Etoposide-LNS concentrate for infusion solution 20mg/ml vial, 10ml

Composition

1 ml of concentrate contains:

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

Auxiliary substances: benzyl alcohol in terms of 100% substance was 30.0 mg; macrogol 300 (polyethylene glycol 300) – 650,0 mg; Polysorbate 80 – 80,0 mg; citric acid in terms of 100% substance – 5.76 mg; sodium citrate in terms of 100% substance – 1.0 mg; ethanol (anhydrous ethanol) up to 1 ml.

Pharmacological properties

Pharmacotherapeutic group,

an antitumor agent, an alkaloid

ATX Code: L01CB01

Pharmacodynamics :

Etoposide is a semi-synthetic derivative of podophyllotoxin. The mechanism of action is related to the inhibition of topoisomerase 11. Etoposide has a cytotoxic effect due to DNA damage. The drug blocks mitosis by causing cell death in the 02-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 through the plasma membrane, which prevents DNA synthesis and repair.

Pharmacokinetics:

After intravenous use, the maximum plasma concentration is 30 mcg / ml and is reached in 1-2 hours. The drug is found in the pleural fluid in saliva liver tissue spleen kidneys myometrium and brain tissues. Penetrates through the blood-brain and placental barriers. Concentrations of etoposide in the cerebrospinal fluid vary from undetectable values to 5% of the concentration in blood plasma. Binding to plasma proteins is about 97%.

Etoposide is actively metabolized in the body. Removal is carried out in a two-phase method. In adults with normal renal and hepatic function, the average elimination half-life is 06-2 hours in the initial phase and 53-11 hours in the terminal phase. It is excreted by the kidneys-40-60% in unchanged form and 15% in the form of metabolites within 48-72 hours. 2-16% is excreted in the feces within 72 hours. There are no data on the excretion of the drug in breast milk.

Indications

The main indications are germinogenic testicular and ovarian tumors and lung cancer. Etoposide has been reported to be effective in the treatment of bladder cancer gastric cancer adrenal cortical cancer non Hodgkin’s lymphogranulomatosis acute monoblastic and myeloblastic leukemia Ewing’s sarcoma trophoblastic tumors Kaposi’s sarcoma and neuroblastoma.

Use during pregnancy and lactation

Contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding.

Contraindications

-Hypersensitivity to etoposide or excipients;

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

Severe liver function disorders;

Acute infections;

Pregnancy and lactation.

With caution:

renal failure alcoholism epilepsy; childhood (safety and efficacy for children under 2 years of age have not been established).

Side effects

From the hematopoietic system: a decrease in the number of white blood cells and granulocytes depends on the administered dose and is the main dose-limiting toxic manifestation of Etoposide-LANCE®. 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 use of Etoposide-LANCE®. Recovery of blood counts usually occurs on the 20th day after the standard dose is administered. Anemia is rare.

From the digestive system: nausea and vomiting occur in approximately 30-40% of patients are moderate in nature and usually do not lead to drug withdrawal. Antiemetic medications 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. 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 fluid and other maintenance therapy is administered. If it is necessary to resume use of the drug, the rate of use should be reduced.

Allergic reactions: chills fever tachycardia bronchospasm shortness of breath and low blood pressure. These reactions are usually observed during or immediately after etoposide use and stop when the infusion is stopped and glucocorticosteroids or antihistamines are used.

From the skin: reversible alopecia, sometimes leading to complete hair loss, occurs in 66% of patients. Rarely-pigmentation pruritus recurrent radiation dermatitis.

Local reactions: phlebitis when the drug gets under the skin – a pronounced local irritant effect up to necrosis of the 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 vision muscle cramps metabolic acidosis hyperuricemia.

Interaction

The antitumor effect of etoposide is enhanced when used in combination with cisplatin (it should be borne in mind that etoposide excretion may be impaired in patients previously treated with cisplatin).

Etoposide should not be mixed with other medicinal products in the same solution Pharmacologically incompatible with solutions with alkaline pH values.

Due to the immunosuppressive effect of the drug and the possibility of developing a severe infection, it is not recommended to use live vaccines during chemotherapy. Vaccination should be carried out 3 months after the end of therapy.

How to take, course of use and dosage

When choosing the route of use of the regimen and doses in each individual case, you should be guided by the data of the specialized literature.

The dosage regimen is set depending on the chemotherapy regimen used (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). Etoposide-LANCE® is administered intravenously by drip for 30-60 minutes in the following doses:

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

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

In patients with impaired renal function (creatinine clearance 15-50 ml/min), the dose of etoposide should be reduced by 25%. With creatinine clearance

Repeated courses are carried out only after normalization of peripheral blood parameters.

Before intravenous use, Etoposide-LANCE® is diluted in 250 ml of 09% sodium chloride solution or 5% dextrose solution to a final concentration of 02-04 mg / ml. Avoid contact with buffer aqueous solutions with a pH above 8.

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

Precautions for use

Etoposide-LANCE® should only be used under the constant supervision of a physician with experience in the treatment of cytotoxic drugs.

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

Suppression of bone marrow function is a dose-limiting toxicity. Regular monitoring of blood composition should be carried out before starting treatment in breaks and before each subsequent course of the drug. If radiation therapy and/or chemotherapy have been performed prior to Etoposide-LANCE therapy, the dosage regimen should be selected taking into account the severity of bone marrow suppression.

If the platelet count drops below 50,000/µl and/or the absolute neutrophil count drops to 500/µl, therapy should be discontinued until the blood counts are fully restored.

– If anaphylactic reactions occur, the use of Etoposide-LANCE® should be discontinued and treatment with endocorticosteroids and/or antihistamines should be initiated against the background of infusion therapy.

-If signs of extravasation appear, Etoposide-LANCE ® infusion should

be stopped immediately. The remaining drug is injected into another vein.

Subcutaneous hydrocortisone injections are performed around the affected area and 1% hydrocortisone ointment is applied under a dry bandage (until the skin hyperemia disappears – usually for 24 hours).

Patients with hepatic or renal insufficiency need to adjust the dosage regimen and regularly monitor kidney and liver function.

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

Rarely, patients receiving Etoposide-LANCE® therapy in combination with other antitumor drugs may develop acute leukemia with or without a pre-leukemic phase.

Etoposide-LANCE® solution for intravenous use as a filler contains ethyl alcohol which may be a risk factor for patients suffering from liver diseases alcoholism epilepsy and children.

Overdose

The main suspected manifestations of overdose are myelosuppression and toxic effects from the gastrointestinal tract. Treatment is symptomatic. The specific antidote is not known.

Special instructions

Influence on the ability to drive vehicles and mechanisms:

Depending on individual sensitivity, etoposide may impair the ability to drive vehicles and mechanisms.

Storage conditions

At a temperature of 15 to 30° C, keep out of the reach of children.

Shelf

life is 3 years.

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

Active ingredient

Etoposide

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution