Etoposide - instructions for use, doses, side effects, contraindications

Etoposide is a semi-synthetic derivative of podophyllotoxin. Etoposide has a cytotoxic effect due to DNA damage. Suppresses topoisomerase I, depresses mitosis, blocks cells in S-02-interphase of the cell cycle, in higher doses is effective: in the phase G2. Does not affect the assembly of microtubules. In high concentrations (10 μg / ml and above) causes lysis of the cells at the stage of entry into mitosis. At low concentrations (0.3-10 μg / ml) inhibits the entry of cells into prophase.Suppresses the penetration of nucleotides through the plasma membrane, which prevents the synthesis and restoration of DNA. Cytotoxic action against normal healthy cells is observed only when high doses are prescribed.

Pharmacokinetics:

After intravenous administration, the maximum plasma concentration is 30 μg / ml and is reached after 1-2 hours.

Bioavailability of etoposide in capsules averages 50%. The drug is found in the pleural fluid, in saliva, liver tissue, spleen, kidneys, myometrium, brain tissue. Penetrates through blood-brain and placental barriers. The concentrations of etoposide in the cerebrospinal fluid range from undetectable values to 5% of the plasma concentration. The connection with plasma proteins is about 97%.

Etoposide is extensively metabolized in the body. Excretion is carried out in a two-phase manner. In adults with normal renal and hepatic function, the half-life in the initial phase is on average 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 excreted with feces 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 part of combined chemotherapy is also used to attract lymphogranulomatosis, non-Hodgkin's, lymphomas, acute monoblast and myeloblastic leukemia, Ewing's sarcoma, trophoblastic tumors, stomach cancer, Kaposi's sarcoma and neuroblastoma.

Contraindications:

Hypersensitivity expressed, myelosuppression (the number of neutrophils below 1500 / μg and / or platelets below 75,000 / μl), severe liver function, acute infections of the viral, fungal and bacterial nature (including herpes, chicken pox), pregnancy, period lactation.

Carefully:Chronic renal failure, alcoholism, epilepsy; children's age (up to 2 years - safety and effectiveness for children not established).

Dosing and Administration:

When choosing the route of administration, treatment and dosage in each individual case, reference should be made to the literature. The dosage regimen is set depending on the chemotherapy regimen used (when choosing a dose, the myelosuppressive effect of other drugs in combination should be considered,as well as the effect of previous radiation therapy and chemotherapy).

Intravenously drip (dissolve in a 0.9% solution of sodium chloride), for 30-60 minutes in the following doses:

1) 50-100 mg / m²/ day from 1 to 5 days, with repetition of cycles every 3-4 weeks;

2) 100 - 125 mg / m²/ day at 1, 3, 5 days; the courses are repeated after 3 weeks.

In chronic renal failure: creatinine clearance more than 50 ml / min - the usual dose, creatinine clearance of 15-50 ml / min - 75% of the prescribed dose. Data on the use of the drug for creatinine clearance less than 15 ml / min are absent (further reduction of dose should be considered).

Repeated courses are performed only after the normalization of peripheral blood. Prior to intravenous administration dilute in 250 ml of 0.9% sodium chloride solution or 5% dextrose solution to a final concentration of 0.2-0.4 mg / ml. Avoid contact with buffered aqueous solutions with a pH above 8. The solution should be visually assessed for solids or discoloration prior to use.

Side effects:

Local reactions: phlebitis with intravenous administration, with the drug falling under the skin - a pronounced local irritant effect, up to the necrosis of surrounding tissues.

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

From the digestive system: nausea, vomiting, occur in about 30-40% of patients, are of moderate nature and do not lead to withdrawal of the drug. Antiemetics are indicated to control these side effects. In addition, there are diarrhea, abdominal pain, stomatitis, esophagitis, dysphagia, decreased appetite, temporary hyperbilirubinemia and increased activity of "hepatic" transaminases, most often when the recommended doses are exceeded.

From the cardiovascular system: with a rapid intravenous infusion in 1-2% of patients, there is a temporary decrease in blood pressure, which usually recovers when the infusion is discontinued, fluid is injected and another maintenance therapy. If it is necessary to resume the administration of the drug, the rate of administration should be reduced.

Allergic reactions: chills, fever, tachycardia, bronchospasm, shortness of breath, lowering blood pressure. They are observed during or immediately after the administration of the drug and cease when the administration and use of glucocorticoids or anti-histamine agents are discontinued.

From the skin: reversible alopecia; sometimes leading to a complete loss of hair (66%). Rarely - pigmentation, itching, radiation dermatitis.

Other: rarely - peripheral neuropathy, drowsiness; increased fatigue, residual taste in the mouth, interstitial pneumonitis / pulmonary fibrosis, malignant exudative erythema (Stevens-Johnson syndrome), toxicepidermal necrolysis (Lyell's syndrome), optic neuritis, transient loss of vision of cortical genesis; muscle cramps, metabolic acidosis, hyperuricemia.

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

Interaction:

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).

Etoposide should not be mixed with other medicines in one solution. Pharmaceutically incompatible with solutions having alkaline pH values.

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:

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

When working with Etoposide, 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 toxicity. 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 radiation therapy and / or chemotherapy was used before the initiation of therapy with etoposide, then the choice of the dosing regimen should be carried out taking into account the severity of the inhibition of bone marrow function.

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.

If anaphylactic reactions occur, the use of Etoposide should be stopped and treatment with glucocorticosteroids and / or antihistamines should be started against the background of infusion therapy.

When there are signs of extravasation, the infusion of etoposide should be stopped immediately. The remaining drug is injected into another vein. Around the affected area, subcutaneous hydrocortisone injections are administered and a 1% hydrocortisone ointment is applied under a dry bandage (until the skin flies out, usually for 24 hours). Patients with hepatic or renal failure need correction of the dosing regimen and regular monitoring of kidney and liver function.

Men and women of childbearing age during treatment with etoposide should use reliable methods of contraception.

Rarely in patients receiving therapy with etoposide in combination with other antitumor drugs, acute leukemia can develop, with or without preleukemia phase.

A solution of etoposide for intravenous administration as an excipient contains ethyl alcohol, which can be a risk factor for patients suffering from liver diseases, alcoholism, epilepsy, and also in children.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, the drug may interfere with the driving of the car, and work with mechanisms, since Etoposide often causes nausea and vomiting.

Form release / dosage:Concentrate for the preparation of a solution for infusions of 20 mg / ml

Packaging:

5 ml in a vial of colorless hydrolytic glass (USP) Type I, sealed with a rubber stopper, crimped with an aluminum cap and a closed plastic cover "Flip Off".

One bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012704 / 01

Date of registration:30.06.2011

The owner of the registration certificate:Okasa Farma Pvt. Ltd.Okasa Farma Pvt. Ltd.

Manufacturer: & nbsp

Okasa Farma Pvt. Ltd. India

Representation: & nbspOkasa Farma Pvt. Ltd.Okasa Farma Pvt. Ltd.

Information update date: & nbsp11.10.2015

Illustrated instructions

Instructions

Etoposide (Etoposide)