Gemcitabine-Teva lyophilisate solution concentrate for infusion 1000mg vials, 1pc

Composition

1 bottle contains:

Active ingredient:

gemcitabine hydrochloride anhydrous 1140 mg in terms of gemcitabine-1000 mg;

auxiliary components:  mannitol, sodium acetate trihydrate, hydrochloric acid and / or sodium hydroxide for pH.

Pharmacological action

Pharmacotherapy group: Antitumor agent, antimetabolit ATH: L. 01. B. C. 05 Gemcitabine Pharmacodynamics :

Gemcitabine is an antimetabolite of the pyrimidine analog group. The drug suppresses DNA synthesis. It exhibits cyclospecificity, acting on cells in the S and G1/S phases. It is metabolized in the cell by nucleoside kinases to form active diphosphate and triphosphate nucleosides. Diphosphate nucleosides inhibit ribonucleotide reductase, which is the only enzyme that catalyzes the formation of deoxynucleoside triphosphates necessary for DNA synthesis. Triphosphate nucleosides are able to integrate into the DNA chain (to a lesser extent, RNA), which leads to the termination of further DNA synthesis and programmed cell lysis (apoptosis).

Gemcitabine is also a strong radiosensitizing agent, even at concentrations lower than cytotoxic ones.

Pharmacokinetics:

It is metabolized in liver, kidney, and blood cells under the action of the enzyme cytidine deaminase in stages, until the formation of an inactive metabolite of 2′ – deoxy-2′,2′ – difluoruridine. The volume of distribution largely depends on the duration of the infusion and gender. Plasma protein binding is low (less than 10%). Systemic clearance, which ranges from approximately 30 l / h / m2 to 90 l/h/m2, depends on age and gender (women have 25% less clearance than men; gemcitabine clearance decreases with age). The elimination half-life ranges from 42 minutes to 94 minutes. It is mainly excreted by the kidneys in the form of an inactive metabolite of 2’ – deoxy-22’ – difluoruridine (89%), as well as in unchanged form (less than 10%); less than 1% – with feces.

With reduced kidney function, an inactive metabolite can accumulate in the body.

Indications

– Non-small cell lung cancer

-Pancreatic cancer

– Bladder cancer

-Breast cancer

-Locally advanced or metastatic cervical cancer

Gemcitabine alone or in combination with other antitumor agents is also active in ovarian cancer, locally advanced small cell lung cancer, and locally advanced refractory testicular cancer.

Contraindications

-hypersensitivity to gemcitabine or other components of the drug

-pregnancy and lactation

With caution: In case of impaired liver and/or kidney function, suppression of bone marrow hematopoiesis (including on the background of concomitant radiation or chemotherapy), with simultaneous radiation therapy, acute infectious diseases of a viral, fungal or bacterial nature (including chickenpox, shingles).

Side effects

Adverse reactions classified in accordance with the recommendations of the world health organization: very often – at least 10%; often – not less than 1% but < 10%; infrequently – no more than 0.1% but < 1%; rarely – not less than 0.01%, but less than 0.1%; very rarely (including isolated cases) – less than 0.01%.

From the side of hematopoietic organs:  very often – leukopenia, neutropenia, thrombocytopenia, anemia; often-febrile neutropenia; very rarely-thrombocytosis, microangiopathic hemolytic anemia (rapid decrease in hemoglobin with concomitant thrombocytopenia, increased serum concentrations of bilirubin, creatinine, urea nitrogen or increased activity of lactate dehydrogenase(LDH)).

From the digestive system:  very often-nausea, vomiting, increased activity of “hepatic” transaminases, alkaline phosphatase; often – anorexia, diarrhea, constipation, stomatitis, ulceration of the oral mucosa, increased bilirubin concentration; rarely – increased activity of gamma-glutamine transferase; frequency cannot be estimated on the basis of available data – toxic liver damage, including liver failure, ischemic colitis.

From the urinary system:  very common – hematuria and mild proteinuria; frequency cannot be estimated on the basis of available data-acute renal failure, hemolytic-uremic syndrome (microangiopathic hemolytic anemia, platelet hepenia and acute renal failure).

From the side of the skin and skin appendages:  very often-alopecia; rarely-peeling, blistering and ulceration, excessive sweating; very rarely-severe desquamation of the skin, bullous skin rash.

Respiratory system disorders:  very often-shortness of breath; often-cough, rhinitis; infrequently-bronchospasm, interstitial pneumonitis, pulmonary edema; rarely-acute respiratory distress syndrome.

From the cardiovascular system:  rarely-decreased blood pressure (BP), myocardial infarction; frequency cannot be estimated on the basis of available data-heart failure, arrhythmia (mainly supraventricular).

Nervous system disorders:  often – headache, drowsiness, insomnia, paresthesia; rarely-cerebral circulation disorders, including stroke.

Allergic reactions:  very common-skin rash accompanied by pruritus; very rare-anaphylactic reactions; frequency cannot be estimated on the basis of available data-Lyell’s syndrome, Stevens-Johnson syndrome.

From the musculoskeletal system:  often – back pain, myalgia.

Other services:  very often-feeling unwell, flu-like syndrome, peripheral edema (usually disappear after stopping treatment); often-fever, chills, asthenia; infrequently-swelling of the face; rarely-reaction at the injection site; very rarely peripheral vasculitis, gangrene.

Interaction

Gemcitabine Teva has a radiosensitizing effect, so when using the drug against the background of radiation therapy, you can expect increased radiation reactions.

Reduces the production of antibodies and increases side effects with the simultaneous use of inactivated or live viral vaccines (the interval between the use of drugs should be from 3 to 12 months).

How to take, course of use and dosage

Intravenous drip for 30 minutes.

Non-small cell lung cancer

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

Combination therapy with cisplatin: the recommended dose 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.

Cisplatin is administered at a dose of 70 mg / m2 on the 1st day of the cycle against the background of water load after gemcitabine infusion.

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

Breast cancer

Combination therapy: the therapy 1st line with the progression of the disease after neoadjuvant therapy, including anthracyclines, the recommended dose is 1250 mg/m 2 in the 1st and 8th days in combination with paclitaxel, which is introduced after the introduction of gemcitabine at a dose of 175 mg/m 2 in the 1st day of each 21-day cycle/drip for about 3 hours.

Urothelial cancer

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

Combination therapy: the recommended dose 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 gemcitabine infusion on the 1st or 2nd day of each 28-day cycle.

Ovarian cancer

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

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

Pancreatic cancer

Monotherapy: the recommended dose is 1000 mg / m2 once a week for 7 weeks, followed by a one-week break. Gemcitabine-Teva is then administered on days 1,8, and 15 of each 28-day cycle.

If hematological toxicity develops during the treatment cycle, the dose of Gemcitabine-Teva may be reduced or delayed in accordance with the following recommendations:

Modification of the dose of gemcitabine used in monotherapy or in combination with cisplatin in the treatment of bladder cancer, non-small cell lung cancer and pancreatic cancer

* If the number of neutrophils increases to 500/µl and platelets increases to 50,000/µl, gemcitabine may be continued as part of the cycle.

Modification of the dose of gemcitabine used in combination with paclitaxel in the treatment of breast cancer

* Treatment within the cycle is not resumed. The next use of gemcitabine is performed on the 1st day of the next cycle when the APN is restored to at least 1500 / µl and the platelet count to 100,000/µl.

Modification of the dose of gemcitabine used in combination with carboplatin in the treatment of ovarian cancer

* Treatment within the cycle is not resumed. The next use of gemcitabine is performed on the 1st day of the next cycle when the APN reaches at least 1500 / µl and the platelet count reaches 100,000/µl. The dose of gemcitabine on the next cycle should be reduced by 25% for all indications in cases where the previous cycle was observed:

• reduced APN less than 500 / µl, lasting more than 5 days,

• reduced APN less than 100/µl, lasting more than 3 days,

• febrile neutropenia,

• reduced platelet count less than 25,000/µl,

• the cycle was delayed for more than 1 week due to hematological toxicity. Method of use

Infusion of Gemcitabine-Teva is usually well tolerated by patients and can be performed on an outpatient basis. In case of extravasation, the infusion is stopped and Gemcitabine-Teva is reintroduced into another vein. After use of Gemcitabine-Teva, the patient should be monitored for some time.

Patients with impaired liver and kidney function: Gemcitabine-Teva should be used with caution in patients with hepatic insufficiency or impaired renal function, since there are no sufficient data on the use of gemcitabine in this category of patients. Moderate or moderate renal insufficiency (glomerular filtration rate from 30 ml / min to 80 ml / min) It has no significant effect on the pharmacokinetics of gemcitabine.

Elderly patients over 65 years of age: hem – cytabine is well tolerated in patients over 65 years of age. There are no specific recommendations for changing the dose of Gemcitabine-Teva in this population.

Preparation of the infusion solution

Only 0.9% sodium chloride solution without preservatives is used as a solvent.

To prepare the infusion solution, the required amount of 0.9% sodium chloride solution for injection is slowly introduced into the vial (not less than the amount indicated in the table below) and the vial is gently shaken until the contents are completely dissolved.

The resulting solution should be transparent.

The maximum concentration of the reduced gemcitabine solution should not exceed 38 mg / ml, since at higher concentrations, incomplete dissolution of the lyophilizate is possible.

The prepared solution containing the required dose of gemcitabine is diluted before use with 0.9% sodium chloride solution for injection in an amount sufficient for a 30-minute intravenous infusion.

Before parenteral use of the Gemcitabine-Teva solution, make sure that there are no undissolved particles and color changes in the solution. The prepared solution of Gemcitabine-Teva is intended for single use only.

Any unused Gemcitabine-Teva solution should be disposed of.

Overdose

Symptoms: myelosuppression, paresthesia, severe skin rash.

Treatment: there is no specific antidote. If an overdose is suspected, the patient should be under constant medical supervision, including counting the blood formula; if necessary, symptomatic treatment is carried out.

Special instructions

Treatment with Gemcitabine Teva should only be carried out under the supervision of a doctor who has experience in the use of antitumor chemotherapy.

Before each use of the drug, it is necessary to monitor the number of platelets, white blood cells and neutrophils in the blood. If there are signs of bone marrow suppression, treatment should be suspended or the dose adjusted. Kidney and liver function should be evaluated periodically.

An increase in the duration of the infusion and the frequency of infusions leads to an increase in toxicity.

use of Gemcitabine Teva to patients with liver metastases, a history of hepatitis and alcoholism, and cirrhosis increases the risk of developing liver failure.

If the first signs of hemolytic-uremic syndrome occur, treatment with Gemcitabine Teva should be discontinued.

Patients with lung cancer or lung metastases have an increased risk of side effects from the respiratory system.

When the first signs of pneumonitis or infiltrates in the lungs appear, Gemcitabine Teva treatment should be discontinued.

Gemcitabine Teva can be started after resolution of acute radiation reactions or ns earlier than 7 days after the end of radiation therapy.

Women and men should use reliable methods of contraception during Gemcitabine Teva treatment and for at least 6 months thereafter.

Influence on the ability to drive vehicles and mechanisms:During treatment, caution should be exercised when driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

List B.

Lyophilizate – at a temperature not exceeding 30 °C.

The prepared solution – at a temperature not exceeding 25°C.

Keep out of the reach of children!

Shelf

life is 2 years.

Prepared solution – 6 hours.

Do not use after the expiration date indicated on the package.

Active ingredient

Gemcitabine

Conditions of release from pharmacies

By prescription

Dosage form

lyophilizate for solution preparation