Composition, form of production and packaging
Lyophilizate for the preparation of a solution for white infusions .
1 f.
gemcitabine hydrochloride 228 mg,
which corresponds to the content of gemcitabine 200 mg
Excipients: mannitol, sodium acetate trihydrate, hydrochloric acid and / or sodium hydroxide (to maintain the pH level).
Vials of colorless glass (1) - packs cardboard.
Lyophilizate for the preparation of a solution for white infusions .
1 f.
gemcitabine hydrochloride 1.14 g,
which corresponds to the content of gemcitabine 1 g
Excipients: mannitol, sodium acetate trihydrate, hydrochloric acid and / or sodium hydroxide (to maintain the pH level).
Vials of colorless glass (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
Antitumor drug. Gemcitabine is an antimetabolite of the group of pyrimidine analogues. The drug 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 with the formation of active diphosphate and triphosphate nucleosides. Diphosphate nucleosides inhibit ribonucleotide reductase, which is the only enzyme catalyzing the formation of deoxynucleoside triphosphates required for DNA synthesis. Trisphosphate 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 lysis (apoptosis).
Gemcitabine is also a strong radiosensitizer even at concentrations lower than cytotoxic.
PHARMACOKINETICS
Distribution
V d depends significantly on the duration of the infusion and sex. Binding to plasma proteins is low - less than 10%.
Metabolism
Metabolized in the cells of the liver, kidneys, blood under the action of the enzyme cytidine deaminase in stages, until the formation of an inactive metabolite of 2'-deoxy-2'2'-difluoruridine.
Excretion
The systemic clearance, which ranges from about 30 l / h / m 2 to 90 l / h / m 2 , depends on age and sex (in women, the clearance is 25% less than in men, and with age, the clearance of gemcitabine decreases). T 1/2 - 42-94 min. It is mainly excreted by the kidneys in the form of an inactive metabolite of 2'-deoxy-2 ', 2'-difluoruridine (89%), and also unchanged (less than 10%); less than 1% - with calves.
Pharmacokinetics in special clinical cases
With a reduced function of the kidneys in the body can accumulate inactive metabolite.
INDICATIONS
- non-small cell lung cancer;
- pancreas cancer;
- bladder cancer;
- mammary cancer;
- locally advanced or metastatic cervical cancer.
Gemcitabine in monotherapy or in combination with other antitumor agents also shows activity in ovarian cancer, locally advanced small cell lung cancer and locally advanced refractory testicular cancer.
DOSING MODE
The drug is administered iv in a drop (within 30 minutes).
Gemcitabine is part of many chemotherapeutic regimens, therefore, when selecting doses and the mode of administration of the drug in each individual case, you should refer to the special literature.
Non-small cell lung cancer
As a monotherapy, the recommended dose is 1000 mg / m 2 once a week for 3 weeks, followed by a weekly break, every 28 days. In combination with cisplatin, gemcitabine is administered at a dose of 1250 mg / m 2 on days 1 and 8 of each 21-day cycle or at a dose of 1000 mg / m 2 at 1, 8 and 15 days of each 28-day cycle.
Pancreas cancer
The recommended dose is 1000 mg / m 2 once a week for 7 weeks, followed by a weekly break. Follow-up cycles should consist of infusions, administered once a week for 3 weeks, followed by a one-week break.
Mammary cancer
With the progression of the disease after the first line of therapy, including or without anthracyclines (in contraindications to the use of anthracyclines), gemcitabine is used as monotherapy at a dose of 1000-1200 mg / m 2 at 1, 8 and 15 days every 28 days. In combination with paclitaxel, the drug is administered at a dose of 1250 mg / m 2 on days 1 and 8 of each 21-day cycle.
Cancer of the bladder
The recommended dose is 1250 mg / m 2 at 1, 8 and 15 days every 28 days for monotherapy or 1000 mg / m 2 for 1, 8 and 15 days in combination with cisplatin, which is administered immediately after administration of gemcitabine at a dose of 70 mg / m 2 in 1 or on the 2 day of each 28-day cycle.
Localized or metastatic cervical cancer
Combined therapy is used for this disease. With sequential chemoradiotherapy (neoadjuvant), gemcitabine is administered at a dose of 1250 mg / m 2 on days 1 and 8 of each 21-day cycle. Cisplatin is administered after administration of gemcitabine at a dose of 70 mg / m 2 per day of the cycle against hyperhydration.
In locally advanced cancer with simultaneous chemoradiotherapy, gemcitabine is administered once a week 1-2 hours before the initiation of radiation therapy at a dose of 125 mg / m 2 in combination with cisplatin at a dose of 40 mg / m 2 , which is administered immediately after the administration of gemcitabine .
In case of development of hematological toxicity, the dose of Gemcitabine Pliva may be reduced, or its administration postponed in accordance with the following recommendations: with an absolute number of neutrophils (ACH) more than 1000 / ОјL and platelets more than 100,000 / ОјL, the full recommended dose is used; with ACCH 500-1000 / ОјL or platelets 50 000-100 000 / mkl dose reduced to 75% of the recommended; if the ACCH is less than 500 / ОјL or platelets less than 50,000 / ОјL, the introduction is delayed. To detect non-hematologic toxicity, a regular examination of the patient and control of 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 cycle stepwise. The decision to delay the next administration of the drug should be based on the clinical assessment of the doctor's toxicity dynamics.
Gemcitabine should be used with caution in patients with hepatic impairment or with impaired renal function. Studies in patients with severe impairment of liver and kidney function were not performed.
With renal insufficiency of mild and moderate severity (QC from 30 ml / min to 80 ml / min) there was no marked effect on the pharmacokinetics of gemcitabine.
Changes in the dosing regimen in patients older than 65 years are not required.
The use of gemcitabine in children has not been studied.
Rules for the preparation of an infusion solution
To prepare a solution of Gemcitabine Pliva, use only 0.9% sodium chloride solution without preservatives.
To dissolve Gemcitabine Pliva in a 200 mg bottle add at least 5 ml of solvent, in a bottle of 1 g - 25 ml of solvent, after which the bottle is shaken until the lyophilizate is completely dissolved. The maximum concentration of gemcitabine should not exceed 40 mg / ml. In solutions with a concentration of gemcitabine more than 40 mg / ml, incomplete dissolution is possible.
A prepared solution containing the desired dose of the preparation is diluted with a sufficient amount of 0.9% sodium chloride solution before administration for an IV infusion for 30 minutes. Before the introduction, it should be ensured that there are no suspended particles in the solution.
The prepared solution can be stored at room temperature (15 В° to 30 В° C) for 24 hours; The solution should not be stored in the refrigerator. crystallization may occur.
SIDE EFFECT
Adverse reactions occurring more often than in single cases are listed according to the following gradation: very often (> 10%), often (> 1%, <10%), sometimes (> 0.1%, <1%), rarely > 0.01%, <0.1%), very rarely (<0.01%).
From the hematopoiesis: often - leukopenia, neutropenia, thrombocytopenia, anemia; very rarely - thrombocytosis.
On the part of the digestive system: very often - nausea, vomiting, increased levels of hepatic transaminases, alkaline phosphatase; often - anorexia, diarrhea, constipation, stomatitis, increased bilirubin level.
From the urinary system: very often - proteinuria and hematuria; rarely - hemolytic-uremic syndrome and / or renal failure.
Dermatological reactions: often - skin rash, skin itch, alopecia.
From the respiratory system: very often - shortness of breath; often - cough, rhinitis; sometimes - bronchospasm, interstitial pneumonia, pulmonary edema; rarely - acute respiratory distress syndrome (if these symptoms occur, treatment should be discontinued).
From the cardiovascular system: rarely - lowering blood pressure, myocardial infarction, heart failure, arrhythmia.
From the nervous system: often - headache, drowsiness, insomnia, paresthesia.
Allergic reactions: very rarely - anaphylactic reactions.
Other: very often - influenza-like syndrome, peripheral edema; often - fever, chills, asthenia, back pain, myalgia; sometimes puffiness of the face.
CONTRAINDICATIONS
- Pregnancy;
- lactation period;
- Hypersensitivity to gemcitabine or other components of the drug.
With caution should appoint a drug in violation of the liver and / or kidney function, oppression of bone marrow hematopoiesis (including against the background of concomitant radiation or chemotherapy), with simultaneous radiotherapy, acute infectious diseases of the viral, fungal or bacterial nature (v. ch. chicken pox, shingles).
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy and lactation.
Women and men during the treatment with Gemcitabine Pliva and at least 6 months after the end of treatment should use reliable methods of contraception.
APPLICATION FOR FUNCTIONS OF THE LIVER
Gemcitabine should be used with caution in patients with impaired renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Gemcitabine should be used with caution in patients with hepatic insufficiency.
APPLICATION FOR CHILDREN
The use of gemcitabine in children has not been studied.
APPLICATION IN ELDERLY PATIENTS
Changes in the dosing regimen in patients older than 65 years are not required.
SPECIAL INSTRUCTIONS
Treatment with Gemcitabine Pliva can be performed only under the supervision of a doctor who has experience in the use of antitumor chemotherapy.
Before each administration of the drug, it is necessary to control the number of platelets, leukocytes and neutrophils in the blood. At signs of oppression of bone marrow function, it is necessary to suspend treatment or adjust the dose.
Periodically, it is necessary to assess the function of the kidneys and liver.
Increasing the duration of infusion and the frequency of infusion leads to an increase in toxicity.
The introduction of Gemcitabine Pliva in liver metastases, with hepatitis and alcoholism in history, and with cirrhosis increases the risk of developing liver failure.
When the first signs of hemolytic-uremic syndrome occur, treatment with Gemcitabine Pliva should be stopped.
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 Pliva should be discontinued.
Gemcitabine Pliva can be started to be administered after the resolution of acute radiation reactions or not earlier than 7 days after the end of radiotherapy.
Impact on the ability to drive vehicles and manage mechanisms
During the treatment period, care should be taken when driving vehicles and engaging in potentially hazardous activities requiring increased attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: myelosuppression, paresthesia, severe skin rash.
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.
DRUG INTERACTION
Gemcitabine Pliva has a radiosensitizing effect, so when using the drug on the background of radiotherapy, it is possible to expect intensification of radiation reactions.
Reduces the production of antibodies and increases side effects when using inactivated or live viral vaccines at the same time (the interval between medicinal products should be from 3 to 12 months).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 2 years.
The prepared solution should be stored at a temperature of no higher than 25 В° C for 6 hours.
