Gemita lyophilisate solution for infusion 200mg vials, 1pc

Composition

1 bottle contains:

Active ingredients:

gemcitabine hydrochloride is 227.72 mg, which corresponds to the gemcitabine content of 200 mg.

Auxiliary substances:

mannitol-200 mg,

sodium acetate trihydrate-12.5 mg,

hydrochloric acid-q. s. for pH correction,

sodium hydroxide-q. s. for pH correction.

In a bottle of 200 mg.

In a cardboard box 1 bottle.

Pharmacological action

Pharmacodynamics

antitumor drug, an antimetabolite of the pyrimidine analog group, suppresses DNA synthesis. It exhibits cyclospecificity, acting on cells in the S phase and at the boundary of the G1 and S phases. It is metabolized in the cell under the action of nucleoside kinases to active diphosphate and triphosphate nucleosides. Diphosphate nucleosides inhibit the action of ribonucleotide reductase (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.

The pharmacokinetics

of gemcitabine cmax (from 3.2 mcg / ml to 45.5 mcg / ml) are reached 5 minutes after the end of the infusion. Pharmacokinetic analysis of single-and multiple-dose studies shows that vd is significantly sex-dependent. The binding of gemcitabine to plasma proteins is insignificant.

In the body, gemcitabine is 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.

Gemcitabine is rapidly eliminated from the body by the kidneys, mainly as an inactive metabolite of 2’ – deoxy-2’,2’ – difluoruridine. Less than 10% of the administered intravenous dose is detected in the urine in the form of unchanged gemcitabine. Systemic clearance, which ranges from approximately 30 l / h / m2 to 90 l / h/m2, depends on age and gender.

T_1/2 ranges from 42 min to 94 min. If the recommended dosage regimen is followed, complete elimination 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.

Combination therapy with gemcitabine and paclitaxel. When gemcitabine and paclitaxel are co-administered, the pharmacokinetics of the drugs do not change.

Combination therapy with gemcitabine and carboplatin. When gemcitabine and carboplatin are co-administered, the pharmacokinetics of gemcitabine do not change.

Impaired renal function. Mild to moderate renal insufficiency (creatinine clearance 30-80 ml / min) does not significantly affect the pharmacokinetics of gemcitabine.

Indications

• Locally common or metastatic non-small cell lung cancer as first-line therapy in combination with cisplatin and as a monotherapy in elderly patients with functional status equal to 2 (on a scale ECOG-who);
• inoperable, locally recurrent or metastatic breast cancer after neoadjuvant and/or adjuvant therapy with the inclusion of anthracyclines in the absence of contraindications to their destination in a combination therapy with paclitaxel;
• locally common or metastatic urothelial carcinoma (bladder cancer, renal pelvis, ureter, urethra);
• locally advanced or widespread metastatic ovarian cancer as monotherapy or in combination with carboplatin in patients with disease progression after the first-line treatment based on platinum-containing drugs;
• locally common or metastatic pancreatic cancer;
• locally advanced or widespread metastatic cervical cancer.

Use during pregnancy and lactation

It is contraindicated to use the drug during pregnancy and lactation (breastfeeding).

Contraindications

• Pregnancy;
• breast-feeding period;
• children under 18 years of age (lack of sufficient data on efficacy and safety);
• hypersensitivity to the Active ingredient or to any of the excipients.

With caution: the drug should be prescribed for impaired liver and/or kidney function, suppression of bone marrow hematopoiesis (including on the background of concomitant radiation or chemotherapy), cardiovascular diseases, with metastatic liver damage, hepatitis, alcoholism, with simultaneous radiation therapy, acute infectious diseases of a viral, fungal or bacterial nature (including chickenpox, shingles).

Side effects

Side effects that occurred more frequently than in isolated cases are listed in accordance with the following gradation: :

• very common (> 10%);>
• common ( > 1% to >< 10%);
• infrequent ( > 0.1% to >< 1%);
• rare ( > 0.01% to >< 0.1%);
• very rare (

From the hematopoietic organs: very often – leukopenia, neutropenia, thrombocytopenia, anemia; often-febrile neutropenia; very rarely – thrombocytosis.

From the digestive system: very often-nausea, vomiting, increased activity of hepatic transaminases (AST, ALT), alkaline phosphatase; often – anorexia, diarrhea, constipation, stomatitis, increased bilirubin concentration; rarely-increased GGT activity.

From the urinary system: very often – hematuria and mild proteinuria; rarely-renal failure, clinical signs and symptoms similar to hemolytic-uremic syndrome (decreased hemoglobin, thrombocytopenia, increased concentration of bilirubin, creatinine, urea and/or LDH activity in the blood serum).

From the skin and subcutaneous tissues: very often-skin rashes accompanied by itching, alopecia; often-itching of the skin, increased sweating; rarely-skin ulceration, blistering; very rarely-severe skin reactions, including desquamation and bullous rashes.

From the respiratory system: 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, myocardial infarction, heart failure, arrhythmia.

From the nervous system: often-headache, increased drowsiness, insomnia.

Other: very often – flu-like syndrome, peripheral edema; often-fever, chills, asthenia, back pain, myalgia; infrequently-facial swelling; very rarely-anaphylactic reactions.

Interaction

Radiation therapy

Concomitant radiation therapy (simultaneously with the introduction of the drug Gemita or at intervals of: in this situation, the toxicity of treatment depends on many factors, including the dose of gemcitabine and the frequency of its use, the radiation dose, the method of radiation therapy, the nature of the irradiated tissue and its volume. Gemcitabine has been shown to have radiosensitizing activity. In one study where patients with non-small cell lung cancer received gemcitabine at a dose of 1000 mg / m2 for 6 consecutive weeks in combination with therapeutic radiation to the chest area, significant toxicity was noted in the form of severe and potentially life-threatening mucosal inflammation, mainly esophagitis and pneumonitis, especially in patients with a large volume of tissue irradiation (median volume of irradiated tissue 4795 cm3). Subsequent studies have shown that the combination of lower doses of gemcitabine and radiation therapy is better tolerated by patients and is characterized by a predictable toxicity profile. So, in one phase II study, patients with non-small cell lung cancer received radiation therapy at a dose of 60 Gy together with gemcitabine (600 mg/m2 4 times) and cisplatin (80 mg/m2 2 times) for 6 weeks.

Sequential therapy (break > 7 days): according to available data, use of gemcitabine more than 7 days before the start of radiation therapy or more than 7 days after its completion is not accompanied by an increase in toxicity, with the exception of skin damage associated with the use of chemotherapy after radiation. Gemcitabine treatment can be initiated 7 days after radiation exposure or after all acute radiation reactions have resolved.

Both concomitant and sequential use of gemcitabine and radiation therapy may cause radiation damage to the irradiated tissues (for example, esophagitis, colitis and pneumonitis).

Other types of interaction

When used concomitantly with live attenuated vaccines, it is possible to intensify the process of replication of the vaccine virus, increase its side/adverse effects and / or reduce the production of antibodies in the patient’s body in response to the introduction of the vaccine.

Immunosuppressants (including azathioprine, chlorambucil, corticosteroids, cyclophosphamide, cyclosporine, mercaptopurine) increase the risk of infection.

Compatibility studies of the drug Gemita have not been conducted. It is not recommended to mix Gemita with other medicinal products.

How to take it, course of use and dosage

Non-small cell lung cancer

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

In combination therapy with cisplatin, the recommended dose of the drug is 1250 mg / m2 on the 1st and 8th days of each 21-day cycle or 1000 mg / m2 on the 1st,8th and 15th days 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 the infusion of Hemita.

In combination therapy with carboplatin, the recommended dose of the drug is 1000 mg / m2 or 1200 mg/m2 on the 1st and 8th days of each 21-day cycle. Carboplatin is administered at an AUC of 5.0 mg / ml / min on day 1 of the cycle after Gemita infusion.

Breast cancer

In combination therapy as 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 administered after use of Gemita at a dose of 175 mg/m 2 in the 1st day of each 21-day cycle/drip for about 3 hours.

Urothelial cancer

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

In combination therapy, 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 Gemita on the 1st or 2nd day of each 28-day cycle.

Ovarian cancer

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

Pancreatic cancer

With monotherapy, the recommended dose of the drug is 1000 mg / m2 once a week for 7 weeks, followed by a one-week break. Then the drug is administered on the 1st,8th and 15th days of each 28-day cycle.

Cervical cancer (locally advanced or metastatic)

Combination therapy: for locally advanced cancer (neoadjuvant) and metastatic cancer, gemcitabine is administered at a dose of 1250 mg / m2 on days 1 and 8 of each 21-day cycle. Cisplatin is administered after use of the drug Gemita at a dose of 70 mg / m2 on the 1st day of the cycle against the background of hyperhydration.

In locally advanced cancer with simultaneous radiation therapy, Hemita is administered once a week for 6 weeks at a dose of 125 mg / m2, followed (immediately after the introduction of Hemita) by the introduction of cisplatin at a dose of 40 mg/m2 1-2 hours before the start of radiation therapy. Radiation therapy is performed for 28 fractions, in a single focal dose of 1.8 g,5 days a week to a total focal dose of 50.4 g.

Change in the dose of the drug due to the phenomenon of hematological toxicity

Beginning of the treatment cycle

Regardless of the indications, the number of platelets and granulocytes should be evaluated before each use of the drug. The condition for starting treatment is an absolute neutrophil count of at least 1,500 / µl and a platelet count of at least 100,000/µl.

If hematological toxicity develops during the treatment cycle, the dose of Hemita may be reduced or delayed in accordance with the following recommendations.

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

* – With an increase in the number of neutrophils up to 500/µl and platelets up to 50,000/µl, the use of Hemita can be continued as part of the cycle.

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

* – Treatment within the cycle is not resumed. The next use of the drug Gemita is carried out on the 1st day of the next cycle when the number of neutrophils reaches at least 1500/µl and platelets up to 100,000/µl.

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

* – Treatment within the cycle is not resumed. The next use of the drug Gemita is carried out on the 1st day of the next cycle when the number of neutrophils reaches at least 1500/µl and platelets up to 100,000/µl.

The dose of Gemita on the next cycle should be reduced by 25% for all indications in cases where the previous cycle was observed:

• reduced absolute neutrophil count < 500 / µl, lasting more than 5 days;
• reduced absolute neutrophil count < 100/µl, lasting more than 3 days;
• febrile neutropenia — – reduced platelet count < 25,000/µl;
• the cycle was delayed for more than 1 week due to hematological toxicity.

Method of use

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

Gemita should be used with caution in patients with hepatic insufficiency or impaired renal function, since there are no sufficient data on the use of the drug in this category of patients. Moderate or moderate renal insufficiency (glomerular filtration rate from 30 ml / min to 80 ml / min) does not significantly affect the pharmacokinetics of gemcitabine.

Gemita is well tolerated in elderly patients over 65 years of age. There are no specific recommendations for changing the dose of the drug for this population.

Gemita is not recommended for use in children under 18 years of age due to insufficient information on the safety and efficacy of the drug in this population.

Rules for preparing the solution for infusions

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

To prepare the infusion solution, the contents of the 200 mg vial are dissolved in at least 5 ml,1000 mg — in at least 25 ml, and 1400 mg — in at least 35 ml of 0.9% sodium chloride solution for injection. Each bottle is gently shaken until the lyophilizate is completely dissolved. The resulting solution should be transparent.

The maximum concentration of gemcitabine should not exceed 40 mg / ml. Solutions prepared with concentrations higher than 40 mg/ml may be accompanied by incomplete dissolution.

The prepared solution of the drug Hemita, containing the desired dose of the drug, 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, it is necessary to visually monitor the prepared solution for the presence of mechanical impurities and discoloration.

The prepared solution of Hemita is physically and chemically stable for 24 hours, provided that it is stored at a controlled room temperature (from 20°C to 25°C). From a microbiological point of view, the prepared solution should be used immediately. If the prepared solution was not used immediately and its preparation was carried out under controlled and validated aseptic conditions, the storage time is usually no more than 24 hours at room temperature (from 20° to 25°C).

Overdose

The antidote for gemcitabine is unknown.

When the drug Gemita was administered in doses up to 5700 mg/m2 intravenously for 30 minutes every 2 weeks, the level of toxicity of the treatment remained acceptable.

If an overdose of gemcitabine is suspected, the degree of cytopenia should be monitored and, if necessary, maintenance therapy should be prescribed.

Special instructions

Treatment with Hemita can only be carried out under the supervision of a doctor who has experience in antitumor chemotherapy.

Before each use of Hemita, it is necessary to determine the leukocyte formula and the number of platelets in the blood. If there are signs of bone marrow suppression caused by the drug, it is necessary to suspend treatment or adjust the dose.

It is necessary to conduct a regular examination of the patient and assess the function of the kidneys and liver.

use of Hemita in patients with liver metastases, a history of hepatitis and alcoholism, and cirrhosis of the liver increases the risk of developing liver failure.

If there are signs of developing adverse events from the respiratory system (for example, pulmonary edema, interstitial pneumonitis or respiratory distress syndrome in adults) during treatment with Hemita, treatment should be discontinued and appropriate therapy should be prescribed.

When the first signs of microangiopathic hemolytic anemia appear, such as a rapid decrease in hemoglobin with concomitant thrombocytopenia, an increase in serum bilirubin, creatinine, nitrogen, urea, or an increase in LDH activity, the drug should be discontinued. An increase in the duration of the infusion and the frequency of use leads to an increase in toxicity.

Depending on the degree of toxicity, the dose can be reduced during each cycle or with the start of a new cycle in stages.

Reliable methods of contraception should be used during treatment and for 6 months after the end of Hemita therapy. Men receiving Gemita are advised to resort to cryopreservation of sperm prior to treatment due to the risk of infertility due to the use of this drug.

Gemcitabine can be started after acute radiation reactions have resolved or no earlier than 7 days after the end of radiation therapy.

Gemcitabine in monotherapy or in combination with other antitumor agents is active in progressive small cell lung cancer, progressive testicular cancer and bile duct cancer.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

There are no data on the effect of Hemita therapy on the ability to drive a vehicle and work with mechanisms, however, some side effects of the drug, such as increased drowsiness, can negatively affect the ability to drive a car and perform potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions, which requires caution.

Form of production

Lyophilizate for preparation of solution for infusions.

Storage conditions

At a temperature not exceeding 25 °C (do not freeze)

Shelf life

2 years

Active ingredient

Gemcitabine

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as directed by your doctor

Indications

Cancer