Etoposide-Teva - instructions for use, dose, side effects, contraindications

Etoposide is a semi-synthetic derivative of podophyllotoxin. The mechanism of action is associated with the inhibition of topoisomerase II. Etoposide has a cytotoxic effect due to DNA damage. The drug blocks mitosis, causing cell death in the Ophase and late Sphase of the mitotic cycle. High concentrations of the drug cause lysis of cells in the pre-pertussis phase. Etoposide also suppresses the penetration of nucleotides through the plasma membrane, which prevents the synthesis and restoration of DNA.

Pharmacokinetics:

After intravenous administration, the maximum concentration in the blood plasma (Cmax) is 30 μg / ml and is achieved after 1-2 hours. The drug is found in pleural fluid, saliva, liver tissue, spleen, kidneys, brain tissue. The concentration of etoposide in the cerebrospinal fluid varies from undetectable values to 5% of the concentration in the blood plasma. Etoposide penetrates through blood-brain and placental barriers. The connection with plasma proteins is about 97%. The total clearance of the drug is 16-36 ml / min / m².

Etoposide is actively metabolized in the body. Isolation is carried out in a two-phase way. In adults with normal renal and hepatic function, the elimination half-life (T1 / 2) in the initial phase an average of 0.6-2 hours and in the terminal phase - 5.3-11 hours. It is excreted by the kidneys - 40-60% unchanged and 15% in the form of metabolites for 48-72 hours. 2-16% is secreted by the intestine within 72 hours. Data on the isolation of the drug with breast milk are absent.

Indications:

The main indications for use are germinogenic tumors of testis and ovaries, small cell lung cancer.

Etoposide as a part of combined chemotherapy is also used in the treatment of lymphogranulomatosis, non-Hodgkin's lymphomas, acute monoblast and myeloblastic leukemia, Ewing's sarcoma, trophoblastic tumors, stomach cancer, Kaposi's sarcoma and neuroblastoma.

Contraindications:

- Hypersensitivity to etoposide or excipients included in the preparation;

- Severe myelosuppression (neutrophil count below 1500 / μL and / or platelets below 75,000 / μL);

- Pronounced violations of the liver;

- Acute infections;

- Pregnancy and lactation

Carefully:kidney failure, alcoholism, epilepsy, children's age (lack of sufficient clinical data on safety and efficacy).

Dosing and Administration:

Etoposide is a part of many chemotherapy regimens, therefore, when selecting the route of administration, regimen and dosage in each individual case, reference should be made to the literature.

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

Doses are 50-100 mg / m² a day for 5 days, with a repetition of cycles every 3-4 weeks. Also, the mode of administration every other day is 50-150 mg / m² in the 1st, 3rd and 5th days, the courses should be repeated no more often than after 21 days.

In patients with impaired renal function (creatinine clearance 15-50 ml / min), the dose of etoposide should be reduced by 25%. At clearance of creatinine <15 ml / min there is no data on the use of etoposide. Repeated courses are held only after the normalization of peripheral blood.

When choosing a dose, you should consider the myelosuppressive effect of other drugs in combination, as well as the effect of previous radiation therapy and chemotherapy.

Before use, a visual assessment of the solution should be carried out to identify particulate matter or discoloration.

Before the introduction etoposide diluted with 0.9% sodium chloride solution or 5% dextrose solution to a final concentration of 0.2 or 0.4 mg / ml. The solutions obtained remain stable for 24 and 120 hours, respectively.

Do not allow contact with buffer aqueous solutions with pH> 8.

Side effects:

From the hematopoiesis: Myelosuppression depends on the dose administered and is the main dose-limiting toxic effect of etoposide.The maximum decrease in the number of granulocytes is usually observed on the 7-14 day after the administration of the drug. Thrombocytopenia occurs less often, and the maximum decrease in the number of platelets is observed on the 9-16th day after the administration of etoposide. Recovery of blood values occurs usually on day 20 after the administration of a standard dose. Anemia is rare.

From the digestive system: nausea and vomiting occurs in approximately 30-40% of patients, are mild and usually do not lead to withdrawal of the drug. To control these side effects, antiemetic drugs are indicated. In addition, there are diarrhea, abdominal pain, stomatitis, esophagitis, dysphagia, anorexia. When high doses of etoposide are used, temporary hyperbilirubinemia, increased activity of "liver" transaminases and alkaline phosphatase can be observed.

From the cardiovascular system: with a rapid intravenous injection in 1-2% of patients, there is a temporary decrease in blood pressure, which is usually restored by stopping infusion and injecting fluids or other maintenance therapy. If it is necessary to resume the administration of etoposide, the rate of administration should be reduced.There were rare cases of arrhythmia and myocardial infarction.

From the immune system: symptoms reminiscent of anaphylactic, such as chills, fever, tachycardia, bronchospasm, shortness of breath and lowering of blood pressure. These reactions are usually observed during or immediately after the administration of etoposide and cease upon discontinuation of infusion and the use of glucocorticosteroids or antihistamines. There were reported cases of apnea with resumption of breathing after withdrawal of the drug and sudden deaths in bronchospasm. There was also an increase in blood pressure and a "tide" of blood. Arterial pressure usually normalizes within a few hours after the infusion has stopped.

From the skin and skin appendages: reversible alopecia, sometimes leading to complete loss of hair, occurs in approximately 66% of patients. Rarely - pigmentation, itching, rash, hives, recurrence of radiation dermatitis.

Local Reakies: phlebitis, when the product gets under the skin - a pronounced local irritant effect up to the necrosis of surrounding tissues.

Other: rarely - peripheral neuropathy, drowsiness, increased fatigue,residual taste in the mouth, fever, interstitial pneumonitis / pulmonary fibrosis, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), optic neuritis, transient loss of cortical origin, muscle cramps, metabolic acidosis, hyperuricemia, very rarely - a tumor disintegration syndrome (sometimes leading to death).

Overdose:The main alleged overdose is myelosuppression and toxic effects from the gastrointestinal tract. Treatment is symptomatic. The specific antidote is not known.

Interaction:

Etoposide should not be mixed with other medicines in one solution. Pharmaceutically incompatible with solutions having alkaline pH values. The antitumor effect of etoposide is enhanced when used in combination with cisplatin, (note that in patients previously treated with cisplatin, etoposide removal may be impaired).

In connection with the immunosuppressive effect of the drug and the possibility of developing a serious infection, it is not recommended to use live vaccines during chemotherapy.Vaccination should be carried out 3 months after the completion of therapy.

Special instructions:

The drug Etoposide-Teva should be used only under the constant supervision of a doctor who has experience of therapy with cytotoxic drugs.

When working with the drug Etoposide-Teva, you should follow the rules for handling cytotoxic drugs. In case of contact with skin or mucous membrane, the affected areas should be washed immediately with soap and water.

Suppression of bone marrow function is a dose-limiting action of the drug Etoposide-Teva. Regular monitoring of the blood composition should be performed before the beginning of treatment, in breaks and before each subsequent course of the drug. If prior to the initiation of therapy with Etoposide-Teva, radiation therapy and / or chemotherapy was performed, then the choice of dosage regimen should be made taking into account the severity of bone marrow depression.

In case of a decrease in the number of platelets below 50,000 / μL and / or the absolute number of neutrophils to 500 / μl, therapy should be discontinued until the blood counts are fully restored.

When anaphylactic reactions occur, the use of Etoposide-Teva should be stopped and treatment initiatedglucocorticosteroids and / or antihistamines.

When there are signs of extravasation, the drug Etoposide-Teva should be discontinued immediately. The remaining drug is injected into another vein. Carried around the affected site subcutaneous injections of hydrocortisone and for the dry dressing is applied 1% hydrocortisone ointment (until until no flushing of the skin - typically for 24 h). Patients with hepatic or renal failure need correction of the dosing regimen and regular monitoring of kidney and liver function.

Occasionally patients receiving therapy with etoposide-Teva in combination with other antineoplastic agents may develop acute leukemia as predleykoznoy phase with and without it.

Men and women of childbearing age during treatment with Etoposide-Teva should use reliable methods of contraception.

A solution of etoposide-Teva preparation for intravenous administration as filler comprises ethyl alcohol, which may be a risk factor for patients with liver disease, alcoholism, epilepsy, and also for children.

Form release / dosage:Concentrate for the preparation of a solution for infusions of 100 mg / 5 ml, 200 mg / 10 ml, 400 mg / 20 ml, 500 mg / 25 ml, 1000 mg / 50 ml (20 mg / ml).

Packaging:

Concentrate for the preparation of a solution for infusions of 100 mg / 5 ml, 200 mg / 10 ml, 400 mg / 20 ml, 500 mg / 25 ml, 1000 mg / 50 ml (20 mg / ml) in vials of colorless glass with a stopper of chlorobutyl rubber , an aluminum cap equipped with a protective cap - an insert of colored polypropylene. The vials are covered with a transparent polyethylene film.

1 bottle with instructions for use in a cardboard box.

Storage conditions:

List B.

In the dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012285 / 01

Date of registration:03.11.2009

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

PHARMACHEMIE, B.V. Netherlands

Representation: & nbspTeva Teva Israel

Information update date: & nbsp11.10.2015

Illustrated instructions

Instructions

Etoposide-Teva (Etoposide-teva)