Etoposide-Teva, 20 mg/ml 5 ml

Pharmacodynamics

Atoposide is a semi-synthetic derivative of podophyllotoxin used as an antitumor agent. Etoposide has a cytotoxic effect by damaging DNA. The drug blocks mitosis, causing cell death in the G2 phase and the late S phase of the mitotic cycle. High concentrations of the drug cause cell lysis in the premitotic phase.

Atoposide also inhibits nucleotide penetration through the plasma membrane, which prevents DNA synthesis and repair.

Pharmacokinetics

After administration, the drug is found in saliva, liver tissue, spleen, kidney, myometrium, and, to a lesser extent, pleural fluid, bile, and brain tissue.

Atoposide penetrates the placental and, to a small extent, the blood-brain barrier. Values of the concentration of etoposide in cerebrospinal fluid vary from undetectable values to 5% of the concentration in blood plasma. There are no data on excretion of the drug with breast milk. Binding to plasma proteins is about 90%.

Atoposide is actively metabolized in the body. Excretion of etoposide is biphasic. In adults with normal renal and hepatic function the elimination half-life in the initial phase is approximately 1.5 h on average with the elimination half-life in the final phase of 5-11 h. Total clearance in adults ranges from 19-28 ml/min/m2. Renal clearance is 30-40% of the total clearance. Etoposide is excreted with urine as unchanged substance and metabolites (about 40% of the administered dose) within 48 – 72 hours. 2 – 16% is excreted with the feces.

Indications

The main indications for the use of Etoposide are:

Toposide has been reported effective in treating:

Active ingredient

Composition

1 ml (1 vial) contains:

Active ingredients:

Tetoposide 20 mg (100 mg).

Associates:

citric acid anhydrous,

twin-80,

ethanol anhydrous,

propylene glycol 300.

In a bottle of 5 ml.

There is 1 bottle in the carton.

How to take, the dosage

Tetoposide is part of many chemotherapeutic regimens; therefore, the data in the literature should be used to guide the choice of route of administration, regimen and dosage in each individual case.

The doses are 50-100 mg/m2 per day for 5 days, with cycles repeated every 3-4 weeks.

An every other day regimen is also often used, on days 1, 3, and 5. Repeated courses are carried out only after normalization of peripheral blood parameters.

When choosing a dose, the myelosuppressive effect of other drugs in combination, as well as the effect of prior radiation therapy and chemotherapy should be taken into account.

Pre-use, the solution should be visually assessed for solids or color changes.

Pending administration, etoposide is diluted with 0.9% sodium chloride solution or 5% dextrose/glucose solution to a final concentration of 0.2 or 0.4 mg/ml. It should not be allowed to come into contact with buffered aqueous solutions with a pH higher than 8.

Atoposide is administered by a 30-60 minute IV infusion.

Interaction

The antitumor effects of etoposide are enhanced when used in combination with cisplatin; however, it should be considered that excretion of etoposide may be impaired in patients who were previously treated with cisplatin.

Etoposide should not be mixed with other drugs in the same solution.

Special Instructions

Because etoposide is a cytotoxic antitumor drug, proper use and handling precautions must be observed. Infusions should only be administered by medical personnel who have sufficient experience in working with antitumor drugs. Medical personnel are advised to wear gloves. In case of contact with skin or mucous membranes the affected areas should be washed immediately with soap and water.

The suppression of bone marrow function is a dose-limiting effect of etoposide. Regular monitoring of the blood count should be performed before the start of treatment, during intervals and before each subsequent course of etoposide. If radiation therapy and/or chemotherapy have been given prior to therapy with etoposide, an adequate interval between these two therapies should be observed to ensure recovery of bone marrow function. If platelet counts fall below 50,000/mm3 and/or absolute neutrophil counts fall below 500/mm3, therapy should be discontinued until blood counts fully recover.

In case of anaphylactic reactions the administration of etoposide should be stopped and treatment with corticosteroids and/or antihistamines, infusion therapy should be started.

Precautions should be taken when prescribing the drug to patients with hepatic or renal impairment.

As the drug has mutagenic potential, it can cause chromosome damage in human sperm; therefore, men who are treated with etoposide should use contraception.

In rare cases, patients receiving etoposide therapy in combination with other anticancer drugs may develop acute leukemia, with or without a pre-leukemia phase.

Atoposide is intended to be given only as an IV infusion; other routes of administration are not permitted. The drug should be administered with caution to prevent extravasation during the infusion. However, if extravasation does occur, the following measures are taken:

Etoposide contains ethanol as a filler: this may be a risk factor for patients with liver disease, alcoholism, and epilepsy, as well as children.

Contraindications

Side effects

Hematopoietic system disorders: decrease in white blood cell and platelet counts is dose-dependent and is the main dose-limiting toxic manifestation of etoposide. The maximum decrease in granulocyte count is usually observed on days 7-14 after administration of the drug. Thrombocytopenia occurs less frequently, and the maximum decrease in platelets is seen on days 9-16 after administration of etoposide. Recovery of blood parameters usually occurs on day 20 after administration of the standard dose. Anemia is observed infrequently.

Digestive system disorders: nausea and vomiting occur in about one third of patients. Usually these phenomena are moderate, and it is rarely necessary to cancel the treatment because of them. To control these side effects, antiemetics are indicated. Diarrhea, abdominal pain, stomatitis, esophagitis, dysphagia, and anorexia have also been reported. Mild temporary hyperbilirubinemia and elevated serum transaminase levels occasionally occur. This occurs more often with the use of doses in excess of the recommended doses.

Cardiovascular system disorders: when rapidly injected intravenously, 1-2% of patients experience a temporary decrease in BP, which usually recovers when the infusion is stopped and fluids or other supportive therapy are administered. If resumption of etoposide is necessary, the rate of administration should be reduced.

Allergic reactions: anaphylactic-like symptoms such as chills, fever, tachycardia, bronchospasm, dyspnea, apnea. These reactions are usually observed during or immediately after etoposide administration and cease when the infusion is stopped. However, fatal cases associated with bronchospasm have also been reported. If such reactions occurred, therapy was discontinued and vasopressor drugs, corticosteroids, antihistamines and infusion and transfusion therapy were administered if necessary.

Skin and skin appendages: reversible alopecia, sometimes leading to complete hair loss, occurs in about 66% of patients. The occurrence of pigmentation, itching, urticaria has also been noted. In one case there has been a recurrence of radiation dermatitis.

Other toxic manifestations: peripheral neuropathy, somnolence, increased fatigue, residual taste in the mouth, fever, transient cortical blindness are occasionally observed.

Overdose

To date, no cases of overdose have been reported with etoposide in humans. It can be assumed that the main manifestation of overdose would be toxic effects on the blood and gastrointestinal tract. In such cases, mainly symptomatic therapy is indicated. There are no specific antidotes.

Pregnancy use

The drug is contraindicated during pregnancy and lactation.