Vapezid

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

Indications Viperidae

It is used to treat people with cancer, among them:

• pulmonary carcinoma of small cell type;
• the last stages of lymphoma, as well as malignant-type lymphogranulomatosis;
• neoplasms in the field of testicles or ovaries, having germinogenic nature;
• exacerbation of relapse of leukemia, which has a non-lymphocytic character;
• chorion carcinoma;
• non-small cell lung neoplasms and other solid tumors;
• angioendothelioma of the skin and bone sarcoma ;
• gastric cancer;
• neoplasms with trophoblastic form;
• a non-fibroblast.

[1], [2], [3]

Release form

The release is made in the form of a concentrate for infusion fluid, in flacons with a capacity of 5 ml. Inside the box there is one such bottle.

The medicine is also sold in capsules, in the amount of 20 pieces inside the bottle, 1 bottle in a pack.

[4], [5], [6]

Pharmacodynamics

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

Vepesid is effective in many new formations in humans. The severity of the effects of etoposide in many patients depends on how often the drug is used (in tests, the best result was demonstrated during the course of use during 3-5 days).

[7]

Pharmacokinetics

During the tests, there were no significant differences in metabolic processes and routes of etoposide removal after intravenous or oral administration. In an adult, there is a direct correlation of the level of drug clearance with QA indices, and in addition to plasma values of albumin.

The Cmax and AUC of etoposide after administration of dosages falling within the therapeutic range have a similar tendency to decrease both after intravenous administration and when ingested.

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

Distribution processes and excretion of the substance etoposide have a two-stage structure. Half-way through the first stage of distribution takes 90 minutes, and the passage of the second (terminal) - 4-11 hours. The indices of the active element inside the blood serum are linear and depend on the size of the dosage. After everyday (within 4-6 days) application of 0.1 g / m ² LS etoposide does not accumulate inside the body.

Vepesid almost does not pass through the BBB. Excretion of the substance mainly occurs 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.

[8], [9], [10], [11]

Dosing and administration

Mode of use of infusion concentrate.

Concentrate should be used in the manufacture of infusion solution. Dosages of the drug are selected for each person separately. The mode of application, therapeutic course, and also accompanying medical procedures can be selected only by a doctor with experience in the treatment of oncological diseases. During the selection of drugs for complex therapy, it is necessary to take into account the myelosuppressive effect of all medications, and in addition the effect of previous radiation or chemotherapy on the bone marrow.

The introduction of fluid should occur at a low speed (during the 0.5-1 hour). On average, the drug dose is 0.05-0.1 g / m ² per day, in the 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 / m ² per day, with the frequency "in a day" (the procedure should be performed on the 1st, 3rd, and 5th days of the course).

Repeat the treatment cycles can only be after the normalization of the values of peripheral blood.

To make the infusion liquid, the required portion of the concentrate is diluted in NaCl saline or 5% glucose for infusion. The final indices of the drug inside the infusion fluid should be equal to 0.2-0.4 mg / ml.

Scheme of application of medicinal capsules.

The medicine is consumed inside. The size of the dose is chosen by a doctor who has experience in the treatment of oncological pathologies. When selecting a treatment course, one must always take into account the myelosuppressive effect of other drugs that are included in the treatment regimen, and in addition the effect on the bone marrow of previous chemotherapy or radiotherapy sessions.

Capsules are often taken in a daily dose of 50 mg / m ², during a period of 3 weeks. Such cycles are repeated every 28 days. As an alternative, it is possible to use a regimen with 0.1-0.2 g / m ² LS per day applied per day , for 5 consecutive days. Similar 5-day courses are often repeated at intervals of 21 days.

Performing therapeutic courses is allowed again only after the values of the formed blood values have stabilized. Before the start of new treatment cycles, and in addition, during the entire course of treatment, the values of peripheral blood are monitored.

[19], [20], [21]

Use Viperidae during pregnancy

Vapezid is not prescribed for 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 who use etoposide for treatment need to use reliable contraceptives during this period, taking into account the possible negative effect of drugs on spermatogenesis, as well as the teratogenic and embryotoxic effect of cytostatics.

With lactation, the drug is only allowed if breastfeeding is refused.

Contraindications

The main contraindications:

• It is forbidden to prescribe a medicament if there is hypersensitivity to etoposide or additional elements;
• concentrate and capsules are not used in therapy in people with myelosuppression (this includes people with neutrophil counts below 500 / mm ³, and platelets below 50,000 / mm ³ );
• It can not be prescribed to people with serious infections at the stage of exacerbation.

[12], [13], [14]

Side effects Viperidae

The use of drugs with monotherapy often causes patients to develop leukopenia. At the same time, often the minimum indicators were noted by the 7-14th day of treatment. The development of thrombocytopenia was recorded less frequently, with the appearance of minimal indicators by the 9th-16th day of treatment. By the end of the third week of the treatment cycle, blood levels in most people have stabilized.

The introduction of drugs can lead to the development of toxicity in the gastrointestinal tract, and sometimes cause nausea with vomiting. If a patient is vomiting, give him antiemetics. The toxicity inside the gastrointestinal tract was less pronounced with the introduction of Vepesid infusions. Disorders of stool, loss of appetite and the appearance of stomatitis were registered separately.

The use of infusions can cause people to lower blood pressure, as well as histamine signs, but without the symptoms of cardiotoxicity. If there is a histamine effect and a decrease in blood pressure, you must immediately stop the injection of the drug. To prevent a decrease in blood pressure, it is necessary to administer the drug at a low speed through a dropper (with jet injections, the risk of negative symptoms increases).

When treating with etoposide, patients may experience allergic symptoms, including bronchospasm, hyperthermia, dyspnoea and tachycardia. If the patient develops intolerance, it is required to prescribe to him the use of antihistamine, adrenergic or corticosteroid medications (a more specific scheme depends on the medical indications).

The use of Vepisid can lead to the development of alopecia, polyneuropathy (the appearance of such a disorder is more likely if the medicine is combined with medicines containing a periwinkle alkaloid), photosensitivity, a feeling of drowsiness or fatigue, and in addition an increase in the activity of the transaminase activity of the liver.

Nephrotoxic or hepatotoxic effects are not characteristic for the substance etoposide, but during the entire period of treatment it is required to be regularly monitored for liver function with the kidneys.

[15], [16], [17], [18]

Overdose

If you inject 2,4-3,5 g / m ^{3 of} medication every day for 3 days , it will cause strong 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 metabolic form of acidosis and hepatotoxic symptoms.

People with poisoning with etoposide should immediately be prescribed detoxification and symptomatic activities. When an overdose is necessary to monitor the operation of vital systems and monitor the performance of peripheral blood. After intoxication, the decision on the continuation of the use of etoposide is taken by the attending physician.

[22], [23]

Interactions with other drugs

When combining Vepesid with cisplatin, the antitumor effect of the first drug is increased. It is necessary to take into account that in people who used cisplatin before, there is an upset of the excretion of etoposide, and the likelihood of developing negative reactions increases.

The medication has immunosuppressive properties, which can lead to infections with a high degree of severity when using live vaccines. Vaccination procedures in which live remedies are used are categorically prohibited during treatment with Vepesid (immunization with living 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 promote the development of myelosuppression.

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

Storage conditions

Vapezide is kept in a place closed to small children, where sunlight does not penetrate. The medicament should be stored in standard temperature conditions for therapeutic agents.

[28], [29]

Shelf life

Vapezide is allowed to be used within 36 months of the release of the drug.

[30]

Application for children

It is forbidden to use the medicine in pediatrics.

[31], [32], [33], [34]

Analogues

Analogues of the drug are the drugs Lusteth and Phytoside with Etoposide.

[35], [36], [37], [38], [39], [40]