Hematix

Hematix is an antineoplastic medicine. Included in the category of structural analogues of pyrimidine substance.

[1]

Indications of the hematix

It is used to eliminate the following pathologies:

• cancer affecting the bladder (in combination with cisplatin), metastatic or locally recurrent;
• cancer in the pancreas - adenocarcinoma of a metastatic or locally progressive nature;
• bronchogenic non-small cell carcinoma (gemcitabine with cisplatin) is the first choice drug for persons with a metastatic or locally progressive form of the disease. For monotherapy, the drug is used for the elderly, as well as individuals with a 2nd functional status;
• ovarian carcinoma (drug in combination with carboplatin) - elimination of metastatic epithelial or locally progressive form of pathology. Used in patients with relapse of the epithelial form of cancer after the remission phase, which is at least six months after the previous treatment of the 1st line with the help of platinum drugs;
• Breast cancer (Hematix with paclitaxel) is a therapy for people with metastatic or locally recurrent inoperable disease after chemotherapy (adjuvant or neoadjuvant). During the procedures of previous chemotherapy, the patient should be given anthracycline (in the absence of contraindications);
• cholangiocarcinoma.

[2], [3], [4], [5]

Release form

The release occurs in the form of a powder from which an infusion solution is made. Inside the pack - 1 bottle with lyophilizate.

Pharmacodynamics

Gemcitabine is an antitumor substance with cytotoxic properties, which are caused by a slowing down of DNA binding processes. Metabolism of drugs is carried out inside the cell with the subsequent transformation into nucleosides (di- and triphosphate).

First, the nucleosides of a diphosphate nature formed as a result of this process slow down the activity of ribonucleotide reductase. This enzyme is a catalyst for reactions that lead to the formation of deoxynucleoside triphosphate, necessary for DNA binding, inside the cells. As a result, their indices inside the cell are reduced.

Secondly, the triphosphate-type nucleosides formed during the metabolism of LS enter into active competition for entry into the DNA chain, and in addition are able to be embedded in RNA. As a result of the integration of intracellular products of drug metabolism into the chain of DNA, an additional nucleotide is added to its increasing chains, resulting in a complete slowdown in the subsequent binding of DNA, as well as programmed cell destruction.

[6], [7]

Pharmacokinetics

With a one-time infusion of the drug in a dose of 1 g / m ² (the procedure lasts for half an hour) the peak values of gemcitabine inside the blood plasma are noted 3-15 minutes after the completion of the procedure. Protein synthesis inside the plasma is extremely low. The distribution volume of LS inside the tissues is also small and equal to an average of 11 l / m ².

Gradual metabolism of Hematix occurs inside the hepatic cells, and also inside the blood and other body tissues with the help of the enzyme cytidine deaminase. As a result, an inactive uracil product of metabolism is formed.

During intracellular metabolism, active nucleosides of diphosphate and triphosphate type are formed. Their indices inside the cells increase in proportion to the level of the drug inside the blood plasma. After reaching the equilibrium values of gemcitabine inside the plasma - above 5 μg / ml - the level of nucleosides inside the cells no longer increases.

Half an hour infusion of drugs in a dose of 1 g / m ² leads to the production of plasma values of the drug, about 5-4 μg / ml. This level lasts for 90 minutes, which allows to provide the necessary intracellular parameters of nucleosides. In the urine with blood plasma intracellular metabolic products are not observed.

The excretion of the drug mainly occurs in the form of the uracil product of metabolism (most of it with urine, and even less 1% with feces). Only 1% of the dosage is unchanged. The elimination half-life is approximately 17 minutes. After multiple use of drugs, this indicator is slightly increased.

The values of the clearance in women are slightly lower than those of men. It is believed that with a weakened activity of the kidneys inside the body can accumulate an inactive product of metabolism.

[8], [9]

Dosing and administration

Gemcitabine can only be used by a doctor with experience in performing oncological chemotherapy procedures.

Adults.

Cancer in the bladder area.

Treatment is combined. You should enter a dose of 1 g / m ² gemcitabine - intravenous infusion, lasting half an hour. This dosage should be administered on the 1st, 8th, and also the 15th day of each of the 28 day cycles performed, in conjunction with the cisplatin substance. It is administered at a dosage of 70 mg / m ² on the first day after the administration of gemcitabine or on the 2nd day of each new cycle. After this, you need to repeat this cycle (4 weeks). Reduce the portion size with each subsequent cycle or during a single cycle is allowed in view of the level of toxicity, which during the therapy is exposed to the patient.

Cancer in the pancreas.

Gemcitabine infusion is administered in a dose of 1 g / m ², for half an hour, once a week, for 7 weeks, after which a 7-day break is required. New cycles include injections, performed once a week, for 3 weeks. Each 4th week is a break between cycles. Reduce the size of a portion with each subsequent cycle, or during a particular cycle, is allowed, taking into account the toxicity indicators on the patient.

Bronchogenic carcinoma of non-small cell type.

Monotherapeutic method.

The size of the required portion of gemcitabine is 1 g / m ². Dosage should be administered with an infusion procedure lasting half an hour, once a week, in the period of 3 weeks, at the end of which a 7-day interval is needed. Then this 4-week cycle should be repeated. Lowering of dosage sizes with each new cycle or within a single cycle is possible taking into account the toxic level to which the treating person is exposed.

Combined method.

The recommended portion size is 1250 mg / m ², it is administered by the IV infusion method, for half an hour - on the 1st, and also on the 8th day of each cycle, which duration is 21 days. The dosage size is allowed to be lowered with each new cycle or during a single cycle, taking into account the level of toxicity to the patient. Cisplatin is then administered in a portion of 75-100 mg / m ², once a period of 3 weeks of the treatment cycle.

Breast cancer.

Combined therapy is used. Hematix together with paclitaxel is used according to the following scheme: palitaxel in a dosage of 175 mg / m ² is administered on the 1st day by a 3-hour infusion and then gemcitabine is administered in a dose of 1250 mg / m ², by a half-hour infusion, on the 1st, as well as the 8th days of each individual cycle, lasting 21 days. The size of the dosage is allowed to be reduced with each new cycle or during a separate cycle, taking into account the level of toxic effect exerted on the patient. Before the first procedure for administering the above drug combination, the absolute number of granulocytes in the patient should be less than 1500 (x10 ⁶ / l).

Carcinoma of the ovaries.

The drug is used in combination with carboplatin. It is injected in a portion of 1 g / m ², using a half-hour introduction on the first, and also the 8th day of the 21-day cycle. On the first day of the treatment cycle, after the use of gemcitabine, carboplatin is used - in a dose that provides an AUC level of 4 mg / ml / minute. The dosage size of the drug can be lowered with each subsequent cycle, or during a single cycle, taking into account the toxicity indicators on the patient.

Cholangiocarcinoma.

Monotherapeutic method.

The recommended amount of Hematix is 1 g / m ²; it is required to enter for half an hour. This infusion is performed once a week for a period of 3 consecutive weeks, followed by a 7-day interval. Then this cycle must be repeated. Reduction of dosage with each subsequent cycle or during a single cycle is carried out taking into account the severity of the toxic effect exerted on the patient.

Combined method of therapy.

Scheme of drug use with cisplatin: the latter is administered through infusion at a dosage of 70 mg / m ² on the first day of the treatment cycle, after which gemcitabine is used in a dose of 1250 mg / m ² (on the first and also on the 8th day of each from cycles lasting 21 days) - through a half-hour infusion. Such a 21-day cycle is required to be repeated. The reduction in the size of a portion with each new cycle or during a single cycle can be made taking into account the severity of the toxic effect to which the patient is exposed.

Persons with kidney / liver failure.

It is necessary to carefully prescribe the drug to people in this category, because clinical tests have not demonstrated the necessary amount of data to allow the calculation of exact dosages for these patients.

The scheme of manufacturing the infusion solution.

To restore the sterility of gemcitabine lyophilizate, only 1 solvent is suitable: 0.9% injection of sodium chloride (9 mg / ml, preservative-free). Given the solubility of the substance, the peak value of the drug after the procedure of recovery is 40 mg / ml. If the restoration is performed to levels exceeding 40 mg / ml, incomplete dissolution of the powder may result, which can not be tolerated.

It is necessary to apply the aseptic method during the dissolution of the drug element with its subsequent dilution.

To perform the dissolution, it is required to add a bottle containing 0.2 g of the drug, 5 ml of sodium chloride solution inside the vial. After the dilution procedure, the total volume indicator is 5.26 ml. As a result, the concentration of the finished solution is 38 mg / ml (taking into account the replacement volume of the lyophilizate). To dissolve the mixture, you need to shake the bottle. The finished medicinal substance looks like a colorless transparent liquid of a pale yellow hue.

Before starting the infusion procedure, it is required to visually inspect the resulting solution in order to detect the possible presence in it of various mechanical impurities or a change in hue. If such manifestations are found, the administration of this solution should be discarded.

Unused powder together with waste materials must be destroyed.

[13]

Use of the hematix during pregnancy

Pregnancy.

Adequate information regarding the use of gemcitabine in pregnant women - no. It is prohibited to use Hematix during this period, except in cases of extreme necessity.

When pregnancy occurs during therapy with gemcitabine, you should inform your doctor about it.

Lactation.

There is no information as to whether the drug is excreted in human milk, so it is not possible to exclude the development of negative symptoms in breast-fed infants. Because of this, it is required to refuse breastfeeding while using gemcitabine.

Contraindications

The main contraindication is the presence of high sensitivity with respect to the active element or any of the auxiliary components of the medication.

[10], [11],

Side effects of the hematix

The use of a therapeutic agent can cause the appearance of side effects:

• problems with hematopoietic processes: suppression of bone marrow hematopoiesis (development of leuko-, thrombocyto- or neutropenia, as well as anemia). Single-onset neutropenic fever or thrombocytosis;
• Immune disorders: development of anaphylactoid manifestations;
• problems with metabolic processes: the development of anorexia;
• disorders of digestive activity: the emergence of diarrhea, vomiting, constipation, nausea, and in addition stomatitis and ulcers in the oral cavity. Also, colitis is of an ischemic nature and an increase in the values of liver enzymes within the blood serum;
• lesions affecting the hepatobiliary system: an increase in the parameters of liver enzymes (ALT and AST), and in addition GGT, bilirubin and alkaline phosphatase. May develop severe hepatotoxicity, leading to liver failure with a fatal outcome;
• disturbances in the function of the urination system: kidney failure, hematuria and a moderate degree of proteinuria. Individual signs similar to HUS are observed. Problems with the kidneys can be incurable even after stopping therapy (hemodialysis may be necessary). Use of drugs is required to be completed after the first symptoms of MHA appear - a sharp decrease in hemoglobin values against which thrombocytopenia appears, as well as an increase in urea, bilirubin, LDH, or creatinine within the blood serum;
• damage to the subcutaneous layers and skin surface: skin rash allergic genesis, against which often there is erythema, pruritus, alopecia and hyperhidrosis. Severe forms of skin symptoms are noted, such as bullous rash, desquamation, ulcers, peeling, vesicles, as well as Stevens-Johnson syndrome and TEN;
• violations of respiratory activity: cough, dyspnea (usually in mild form, disappears on its own) and runny nose. Occasionally there are spasms of bronchi (often mild to transient, although sometimes there is a need for parenteral therapy), fibrosing alveolitis, pulmonary edema and hyaline membrane disease in adults. If the patient has such signs, you need to stop therapy;
• disorders of CCC activity: peripheral puffiness. There is a single myocardial infarction, a decrease in blood pressure, various arrhythmias (often of a supraventricular nature), and heart failure. There may also be clinical symptoms of gangrene and peripheral vasculitis, and besides this, capillary leakage syndrome;
• reactions from the NA: development of insomnia, sensation of drowsiness and headaches, a disorder of the circulatory processes inside the brain, and also SOE;
• lesions affecting the activity of ODA: myalgia and pain in the back;
• indications of laboratory tests: an increase in the values of creatinine, GGT, bilirubin, LDH, and in addition urea and AF in the blood serum;
• systemic disorders: influenza-like manifestations, observed most often - headaches, fever, myalgia, chills, loss of appetite and asthenia. In addition, there have been reports of hyperhidrosis, a feeling of malaise, a runny nose with a cough and problems with sleep;
• complications, intoxication and damage arising during the procedure: radiation poisoning (with the concomitant conduct of radiotherapy), the development of "radiation memory";
• signs of allergy: occasionally there are anaphylactic symptoms.

Moderate skin manifestations may occur at the site of administration. Puffiness (sometimes peripheral) also develops, in some cases - on the face; they pass after the end of therapy.

[12]

Overdose

Gemcitabine does not have an antidote that can be used in an overdose.

Clinically acceptable toxicity level is noted when using portions of not more than 5.7 g / m ², which are administered through infusions for half an hour with a frequency of 1 time / 2 weeks.

If suspected of intoxication is required to monitor the patient's health and conduct the necessary laboratory blood tests. In addition, if necessary, symptomatic measures can be prescribed.

[14], [15]

Interactions with other drugs

Specific tests regarding the drug drug interaction were not performed.

Radiotherapy.

When treatment is performed together with radiotherapy (or less than a week after it), toxicity develops, which is caused by treatment with different methods. The development of this disorder is determined by the presence of a variety of factors, including the frequency of infusions, the size of the portion of Hematix, the scheme according to which radiotherapy is performed, and also the instruments used, the volume and area of irradiation.

Tests demonstrated that gemcitabine has a radiosensitive activity. At his appointment in a dose of 1 g / m ²  for 1.5 months in combination with medical irradiation of the sternum in persons with bronchogenic carcinoma of non-small cell type, there was very strong toxicity in the form of severe pneumonitis, esophagitis, and also mucositis, potentially endangering human life (especially in those people who received radiotherapy in significant amounts - with medication therapy, the volume of which is 4.795 cm ³ ).

With non-small cell form of bronchogenic carcinoma, it is acceptable to use the drug in smaller portions, taking into account the toxicity provided by radiotherapeutic procedures. Irradiation of the sternum in a dosage of 66 Gy was performed together with the use of a medicament (0.6 g / m ², 4 infusions), and cisplatin (a dose of 80 mg / m ², 2 infusions) for 1.5 months. The optimal and safe mode of using medicines with medicinal portions of irradiation for any type of tumors has not yet been selected.

If there was an incompatibility with radiotherapy (more than 7 days before or after the procedure), the increase in toxic properties after the use of gemcitabine during the analysis of the information was not revealed (except for the situation with the development of "radiation memory"). This information demonstrates that administration of drugs is permitted after the disappearance of symptoms of acute complications of irradiating procedures - at least 1 week after the radiotherapy.

There is evidence of damage to certain tissues in irradiated areas after radiotherapy (development of colitis, esophagitis, or pneumonitis) when used with or without Gematics.

Other.

The combination of the drug with weakened live vaccines (including amarillosis vaccine) is prohibited due to the risk of developing a common pathology that can become fatal - this is especially true of people with immunosuppression.

[16], [17], [18]

Storage conditions

Hematics should be kept out of the reach of small children. Do not freeze the medicament. The temperature values are not more than 25 ° C.

[19]

Shelf life

Hematix can be used for 2 years after the manufacture of the therapeutic agent.

[20]

Application for children

Children prescribe a drug is not recommended - because of information about its safety and effectiveness in this category of patients are not enough.

[21], [22], [23]

Analogues

Hematics has the following drug analogues - Wizgem and Gemzar with Gembicin, and in addition Gemcitabine-Ebwe, Gemcitabine-Vista with Gembitacin Medak and Gembitacin-Farmex with Gembitacin-Teva. It also includes Onkogem and Gercizar with Strigem, and in addition Dercin with Cytogem, Gemcitera with Tolgecitum and Onegin with Gemcitabine-Aktavis.

[24], [25], [26], [27], [28]