Etoposide-LENS, 20 mg/ml 10 ml

Pharmacotherapeutic group

Antitocancer agent, alkaloid

ATX code: L01CB01

Pharmacodynamics:

Etoposide is a semi-synthetic derivative of podophyllotoxin. The mechanism of action is associated with inhibition of topoisomerase 11. Etoposide has cytotoxic effect due to DNA damage. The drug blocks mitosis causing cell death in the 02-phase and late S-phase of the mitotic cycle. High concentrations of the drug cause cell lysis in premitotic phase.

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

Pharmacokinetics:

After intravenous administration, the maximum concentration in plasma is 30 µg/ml and is reached after 1-2 hours. The drug is detected in pleural fluid in saliva liver tissue spleen kidney myometrium brain tissue. It penetrates through the blood-brain and placental barriers. Concentrations of etoposide in cerebrospinal fluid vary from undetectable values to 5% of plasma concentrations. The binding to plasma proteins is about 97%.

Atoposide is actively metabolized in the body. Excretion occurs in a biphasic manner. In adults with normal renal and hepatic function, the half-life in the initial phase is on average 06-2 hours and in the terminal phase 53-11 hours. It is excreted by kidneys – 40-60% unchanged and 15% as metabolites within 48-72 hours. 2-16% is excreted with the feces within 72 hours. There are no data on excretion of the drug in breast milk.

Indications

Active ingredient

Composition

1 ml of the concentrate contains:

The active ingredient: etoposide in terms of 100% substance – 20.0 mg.

Auxiliary substances: Benzyl alcohol converted to 100% substance – 30.0 mg; macrogol 300 (polyethylene glycol 300) – 650.0 mg; polysorbate 80 – 80.0 mg; citric acid converted to 100% substance – 5.76 mg; sodium citrate converted to 100% substance – 1.0 mg; ethanol (anhydrous ethanol) – to 1 ml.

How to take, the dosage

When selecting the route of administration of the regimen and doses in each individual case, the data of specialized literature should be followed.

The dosing regimen is established depending on the chemotherapy regimen used (myelosuppressive effects of other drugs in combination as well as the effects of prior radiation therapy and chemotherapy should be considered when choosing a dose). Etoposide-LNS® is administered by intravenous drip for 30-60 minutes in the following doses:

– 50-100 mg/m2 daily for 4-5 days with repeated cycles every 3-4 weeks;

– 100-125 mg/m2 on days 1 3 and 5 with repeated courses after 3 weeks;

In patients with impaired renal function (creatinine clearance 15-50 ml/min) the dose of etoposide should be reduced by 25%. There are no data on the use of etoposide in creatinine clearance < 15 ml/min.

Repeated courses are performed only after normalization of peripheral blood counts.

Before intravenous administration Etoposide-LENS® is diluted in 250 ml of 09% sodium chloride solution or 5% dextrose solution to the final concentration of 02-04 mg/ml. Avoid contact with buffered aqueous solutions with pH higher than 8.

Ahead of use, the solution should be visually evaluated for solids or color changes.

Precautionary Precautions for Use

Tetoposide-LNS® should only be used under the close supervision of a physician experienced in the therapy of cytotoxic drugs.

LENS® must be handled according to the rules for handling cytotoxic drugs In case of contact with skin or mucous membranes, the affected areas must be washed immediately with soap and water.

The suppression of bone marrow function is a dose-limiting toxicity. Regular monitoring of the blood composition should be performed before starting treatment at intervals and before each subsequent course of the drug. If prior to therapy with Etoposide-LENS® there was radiation therapy and/or chemotherapy the dosing regimen should be chosen taking into account the severity of bone marrow function inhibition.

In case of platelet count decreasing below 50000/μl and/or absolute neutrophil count below 500/μl the therapy should be stopped until complete recovery of blood parameters.

In case of anaphylactic reactions Etoposide-LENS® use should be discontinued and treatment with lucocorticosteroids and/or antihistamines should be started with infusion therapy.

– If there are signs of extravasation, the Etoposide-LENS® infusion should be stopped immediately. The remaining drug is administered in another vein. Subcutaneous injections of hydrocortisone are given around

the affected area and 1% hydrocortisone ointment is applied under a dry dressing (until skin hyperemia disappears – usually for 24 hours).

Patients with hepatic or renal insufficiency require adjustment of the dosing regimen and regular monitoring of renal and hepatic function.

Males and women of childbearing age should use reliable contraceptive methods during treatment with Etoposide-LENS®.

Rarely, patients treated with Etoposide-LENS® in combination with other anticancer drugs may develop acute leukemia with or without a preleukemia phase.

The Etoposide-LENS® solution for intravenous administration contains ethanol as an excipient, which may be a risk factor in patients with liver disease, alcoholism, epilepsy and in children.

Interaction

The antitumor effects of etoposide are enhanced when used in combination with cisplatin (note that excretion of etoposide may be impaired in patients previously treated with cisplatin).

Atoposide should not be mixed with other drugs in the same solution. It is not pharmaceutically compatible with solutions having alkaline pH values.

Because of the immunosuppressive effect of the drug and the possibility of severe infection, live vaccines are not recommended during chemotherapy. Vaccination should be done 3 months after completion of therapy.

Special Instructions

Atoposide may impair the ability to operate vehicles and machinery depending on individual sensitivity.

Contraindications

– Hypersensitivity to etoposide or excipients;

– Myelosuppression (neutrophil count below 1500/μL and/or platelet count below 75000/μL);

– Severe liver dysfunction;

Acute infections;

Pregnancy and lactation.

renal impairment alcoholism epilepsy; childhood (safety and effectiveness in children under 2 years of age has not been established).

Side effects

Hematopoietic organs: The decrease in leukocyte and granulocyte counts depends on the dose administered and is the main dose-limiting toxic manifestation of Etoposide-LENS®. The maximum decrease in granulocyte counts is usually seen on days 7-14 after administration of the drug. Thrombocytopenia occurs less frequently and the maximum decrease in platelets is observed on days 9-16 after administration of Etoposide-LENS®. Recovery of blood parameters usually occurs on day 20 after administration of the standard dose. Anemia is rarely observed.

Digestive system disorders: nausea and vomiting occur in approximately 30-40% of patients are moderate and usually do not lead to discontinuation of the drug. Anti-emetics are indicated to control these side effects. In addition, diarrhea abdominal pain stomatitis esophagitis dysphagia anorexia temporary hyperbilirubinemia and increased activity of “liver” transaminases are noted. This occurs most often when doses are used in excess of the recommended doses.

Cardiovascular system disorders: when rapidly administered intravenously, 1-2% of patients experience a temporary decrease in blood pressure which usually recovers when the infusion is stopped and fluids and other supportive therapy are administered. If it is necessary to resume the drug administration, the rate of administration should be reduced.

Allergic reactions: chills fever tachycardia bronchospasm dyspnea and decreased blood pressure. These reactions usually occur during or immediately after etoposide administration and stop when the infusion is stopped and glucocorticosteroids or antihistamines are used.

Skin disorders: reversible alopecia sometimes leading to complete hair loss occurs in 66% of patients. Rarely, pigmentation skin itching recurrence of radiation dermatitis.

Local reactions: phlebitis if the drug gets under the skin – a pronounced local irritation up to necrosis of the surrounding tissues.

Others: rare – peripheral neuropathy somnolence increased fatigue residual taste in the mouth fever interstitial pneumonitis / pulmonary fibrosis malignant exudative erythema (Stevens-Johnson syndrome) toxic epidermal necrolysis (Lyell syndrome) optic neuritis transient vision loss of cortical genesis muscle cramps metabolic acidosis hyperuricemia.

Overdose

Pregnancy use