Etoposide-Teva concentrate for infusion solution 20mg/ml vial, 5ml

Composition

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1 ml (1 bottle) contains:

Active ingredients:

etoposide 20 mg (100 mg).

Auxiliary substances:

citric acid anhydrous,

tween-80,

ethanol anhydrous,

propylene glycol 300.

In a 5 ml bottle.

In a cardboard box 1 bottle.

Pharmacological action

Pharmacodynamics

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

Etoposide also inhibits the penetration of nucleotides across the plasma membrane, which interferes with DNA synthesis and repair.

Pharmacokinetics

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

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

Etoposide is actively metabolized in the body. Etoposide is isolated in a two-phase manner. In adults with normal renal and hepatic function, the initial half-life averages approximately 1.5 hours with a final half-life of 5-11 hours. Total clearance in adults ranges from 19-28 ml / min / m2. Renal clearance is 30-40% of the total clearance. Etoposide is excreted in the urine as an unchanged substance and metabolites (about 40% of the administered dose) within 48-72 hours. 2-16% is excreted in the faeces.

Indications

The main indications for the use of Etoposide are:

• germ cell tumors of the testis and ovaries;
• small cell lung cancer;

Etoposide has been reported to be effective in the treatment of:

• cancer of the bladder;
• lymphogranulomatosis;
• non-Hodgkin’s lymphoma;
• acute monoblastic and myeloblastic leukemia;
• Ewing’s sarcoma;
• trophoblastic tumors;
• stomach cancer;
• Kaposi’s sarcoma;
• neuroblastoma.

Use during pregnancy and lactation

It is contraindicated to use the drug during pregnancy and lactation.

Contraindications

• Hypersensitivity to the drug;
• severe myelosuppression;
• severe liver function disorders;
• acute infections;
• pregnancy and lactation.
• use in children: safety and efficacy have not been established.

Side effects

From the hematopoietic system: a decrease in the number of white blood cells and platelets depends on the dose and is the main dose-limiting toxic manifestation of etoposide. The maximum decrease in the number of granulocytes is usually observed on 7-14 days after use of the drug. Thrombocytopenia occurs less frequently, and the maximum decrease in platelets is observed on days 9-16 after etoposide use. Recovery of blood counts usually occurs on the 20th day after the standard dose is administered. Anemia is infrequent.

From the digestive system: nausea and vomiting occur in about one-third of patients. Usually, these phenomena are moderate in nature, and it is rare to resort to discontinuing treatment because of them. Antiemetics are indicated to control these side effects. In addition, diarrhea, abdominal pain, stomatitis, esophagitis, dysphagia, and anorexia were noted. Sometimes there is a slight temporary hyperbilirubinemia and an increase in the level of transaminases in the blood serum. Most often, this occurs when using doses that exceed the recommended ones.

From the cardiovascular system: with rapid intravenous use,1-2% of patients have a temporary decrease in blood pressure, which is usually restored when the infusion is stopped and fluids or other maintenance therapy is administered. If it is necessary to resume etoposide use, the rate of use should be reduced.

Allergic reactions: symptoms that resemble anaphylactic ones, such as chills, fever, tachycardia, bronchospasm, shortness of breath, apnea. These reactions usually occur during or immediately after etoposide use and stop when the infusion is stopped. However, deaths related to bronchospasm have also been reported. If such reactions occurred, therapy was discontinued and, if necessary, vasopressors, corticosteroids, antihistamines, and infusion-transfusion therapy were administered.

From the skin and skin appendages: reversible alopecia, sometimes leading to complete hair loss, occurs in approximately 66% of patients. There is also the appearance of pigmentation, itching, urticaria. In one case, a recurrence of radiation dermatitis was observed.

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

Interaction

The antitumor effect of etoposide is enhanced when used in combination with cisplatin, but it should be borne in mind that in patients who have previously received cisplatin treatment, etoposide excretion may be impaired.

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

How to take, course of use and dosage

Etoposide is included in many chemotherapeutic treatment regimens, and therefore, when choosing the route of use, regimen and doses in each individual case, you should be guided by the data of the specialized literature.

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

The use regimen is also often used every other day – on the 1st,3rd and 5th days. Repeated courses are carried out only after normalization of peripheral blood parameters.

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

Before use, the solution should be visually evaluated for solid particles or discoloration.

Before use, 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. Do not allow contact with buffer aqueous solutions with a pH higher than 8.

Etoposide is administered by a 30-60-minute intravenous infusion.

Overdose

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

Special instructions

Since etoposide is a cytotoxic antitumor drug, it is necessary to observe measures for its proper use and handling. Infusions can only be performed by medical professionals who have sufficient experience with antitumor drugs. Medical personnel are advised to wear gloves. In case of contact with the skin or mucous membrane, the affected areas should be washed immediately with soap and water.

Suppression of bone marrow function is a dose-limiting effect of etoposide. Regular monitoring of blood composition should be performed before starting treatment, during breaks, and before each subsequent course of etoposide. If radiation therapy and/or chemotherapy have been performed prior to etoposide therapy, then a sufficient interval should be observed between these two types of therapy to ensure restoration of bone marrow function. If the platelet count drops below 50,000/mm3 and/or the absolute neutrophil count drops to 500/mm3, therapy should be discontinued until the blood counts are fully restored.

If anaphylactic reactions occur, etoposide should be discontinued and treatment with corticosteroids and/or antihistamines, as well as infusion therapy, should be initiated.

Caution should be exercised when prescribing the drug to patients with hepatic or renal insufficiency.

Since this drug has mutagenic potential, it can cause damage to human sperm chromosomes; therefore, men receiving etoposide therapy should use contraception.

Occasionally, patients receiving etoposide therapy in combination with other antitumor drugs may develop acute leukemia, both with and without a pre-leukemic phase.

Etoposide is intended only for use in the form of intravenous infusion, other routes of use are not allowed. use of the drug should be carried out with caution to avoid extravasation during the infusion. However, if extravasation still occurs, the following measures are taken: :

• perfusion should be stopped as soon as a burning sensation appears;
• subcutaneous injections of corticosteroid (hydrocortisone) should be made around
• the affected area;1% hydrocortisone ointment should be applied to the affected area until erythema disappears;
• a dry bandage should be applied to the affected area for 24 hours.

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

Form of production

Concentrate for preparation of solution for infusions

Storage conditions

In a dark place, at a temperature of 15-25 °C

Shelf life

3 years

Active ingredient

Etoposide

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as directed by your doctor

Indications

Cancer