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

Antitumor agent. It is a semisynthetic derivative of podophyllotoxin. The mechanism of action is associated with the inhibition of topoisomerase II. Oppresses mitosis, blocks cells in S-G₂-interphase of the cell cycle, in higher doses acts in G₂phase. Cytotoxic action against normal healthy cells is observed only when etoposide is used in high doses.

Pharmacokinetics:

Ingestion etoposide absorbed from the digestive tract. Bioavailability is on average 50%. Distribution in the cerebrospinal fluid is low and variable; the concentration in normal lung tissue is higher than in the presence of metastases in the lungs; a close level of concentrations in the tissues of primary tumors and in normal tissues of the myometrium is determined.

A direct correlation between the etoposide binding rate and the albumin level in the blood plasma of healthy people and patients with cancer has been noted. Metabolised in the liver.

Final half-lifean average of 7 hours. It is excreted by the kidneys - 44-60%, with feces - up to 16%, with bile - 6% or less.

Indications:

Germinogenic tumors (testicular tumors, choriocarcinoma), ovarian cancer, small cell and non-small cell lung cancer, lymphogranulomatosis, non-Hodgkin's lymphomas, stomach cancer (for monotherapy and combined therapy), Ewing's sarcoma, Kaposi's sarcoma, neuroblastoma, breast cancer (with metastases in liver, pleura), acute non-lymphoblastic leukemia, mesothelioma.

ICD-10

II.C73-C75.C74 Malignant neoplasm of adrenal gland

II.C69-C72.C71 Malignant neoplasm of brain

II.C64-C68.C67 Malignant neoplasm of bladder

II.C60-C63.C62 Malignant neoplasm of testis

II.C40-C41.C41 Malignant neoplasm of bones and articular cartilages of other and unspecified sites

II.C30-C39.C34 Malignant neoplasm of bronchi and lungs

II.C15-C26.C16 Malignant neoplasm of stomach

II.C81-C96.C94.7 Other specified leukemia

II.C81-C96.C92.0 Acute myeloid leukemia

XV.O00-O08.O01 Bumpy drift

II.C81-C96.C83 Diffuse non-Hodgkin's lymphoma

II.C81-C96.C81 Hodgkin's disease [lymphogranulomatosis]

II.C45-C49.C46 Kaposi's Sarcoma

Contraindications:

Pronounced myelosuppression (leukopenia less than 1.5-10⁹/ l, thrombocytopenia less than 75-10⁹/ l), acute infections, renal and / or hepatic insufficiency, pregnancy, children under 2 years, hypersensitivity to podophylline or its derivatives.

Carefully:

With caution apply in patients with previous radiation or chemotherapy, with chickenpox, herpes zoster, with infectious lesions of the mucous membranes, with heart rhythm disturbances, with an increased risk of myocardial infarction, liver dysfunction, diseases of the nervous system (epilepsy), chronic alcoholism, in children older than 2 years.

If the renal function is impaired, the dose is reduced in accordance with the values of creatinine clearance.

Use with caution in hypoalbuminemia (possibly increasing the risk of toxic effects of etoposide).

Pregnancy and lactation:

Action category for the fetus by FDA - D.

Contraindicated in pregnancy (possibly mutagenic, teratogenic, carcinogenic effect).

For the duration of treatment, breastfeeding should be discontinued (it is not known whether etoposide in breast milk).

In experimental studies it was established that etoposide has teratogenic and embryotoxic effects.

During treatment and within 3 months after its end, patients of childbearing age need to apply effective methods of contraception.

Dosing and Administration:

Intravenously drip, inside. The dosage regimen is set individually, depending on the indications, the stage of the disease, the condition of the hematopoietic system and the chemotherapy regimen.

Side effects:

From the side hematopoiesis system: leukopenia, anemia; less often - thrombocytopenia.

From the side digestive system: nausea, vomiting; rarely - anorexia, mucositis, diarrhea; when used in high doses - toxic reactions from the liver.

From the side CNS and peripheral nervous system: drowsiness, increased fatigue; defeat of the peripheral nervous system.

From the side metabolism: hyperuricemia; when using high doses - metabolic acidosis.

From the side of cardio-vascular system: tachycardia, arterial hypotension.

From the side reproductive system: azoospermia, amenorrhea.

Allergic reactions: chills, fever, bronchospasm.

Dermatological reactions: alopecia.

Overdose:

Symptoms: increased toxicity (hematologic, from the gastrointestinal tract).

Treatment: symptomatic therapy. The specific antidote is unknown.

Interaction:

With simultaneous use with other drugs that cause myelodepression, additive inhibition of bone marrow function is possible.

When used simultaneously with cisplatin, the clearance of etoposide may decrease and its toxicity may be increased.

Cyclosporine in high doses can reduce the clearance of etoposide and increase the duration of its action, with the possible increase in leukopenia.

Special instructions:

Treatment should be performed by a physician with experience in chemotherapy, and in the presence of conditions necessary to relieve the complications of treatment (sterile box, sufficient arsenal of antibiotics, the possibility of substitution therapy with blood components).

Medical staff are advised to work with the product in gloves (contact with skin may cause a rash). In case of contact with the skin or mucous membranes, the affected areas should be washed immediately with soap and water.

Before and against the background of ongoing therapy should monitor the picture of peripheral blood.

Do not recommend the vaccination of patients and their families.

In experimental studies it was established that etoposide has a mutagenic effect.

Ethanol in the solution of etoposide for intravenous administration may be a risk factor for patients suffering from liver diseases, alcoholism, epilepsy, and also for children.

During treatment should refrain from occupations that require increased attention and rapid psychomotor reactions.

Instructions

Etoposide (Aetoposidum)