Gemzar

Gemzar – an antimetabolite from group of analogs of a pyrimidine, antineoplastic drug.

Form of release and structure

Dosage form – lyophilisate for preparation of solution for infusions (in glass bottles, on 1 bottle in a pack cardboard).

Active ingredient: gemcitabine (in the form of a hydrochloride), in 1 bottle – 200 or 1000 mg.

Additional components: Mannitolum, sodium acetate.

Indications to use

Locally-spread and metastatic cancer of the following bodies:

• Bladder;
• Ureter;
• Renal pelvis;
• Urethra;
• Pancreas;
• Neck of uterus;
• Ovaries (as monodrug or in a combination with karboplatiny at patients with the progressing disease after the termination of the first line of therapy using platinum derivatives);
• Not small-celled cancer of a lung (performing therapy of the first line in combination with karboplatiny or Cisplatinum, and also as monodrug at patients of advanced age with the functional status 2).

Also Gemzar is effective at the following diseases:

• Cancer of biliary tract;
• Widespread small-celled cancer of a lung;
• Widespread refractory cancer of a small egg;
• Metastatic, mestnoretsidiviruyushchy and nerezektabelny breast cancer (in combination with the paklitaksely ambassador of performing adjuvant and/or neoadjuvant therapy using anthracyclines if to them there were no contraindications).

Contraindications

Absolute:

• Pregnancy;
• Lactation;
• Age up to 18 years;
• Hypersensitivity to drug.

Relative (because of risk of development of complications it is necessary to observe extra care):

• Acute infectious diseases of a fungal, bacterial and virus origin;
• Dysfunction of kidneys/liver;
• Oppression of a marrowy hemopoiesis, including owing to the accompanying himio-or radiation therapy.

Route of administration and dosage

The solution prepared from lyophilisate is entered intravenously kapelno within 30 minutes. As solvent use only 0,9% chloride sodium solution (without preservatives): contents of a bottle of 200 mg are dissolved at least in 5 ml, and a bottle of 1000 mg – in 25 ml of solution then accurately shake up a bottle before full dissolution of powder (solution has to be transparent, not have mechanical impurity).

Before introduction the prepared gemcitabine solution with the maintenance of the necessary dose is diluted with solution of sodium of chloride by 0,9% in the quantity sufficient for performing 30-minute intravenous infusion.

The recommended Gemzar's doses depending on indications and schemes of therapy:

Locally-spread or metastatic not small-celled cancer of a lung, first line of therapy:

• Monotherapy: on 1000 ^mg/sq.m in the 1st, 8th and 15th days of each 28-day cycle;
• Combination therapy with Cisplatinum: on 1250 ^mg/sq.m in the 1st and 8th days of each 21-day cycle or on 1000 ^mg/sq.m in the 1st, 8th and 15th days of each 28-day cycle. Cisplatinum enter in the 1st day of a cycle against the background of an overhydratation after Gemzar's infusion in a dose 70 ^mg/sq.m;
• Combination therapy with karboplatiny: on 1000 or 1200 ^mg/sq.m in the 1st and 8th days of each 21-day cycle. Karboplatin enter in the 1st day of a cycle after Gemzar's infusion in a dose at the rate of AUC 5 mg/ml/minute.

Epithelial ovarian cancer, locally-spread, metastatic or resistant to platinum derivatives:

• Monotherapy: on 800-1250 ^mg/sq.m in the 1st, 8th and 15th days of each 28-day cycle;
• Combination therapy with karboplatiny: on 1000 ^mg/sq.m in the 1st and 8th days of each 21-day cycle. Karboplatin enter in the 1st day of each cycle right after Gemzar's infusion in a dose at the rate of AUC 4 mg/ml/minute.

Urothelial cancer (superficial, locally-spread and metastatic cancer of a bladder, cancer of an urethra, ureter, renal pelvis):

• Monotherapy: on 1250 ^mg/sq.m in the 1st, 8th and 15th days of each 28-day cycle;
• Combination therapy with Cisplatinum: Gemzar enter 1000 ^mg/sq.m in the 1st, 8th and 15th days of each 28-day cycle, Cisplatinum – in the 1st or 2nd day of a cycle right after Gemzar's infusion in a dose of 70 ^mg/sq.m.

At a mestnoretsidiviruyushchy, metastatic, nerezektabelny breast cancer carry out a combination therapy with paklitaksely (when progressing a disease after performing neoadjuvant and/or adjuvant therapy using anthracyclines (on condition of lack of contraindications to them) as therapy of the first line): paklitakset enter intravenously kapelno slowly (within 3 hours) in a dose of 175 ^mg/sq.m in the 1st day of a 21-day cycle before gemcitabine, Gemzar enter 1250 ^mg/sq.m in the 1st and 8th days of each 21-day cycle. Before such therapy check absolute number of granulocytes in blood – it has to be not less 1500/mkl.

At locally-spread, metastatic (including resistant to therapy 5-ftoruratsily) a pancreatic cancer carry out monotherapy by drug: within 7 weeks – on 1000 ^mg/sq.m once a week with the subsequent 7-day break, further – in the same dose in the 1st, 8th and 15th days of each 28-day cycle.

At cancer of biliary tract carry out a combination therapy with Cisplatinum. Cisplatinum enter against the background of an overhydratation in the 1st day of a cycle in a dose 70 ^mg/sq.m before administration of gemcitabine. Gemzar enter 1250 ^mg/sq.m in the 1st and 8th days of each 21-day cycle.

At locally-spread or metastatic cancer of a neck of uterus carry out a combination therapy with Cisplatinum. At locally-spread cancer and performing consecutive himioluchevy therapy (neoadjyuvantno), and also at metastatic cancer Cisplatinum enter against the background of an overhydratation in the 1st day of a cycle before gemcitabine in a dose 70 ^mg/sq.m. Gemzar enter 1250 ^mg/sq.m in the 1st and 8th days of each 21-day cycle.

At locally-spread cancer and simultaneous performing himioluchevy therapy Cisplatinum enter 40 ^mg/sq.m in a dose. Gemzar enter 1 time in 7 days in a dose of 125 ^mg/sq.m directly after introduction of Cisplatinum, in 1-2 hours prior to radiation therapy.

Dose adjustment

If during therapy hematologic toxicity develops, it is necessary to postpone administration of drug or to lower a gemcitabine dose according to the following schemes.

Dose adjustment within a cycle (as monotherapy or in a combination with Cisplatinum) at a pancreatic cancer, not small-celled cancer of a lung and urothelial cancer:

• Absolute quantity of granulocytes in 1 мкл> 1000 and number of thrombocytes in 1 мкл> 100 000: the dose does not change;
• Absolute quantity of granulocytes in 1 мкл 500-1000 or number of thrombocytes in 1 мкл 50 000-100 000: 75% of the previous dose;
• Absolute quantity of granulocytes in 1 мкл <500 or number of thrombocytes in 1 мкл <50 000: introduction should be postponed.

Dose adjustment within the carried-out cycle (in combination with paklitaksely) at a breast cancer:

• Absolute quantity of granulocytes in 1 мкл ≥1200 and number of thrombocytes in 1 мкл> 75 000: the dose does not change;
• Absolute quantity of granulocytes in 1 мкл 1000 - <1200 or number of thrombocytes in 1 мкл 50 000-75 000: 75% of the previous dose;
• Absolute quantity of granulocytes in 1 мкл 700 - <1000 and number of thrombocytes in 1 мкл ≥50 000: 50% of the previous dose;
• Absolute quantity of granulocytes in 1 мкл <700 or number of thrombocytes in 1 мкл <50 000: introduction should be postponed.

Dose adjustment within the carried-out cycle (in combination with karboplatiny) at ovarian cancer:

• Absolute quantity of granulocytes in 1 мкл> 1500 and number of thrombocytes in 1 мкл ≥100 000: the dose does not change;
• Absolute quantity of granulocytes in 1 мкл 1000-1500 or number of thrombocytes in 1 мкл 75 000-100 000: 50% of the previous dose;
• Absolute quantity of granulocytes in 1 мкл <1000 or number of thrombocytes in 1 мкл <75 000: introduction should be postponed.

In cases when it is necessary to postpone Gemzar's introduction, duration of a break is determined by the doctor.

In time to reveal not hematologic toxicity, it is regularly necessary to conduct examination of the patient, to control functions of his kidneys and a liver. Depending on the revealed toxicity degree the dose can be reduced in steps from the beginning of a new cycle or during each cycle.

Side effects

• System of a hemopoiesis: very often (≥10%) – thrombocytopenia, a leukopenia and anemia; often (≥1%, <10%) – a febrile neutropenia; very seldom (<0,01%) – a thrombocytosis;
• Respiratory system: very often – an asthma; often – rhinitis and cough; infrequently (≥0,1%, <1%) – a bronchospasm;
• Cardiovascular system: very often – hypostases (including peripheral); infrequently – arrhythmia (supraventricular is more often); seldom (≥0,01%, <0,1%) – a lowering of arterial pressure, a myocardial infarction;
• Nervous system: often – drowsiness, sleep disorders, a headache;
• Alimentary system: very often – nausea and vomiting, functional disturbance of a liver (usually easy degree therefore the termination of treatment is required seldom); often – stomatitis, diarrhea and a lock;
• Urinary system: very often – a hamaturia, easy degree of a proteinuria;
• Musculoskeletal system: often – dorsodynias, a mialgiya;
• Skin and hypodermic fabrics: very often – skin rashes of easy degree with an itch, an alopecia (usually insignificant); often – perspiration, an itch; seldom – vesicles, ulcers;
• Allergic reactions: very seldom – anaphylactic and anaphylactoid reactions;
• Others: very often – a grippopodobny syndrome (a headache, an indisposition, an adynamy, a fever, fervescence); seldom – reactions in a drug injection site.

In the post-marketing period the following side effects were also noted:

• Cardiovascular system: infrequently – heart failure; seldom – a peripheral vasculitis, gangrene; very seldom – a syndrome of a hyperpermeability of capillaries;
• Respiratory system: infrequently – an intersticial pneumonitis; seldom – a fluid lungs, a respiratory distress syndrome;
• Alimentary system: very seldom – ischemic colitis;
• Urinary system: infrequently – a gemolitiko-uraemic syndrome;
• Biliary tract and liver: very often – increase in an alkaline phosphatase, aspartate aminotransferase, alaninaminotranspherase; often – increase in concentration of bilirubin; infrequently – a heavy hepatotoxic, including a liver failure; seldom – increase in activity gamma глутамилтрансферазы;
• Skin and hypodermic fabrics: seldom – heavy skin reactions, including violent damage of skin and desquamation;
• Others: very seldom – Stephens-Johnson and Layell's syndromes, beam reactions.

Special instructions

Treatment by Gemzar has to be carried out only under observation of the medical specialist having experience of performing antineoplastic therapy.

Before each administration of drug it is necessary to control quantity of leukocytes, granulocytes and thrombocytes in blood. In case of signs of oppression of function of marrow it is necessary to correct a dose or to suspend Gemzar's use.

It is regularly also necessary to inspect the patient and to carry out assessment of functions of his liver and kidneys. Administration of gemcitabine at cirrhosis, and also at alcoholism, hepatitis and metastasises in a liver in the anamnesis increases risk of development of a liver failure.

At increase in duration and frequency of infusion toxicity increases.

Researches on an occasion of influence of Gemzar on the speed of reactions and ability to concentration of attention were not conducted. However drug can cause drowsiness, especially in case of joint use of alcohol. Patients who during treatment test drowsiness should refrain from control of vehicles and work with difficult mechanisms.

Medicinal interaction

At Gemzar's use during performing radiation therapy or with an interval less than 7 days toxicity is noted.

During a course of treatment gemcitabine it is not necessary to enter live vaccines of yellow fever or other live vaccines as the risk of development of the general disease leading to a lethal outcome, especially at patients with immunosuppression increases.

Terms and storage conditions

To store at a temperature of 15-30 ºС. To protect from children.

Lyophilisate period of validity – 3 years. It is possible to store the solution prepared from it no more than 24 hours at a temperature of 15-30 ºС.