reactions: skin rashes, skin itch, alopecia.
Allergic reactions: very seldom – anaphylactic reactions.
Others: often-grippopodobny syndrome, peripheral hypostases, fervescence, fever, adynamy, dorsodynias, mialgiya, puffiness of the person.

Interaction with other medicines:

Gemcitabine possesses the radio sensibilizing action in this connection at use of drug against the background of performing radiation therapy it is possible to expect strengthening of beam reactions.
Reduces development of antibodies and strengthens side effects at simultaneous use of the inactivated or live vaccines (the interval between use of medicines has to be from 3 to 12 months).

Contraindications:

Children's age (data on efficiency and safety are absent);
pregnancy; breastfeeding period; hypersensitivity to drug components.
With care it is necessary to use drug at an abnormal liver function and/or
kidneys, oppression of a marrowy hemopoiesis (including against the background of accompanying beam or chemotherapy), at the same time carried out radiation therapy, acute infectious diseases of the virus, fungal or bacterial nature (including chicken pox, shingles).

PREGNANCY AND LACTATION
Use of drug at pregnancy and during breastfeeding is contraindicated.
Women and men of childbearing age during therapy by the drug Tsitogem® and, at least, within 6 months later should apply reliable ways of contraception.

Overdose:

Symptoms: strengthening of above-mentioned by-effects.
Treatment: at suspicion on overdose the patient has to be under the constant medical observation including careful control of blood indicators. If necessary – a symptomatic treatment. The antidote is unknown.

Storage conditions:

List B. Drug should be stored in the unavailable to children, dry, protected from light place at a temperature nevyshe25 °C; not to freeze. Period of validity-2 of year.
The prepared solution can be stored at the room temperature from 15 ° to 30 °C during 24 h; it is not necessary to freeze in order to avoid crystallization.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of solution for infusions, 200 mg. On 200 mg in the bottles from colourless glass corked by rubber bungs and aluminum-plastic caps with safety plastic lids of violet color. On 1 фл. in a cardboard pack.

Lyophilisate for preparation of solution for infusions, 1000 mg. On 1000 mg in the bottles from colourless glass corked by rubber bungs and aluminum-plastic caps with safety plastic lids of green color. On 1 фл. in a cardboard pack.