Hematix

Hematix is an antineoplastic drug. It belongs to the category of structural analogs of the substance pyrimidine.

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Indications Hematixa

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;
• non-small cell bronchogenic carcinoma (gemcitabine together with cisplatin) is the drug of first choice for people with metastatic or locally progressive form of the disease. For monotherapy, the drug is used in elderly people, as well as in people with the 2nd functional status;
• ovarian carcinoma (a drug in combination with carboplatin) – elimination of metastatic epithelial or locally progressive form of pathology. It is used in patients with relapse of the epithelial form of cancer after the end of the remission stage, which is at least six months after the previous first-line treatment with platinum drugs;
• breast cancer (Hematix with paclitaxel) – therapy for people with metastatic or locally recurrent inoperable disease after a course of chemotherapy (adjuvant or neoadjuvant). During the previous chemotherapy procedures, the patient should be administered anthracycline (unless contraindicated);
• cholangiocarcinoma.

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Release form

It is released in the form of a powder, from which an infusion solution is made. Inside the pack there is 1 bottle with lyophilisate.

Pharmacodynamics

Gemcitabine is an antitumor substance with cytotoxic properties due to the slowing down of DNA binding processes. The drug is metabolized inside the cell with subsequent conversion into nucleosides (di- and triphosphate).

Firstly, the diphosphate nucleosides 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 inside cells, which is necessary for DNA binding. As a result, their indicators inside the cell decrease.

Secondly, the triphosphate nucleosides formed during drug metabolism enter into active competition for inclusion in the DNA chain, and in addition to this, they are capable of being integrated into RNA. As a result of the integration of intracellular products of drug metabolism into the DNA chain, an additional nucleotide is added to its growing chains, as a result of which a complete slowdown of subsequent DNA binding develops, as well as programmed cell destruction.

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Pharmacokinetics

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

The stepwise metabolism of Hematix occurs within liver cells, as well as within the blood and other tissues of the body with the help of the enzyme cytidine deaminase. As a result, an inactive uracil metabolic product is formed.

During intracellular metabolism, active nucleosides of the diphosphate and triphosphate type are formed. Their intracellular levels increase proportionally to the drug level in the blood plasma. After reaching equilibrium values of gemcitabine in the plasma – above 5 mcg/ml – the intracellular nucleoside level no longer increases.

A half-hour infusion of the drug in a 1 g/ ^m2 dose results in plasma drug values of about 5-4 μg/ml. This level is maintained for 90 minutes, which allows for the necessary intracellular nucleoside values. Intracellular metabolic products are not observed in urine with blood plasma.

The excretion of the drug occurs mainly in the form of uracil metabolic product (most of it in urine, and even less than 1% in feces). Only 1% of the dosage is excreted unchanged. The half-life is approximately 17 minutes. After repeated use of the drug, this indicator increases slightly.

Clearance values in women are slightly lower than in men. It is believed that with weakened kidney activity, an inactive metabolic product may accumulate inside the body.

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Dosing and administration

Gemcitabine should only be used by a doctor who has experience in performing cancer chemotherapy procedures.

Adults.

Cancer in the bladder area.

The treatment is combined. A dose of 1 g/m2 of gemcitabine should be administered ^– intravenous infusion lasting half an hour. This dosage should be administered on the 1st, 8th, and 15th days of each of the 28-day cycles, in combination with cisplatin. It is administered at a dosage of 70 mg/m2 ^on the 1st day after the administration of gemcitabine or on the 2nd day of each new cycle. After this, this cycle must be repeated (4 weeks). Reducing the dose size with each subsequent cycle or during a separate cycle is allowed, taking into account the level of toxicity to which the patient is exposed during therapy.

Cancer in the pancreas area.

Gemcitabine infusion is administered in doses of 1 g/ ^m2, over half an hour, once a week, for 7 weeks, followed by a 7-day break. New cycles include injections administered once a week, for 3 weeks. Every 4th week is a break between cycles. Reducing the dose size with each subsequent cycle or during a single cycle is allowed, taking into account the toxicity indicators exerted on the patient.

Non-small cell bronchogenic carcinoma.

Monotherapeutic method.

The required dose of gemcitabine is 1 g/m2 ^. The dosage should be administered by a half-hour infusion once a week for a period of 3 weeks, after which a 7-day interval is required. This 4-week cycle should then be repeated. A reduction in the dosage with each new cycle or during a single cycle is possible taking into account the toxic level to which the person being treated is exposed.

Combined method.

The recommended dose is 1250 mg/ ^m2, administered intravenously over half an hour on days 1 and 8 of each 21-day cycle. The dose may be reduced with each new cycle or within a single cycle, taking into account the level of toxicity to the patient. Cisplatin is administered in a dose of 75-100 mg/m2 ^, once during a 3-week treatment cycle.

Breast cancer.

Combination therapy is used. Hematix together with paclitaxel is used according to the following scheme: paclitaxel at a dosage of 175 mg/m2 ^is administered on the 1st day by a 3-hour infusion, and then gemcitabine is administered in a portion of 1250 mg/ ^m2, by a half-hour infusion, on the 1st and 8th days of each individual cycle, lasting 21 days. The dosage may be reduced with each new cycle or during a separate cycle, taking into account the level of toxic effects on the patient. Before the 1st procedure of administration of the above-mentioned drug combination, the absolute number of granulocytes in the patient should be less than 1500 (x10 ⁶ /l).

Ovarian carcinoma.

The drug is used in combination with carboplatin. It is administered in a dose of 1 g/ ^m2, by half-hourly administration on the 1st and 8th days of a 21-day cycle. On the 1st day of the treatment cycle, after using gemcitabine, carboplatin is used - in a dose that provides an AUC level of 4 mg/ml/minute. The dosage of the drug can be reduced with each subsequent cycle or during a separate cycle, taking into account the toxicity indicators exerted on the patient.

Cholangiocarcinoma.

Monotherapeutic method.

The recommended dose of Hematix is 1 g/ ^m2; it should be administered over half an hour. This infusion is administered once a week for 3 consecutive weeks, followed by a 7-day interval. This cycle should then be repeated. The dosage is reduced with each subsequent cycle or during a single cycle, taking into account the severity of the toxic effect on the patient.

Combination therapy method.

The scheme of using the drug together with cisplatin: the latter is administered via infusion at a dosage of 70 mg/ ^m2 on the 1st day of the treatment cycle, after which gemcitabine is used in a portion of 1250 mg/m2 ⁽ on the 1st and 8th days of each of the 21-day cycles) - via a half-hour infusion. Such a 21-day cycle must be repeated. A decrease in the portion size with each new cycle or during a separate cycle can be made taking into account the severity of the toxic effect to which the patient is exposed.

Persons with renal/liver impairment.

Caution is required when prescribing the drug to people in this category, because clinical trials have not demonstrated the necessary amount of data to allow calculation of accurate dosages for these patients.

Scheme for the production of infusion medicinal solution.

Only one solvent is suitable for restoring the sterility of gemcitabine lyophilisate – 0.9% sodium chloride injection medicinal solution (9 mg/ml; preservative-free). Given the solubility of the substance, the peak value of the drug after the reconstitution procedure is 40 mg/ml. When reconstituting to values exceeding 40 mg/ml, incomplete dissolution of the powder may follow, which should not be allowed.

It is necessary to use an aseptic method during the dissolution of the medicinal element with its subsequent dilution.

To perform dissolution, it is necessary to add 5 ml of sodium chloride solution into the bottle containing 0.2 g of the medicine. After the dilution procedure, the total volume 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 lyophilisate). To dissolve the mixture, it is necessary 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 necessary to visually inspect the resulting solution to identify the possible presence of various mechanical impurities or a change in color. If such manifestations are detected, you should refuse to administer this solution.

Unused powder must be destroyed along with waste materials.

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Use Hematixa during pregnancy

Pregnancy.

There is no adequate information regarding the use of gemcitabine in pregnant women. The use of Hematix during this period is prohibited, except in cases of extreme necessity.

If you become pregnant while taking gemcitabine, you should tell your doctor.

Lactation.

There is no information on whether the drug is excreted in breast milk, so the development of negative symptoms in breastfed infants cannot be ruled out. Because of this, breastfeeding should be discontinued while using gemcitabine.

Contraindications

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

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Side effects Hematixa

The use of the therapeutic agent may cause the appearance of side effects:

• problems with hematopoiesis: suppression of bone marrow hematopoiesis (development of leuko-, thrombocyto- or neutropenia, as well as anemia). Neutropenic fever or thrombocytosis is observed sporadically;
• immune disorders: development of anaphylactoid manifestations;
• problems with metabolic processes: development of anorexia;
• digestive disorders: occurrence of diarrhea, vomiting, constipation, nausea, and in addition to this, stomatitis and ulcers in the oral cavity. Colitis of an ischemic nature and an increase in the values of liver enzymes in the blood serum are also observed;
• lesions affecting the hepatobiliary system: increased liver enzyme levels (ALT and AST), as well as GGT, bilirubin and alkaline phosphatase. Severe hepatotoxicity may develop, leading to fatal liver failure;
• urinary system dysfunction: renal failure, hematuria and moderate proteinuria. Signs similar to HUS are observed sporadically. Kidney problems may be incurable even after stopping therapy (hemodialysis may be required). The use of the drug should be stopped after the first symptoms of MHA appear - a sharp decrease in hemoglobin values, against the background of which thrombocytopenia appears, as well as an increase in the level of urea, bilirubin, LDH or creatinine in the blood serum;
• lesions of the subcutaneous layers and the skin surface: skin rash of allergic origin, against the background of which erythema, itching, alopecia and hyperhidrosis often occur. Severe forms of skin symptoms are observed sporadically - such as bullous rash, desquamation, ulcers, peeling, blisters, as well as Stevens-Johnson syndrome and TEN;
• respiratory disorders: cough, dyspnea (usually mild, resolves on its own) and runny nose. Bronchospasms (often mild and transient, although sometimes parenteral therapy is required), fibrosing alveolitis, pulmonary edema and hyaline membrane disease in adults are occasionally observed. If a patient experiences such symptoms, therapy should be stopped;
• disorders of the cardiovascular system: peripheral edema. Myocardial infarction, decreased blood pressure, various arrhythmias (often supraventricular) and heart failure are observed occasionally. Clinical symptoms of gangrene and peripheral vasculitis may also occur, as well as capillary leak syndrome;
• reactions from the nervous system: development of insomnia, feelings of drowsiness and headaches, disturbance of blood circulation processes inside the brain, and also ZOE;
• lesions affecting the activity of the musculoskeletal system: myalgia and back pain;
• laboratory test results: increased values of creatinine, GGT, bilirubin, LDH, as well as urea and alkaline phosphatase in the blood serum;
• Systemic disorders: flu-like symptoms were observed most frequently - headaches, fever, myalgia, chills, loss of appetite and asthenia. In addition, hyperhidrosis, a feeling of malaise, runny nose with cough and sleep problems were reported;
• complications, intoxication and damage that occur during the procedure: radiation poisoning (with concomitant radiotherapy), development of “radiation memory”;
• signs of allergy: anaphylactic symptoms occasionally occur.

Moderate skin manifestations may occur at the injection site. Edemas also develop (sometimes peripheral), in some cases on the face; they disappear after the end of therapy.

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Overdose

Gemcitabine has no antidote that can be used in case of overdose.

A clinically acceptable toxicity index is observed when using doses of no more than 5.7 g/ ^m2, which are administered through infusions over half an hour with a frequency of 1 time/2 weeks.

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

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Interactions with other drugs

Specific drug interaction tests have not been performed.

Radiotherapy.

When administered with radiotherapy (or less than a week after), toxicity occurs, which is caused by treatment using different methods. The development of this disorder is determined by the presence of many factors, including the frequency of infusions, the size of the Hematix dose, the scheme according to which radiotherapy is performed, as well as the devices used, the volume and area of irradiation.

Tests have shown that gemcitabine has radiosensitive activity. When it was administered at a dose of 1 g/m2 ^for 1.5 months in combination with therapeutic irradiation of the sternum in patients with non-small cell bronchogenic carcinoma, very severe toxicity was observed in the form of severe pneumonitis, esophagitis, and potentially life-threatening mucositis (especially in those patients who received radiotherapy in significant volumes - with a median therapy volume of 4.795 cm3 ⁾.

In non-small cell bronchogenic carcinoma, it is acceptable to use the drug in smaller doses, taking into account the toxicity provided by radiotherapeutic procedures. Irradiation of the sternum at a dose of 66 Gy was performed together with the use of the drug (dose 0.6 g / m ², 4 infusions), as well as cisplatin (dose 80 mg / m ², 2 infusions) for 1.5 months. The optimally suitable and safe regimen for the use of drugs with medicinal doses of radiation for any type of tumors has not yet been selected.

When not combined with radiotherapy (more than 7 days before or after the procedures), no increase in toxic properties after the use of gemcitabine was detected during the analysis of the information (excluding situations with the development of "radiation memory"). These data demonstrate that the prescription of the drug is permitted after the disappearance of symptoms of acute complications of radiation procedures - at least 1 week after the performance of radiotherapy.

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

Others.

The combination of the drug with attenuated live vaccines (including vaccines against amaryllosis) is prohibited due to the risk of developing a general pathology that can be fatal - this is especially true for people with immunosuppression.

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Storage conditions

Hematix should be kept out of the reach of small children. It is prohibited to freeze the medicine. Temperature values - no more than 25°C.

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Shelf life

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

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Application for children

It is not recommended to prescribe the drug to children, because there is insufficient information about its safety and effectiveness in this category of patients.

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Analogues

Hematix has the following medicinal analogues - Vizgem and Gemzar with Gembitsin, and in addition Gemcitabine-Ebeve, Gemcitabine-Vista with Gembitsin Medak and Gembitsin-Pharmex with Gembitsin-Teva. This also includes Oncogem and Hercizar with Strigem, and in addition Dercin with Cytogem, Gemcitera with Tolgecit and Ongecin with Gemcitabine-Actavis.

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