Vepezid

Vepesid is an antitumor drug that contains the element etoposide (a semi-artificial derivative of podophyllotoxin).

Indications Vepeside

It is used to treat people with oncological diseases, including:

• small cell lung carcinoma;
• the last stages of lymphoma, as well as malignant lymphogranulomatosis;
• neoplasms in the area of the testicles or ovaries that are germ cell in nature;
• exacerbation of relapse of leukemia of a non-lymphocytic nature;
• chorionic carcinoma;
• non-small cell pulmonary neoplasms and other solid tumors;
• angioendothelioma of the skin and bone sarcoma;
• gastric cancer;
• neoplasms that have a trophoblastic form;
• neuroblastoma.

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Release form

The product is produced in the form of a concentrate for infusion fluid, in 5 ml vials. The box contains 1 such vial.

The medicine is also sold in capsules, 20 pieces per bottle, 1 bottle per pack.

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Pharmacodynamics

Data obtained from experimental tests showed that Vepesid helps interrupt the cell cycle at the G2 stage. The drug in vitro slows down the incorporation of thymidine into DNA, in large portions (above 10 μg/ml) it helps cell lysis at the mitosis stage, and in small portions (within 0.3-10 μg/ml) it suppresses cell activity at the initial stage of prophase.

Vepesid is effective against many human neoplasms. The severity of etoposide's effect in many patients depends on how often the drug is used (in tests, the best result was demonstrated during a course of use over a period of 3-5 days).

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Pharmacokinetics

During the tests, no significant differences were found in the metabolic processes and elimination pathways of etoposide after intravenous or oral administration. In adults, there is a direct correlation between the level of drug clearance and the CC indices, and in addition, with plasma albumin values.

The Cmax and AUC values of etoposide after administration of doses falling within the therapeutic range show a similar tendency to decrease after both intravenous and oral administration.

The average bioavailability values of capsules are approximately 50% (variability is 26-76%). With an increase in the portion, the level of bioavailability decreases (during tests, the bioavailability values were 55-98% after taking 0.1 g of the drug, and 30-66% after taking 0.4 g).

Distribution processes and excretion of the substance etoposide have a two-stage structure. The half-life of the 1st stage of distribution requires 90 minutes, and the half-life of the 2nd (terminal) stage requires 4-11 hours. The indicators of the active element in the blood serum are linear and depend on the dosage size. After daily (within 4-6 days) use of 0.1 g / m ² LS etoposide does not accumulate in the body.

Vepesid hardly passes through the BBB. The excretion of the substance occurs mainly through the kidneys (approximately 42-67% of the dosage); a small part of it (maximum 16%) is excreted through the intestine. About 50% of the drug is excreted unchanged.

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Dosing and administration

Mode of use of infusion concentrate.

The concentrate must be used to prepare an infusion solution. The dosage of the drug is selected for each person individually. The mode of application, the therapeutic course, as well as concomitant treatment procedures can only be selected by a doctor with experience in the treatment of oncological diseases. When selecting drugs for complex therapy, it is necessary to take into account the myelosuppressive effect of all drugs, as well as the effect of previously conducted radiation or chemotherapy on the bone marrow.

The introduction of liquid should occur at a low rate (within 0.5-1 hour). On average, the medicinal dose is 0.05-0.1 g/ ^m2 per day, over a period of 4-5 days. Such 4-5-day treatment courses should be repeated at intervals of 3-4 weeks.

An alternative method is the introduction of an infusion of 100-125 mg/ ^m2 per day, with a frequency of “every other day” (the procedure should be performed on the 1st, 3rd, and 5th days of the course).

Treatment cycles can be repeated only after the peripheral blood values have returned to normal.

To prepare the infusion fluid, the required portion of the concentrate is diluted in saline NaCL or 5% glucose infusion solution. The final drug levels in the infusion fluid should be 0.2-0.4 mg/ml.

Scheme of application of medicinal capsules.

The medicine is taken orally. The dosage portion size is selected by a doctor with experience in treating oncological pathologies. When selecting a treatment course, it is necessary to take into account the myelosuppressive effect of other drugs included in the treatment regimen, as well as the effect on the bone marrow of previously conducted chemotherapy or radiation therapy sessions.

Capsules are often taken in a daily dose of 50 mg/ ^m2 for a period of 3 weeks. Such cycles are repeated every 28 days. Alternatively, a regimen of 0.1-0.2 g/m2 ^{of the} drug orally per day for 5 consecutive days can be used. Such 5-day courses are often repeated at intervals of 21 days.

Repeated therapeutic courses are allowed only after stabilization of the values of formed blood indices. Before the beginning of new treatment cycles, and also during the entire course of treatment, monitoring of peripheral blood indices is performed.

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Use Vepeside during pregnancy

Vepesid is not prescribed to pregnant women. If a woman becomes pregnant, she should be warned about the possible development of complications and the toxic properties of the drug.

The drug has a toxic effect on reproductive activity. Both women and men using etoposide for treatment are required to use reliable contraceptives during this period - taking into account the possible negative effect of the drug on spermatogenesis, as well as the teratogenic and embryotoxic effect of cytostatics.

During lactation, the drug may be used only if breastfeeding is discontinued.

Contraindications

Main contraindications:

• It is prohibited to prescribe the medication in the presence of hypersensitivity to etoposide or additional elements;
• The concentrate and capsules are not used in therapy for people with myelosuppression (this includes people with neutrophil counts below 500/mm3 ^, as well as platelets below 50,000/mm3 ⁾;
• should not be prescribed to people with severe infections in the acute stage.

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Side effects Vepeside

The use of drugs in monotherapy quite often causes leukopenia in patients. In this case, the minimum values were often noted by the 7th-14th day of treatment. The development of thrombocytopenia was recorded less often, with the appearance of minimum values by the 9th-16th day of treatment. By the end of the 3rd week of the treatment cycle, blood values in most people stabilized.

The administration of the drug may lead to the development of toxicity in the gastrointestinal tract, and sometimes cause nausea with vomiting. If the patient experiences vomiting, he/she should be given antiemetics. Toxicity in the gastrointestinal tract was expressed less strongly when administering Vepesid infusions. Stool disorders, loss of appetite and the appearance of stomatitis were recorded sporadically.

The use of infusions may cause a decrease in blood pressure in humans, as well as histamine signs, but without symptoms of cardiotoxicity. If a histamine effect and a decrease in blood pressure are observed, the administration of the drug should be stopped immediately. To prevent a decrease in blood pressure, the drug should be administered at a low speed through a dropper (with jet injections, the risk of negative symptoms increases).

When treated with etoposide, patients may experience allergic symptoms, including bronchospasm, hyperthermia, dyspnea, and tachycardia. If the patient develops intolerance, it is necessary to prescribe antihistamines, adrenergic, or corticosteroid medications (a more specific regimen depends on the doctor's indications).

The use of Vepesid may cause the development of alopecia, polyneuropathy (the occurrence of such a disorder is more likely if the drug is combined with medications containing periwinkle alkaloid), photosensitivity, a feeling of drowsiness or fatigue, and in addition, an increase in the activity of liver transaminases.

Nephrotoxic or hepatotoxic effects are not characteristic of the substance etoposide, but during the entire period of treatment, regular examination of the liver and kidney function is required.

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Overdose

^{If 2.4-3.5 g/ m3} of the drug is administered daily for 3 days, it will cause severe intoxication of bone marrow tissues, as well as the development of inflammation in the mucous membranes. Also, the use of high doses of drugs can cause the development of a metabolic form of acidosis and hepatotoxic symptoms.

People with etoposide poisoning should be immediately prescribed detoxification and symptomatic measures. In case of overdose, it is necessary to monitor the functioning of vital systems and control peripheral blood indices. After intoxication, the decision on continuing the use of etoposide is made by the attending physician.

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Interactions with other drugs

When Vepesid is combined with cisplatin, an increase in the antitumor effect of the first drug is observed. It is necessary to take into account that in people who have previously used cisplatin, there is a disorder in the excretion of etoposide, and the likelihood of developing adverse reactions increases.

The drug has immunosuppressive properties, which is why severe infections may occur when using live vaccines. Vaccination procedures that use live agents are strictly prohibited during treatment with Vepesid (immunization with live substances is allowed at least 3 months after the last dose of etoposide).

The myelosuppressive effect of the drug is potentiated when combined with other cytostatics or medications that potentially contribute to the development of myelosuppression.

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Storage conditions

Vepesid is kept in a place closed to small children and protected from sunlight. The medication should be stored under standard temperature conditions for therapeutic agents.

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Shelf life

Vepesid is allowed to be used within 36 months from the date of release of the drug.

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Application for children

The drug is prohibited for use in pediatrics.

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Analogues

Analogues of the drug are Lastet and Fitozid with Etoposide.

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