Lustette - instructions for use, dose, side effects, contraindications

Ingredients Active substance:	Amount in 1 ampoule / vial (5 ml)	Composition per 1 ml
Etoposide	100 mg	20 mg
Excipients:
Polysorbate-80	400 mg	80
Lemon acid	10 mg	2
Macrogol-400	3000 mg	600
Ethanol	1515 mg	303

Description:Transparent slightly viscous liquid of light yellow color.

Pharmacotherapeutic group:Antitumor agent, alkaloid

ATX: & nbsp

L.01.C.B.01 Etoposide

Pharmacodynamics:

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 G2 phase 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 peak plasma concentration is 30 μg / ml. The drug is found in the pleural fluid, liver tissue, spleen, kidneys, myometrium. Etoposide penetrates the placental barrier. The concentration of etoposide in the cerebrospinal fluid varies from undetectable values to 5% of the concentration in the blood plasma. There are data on the isolation of the drug with breast milk. Binding to plasma proteins is approximately 90%.

Etoposide is actively metabolized in the body. Isolation of etoposide is carried out in a two-phase way. In adults with normal renal and hepatic function, the half-life on average is approximately 0.6-2 hours with a half-life in the final phase within 5.3-10.8 hours. In children with normal renal and hepatic function, the half-life of etoposide is about 0.6 to 1.4 hours on average in the initial phase and 3 to 5.8 hours in the final phase.

Etoposide is excreted by the kidneys in the form of unchanged substance (29%) and metabolites (about 15%) for 48-72 hours. 2-16% is secreted through the intestine.

Indications:

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

There are reports of the effectiveness of etoposide in the treatment of bladder cancer, 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;

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

Pronounced violations of the liver and kidneys;

Acute infections;

Pregnancy and lactation.

Carefully:

Hypoalbuminemia (possibly increased risk of toxic effects of etoposide), renal failure of mild to moderate severity, parasitic and infectious diseases of viral, fungal or bacterial nature, alcoholism, epilepsy, elderly patients, childhood (because the drug is ethanol).

Pregnancy and lactation:Contraindicated in pregnancy and the period of breastfeeding.

Dosing and Administration:

Intravenously.

The dosage regimen is set individually, depending on the chemotherapy regimen used.

Intravenously etoposide is administered within 30-60 minutes, with the dose of etoposide usually 50-100 mg / m for 4-5 days, with repeated cycles every 3-4 weeks. Also, the regimen of etoposide administration every other day is 100-125 mg / m² in the 1 st, 3 rd and 5 th days. 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 intravenous injection etoposide diluted with 250 ml of 0.9% sodium chloride solution or 5% dextrose solution to a final concentration of 0.2-0.4 mg / ml. The resulting solution should be used immediately after preparation. Do not allow contact with buffer aqueous solutions with pH> 8.

For 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.

Side effects:

On the part of the hematopoiesis system: Reducing the number of leukocytes and granulocytes depends on the dose administered and is the main dose limiting toxic manifestation 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 frequently; the maximum decrease in platelets is observed on the 9-16th day after the administration of etoposide. Recovery of blood counts is usually on the 20th day after the introduction of the standard dose. Anemia can occur.

From the digestive system: Nausea and vomiting occur in about 30-40% of patients. Usually, these phenomena are of a moderate nature, and resort to cancellation of treatment because of them is rare. To control these side effects, antiemetic drugs are indicated. In addition, diarrhea, abdominal pain, stomatitis, esophagitis, dysphagia, anorexia, constipation, dysgeusia, mild temporary hyperbilirubinemia and increased activity of "liver" transaminases were noted. Most often, this occurs when the recommended dosage is exceeded.

From the side of the cardiovascular system: With rapid intravenous administration, a temporary decrease in blood pressure was noted in 1-2% of patients, which usually recovers when the infusion is discontinued and fluids or other maintenance therapy is given.If it is necessary to resume the administration of etoposide, the rate of administration should be reduced. There were rare cases of arrhythmia.

Allergic reactions: Symptoms reminiscent of anaphylactic, such as chills, fever, tachycardia, bronchospasm, shortness of breath and lowering blood pressure.

From the skin: Reversible alopecia, sometimes leading to complete loss of hair, occurs in at least 66% of patients. Rarely is the appearance of pigmentation, itching. In one case, there was a relapse of radiation dermatitis.

Other: Occasional peripheral neuropathy, drowsiness, fatigue, metallic taste in the mouth, mucositis, interstitial pneumonitis / pulmonary fibrosis, skin rash, urticaria, malignant exudative erythema (Stevens-Johnson syndrome), fever, transient blindness of cortical genesis, muscle cramps, metabolic acidosis, hyperuricemia, "hot flashes". If the product gets under the skin - a pronounced local irritant effect, phlebitis, toxic epidermal necrolysis (Lyell's syndrome), optic neuritis.

Local Reactions: Phlebitis, when the drug gets on the skin - a pronounced local irritant effect up to the necrosis of surrounding tissues.

Overdose:

Symptoms: there have been no cases of overdose with etoposide in humans until now. It can be assumed that the main manifestations of an overdose would be toxic effects from the blood and digestive system.

Treatment: symptomatic therapy. The specific antidote is not known.

Interaction:

The antitumor effect of etoposide increases with its use in combination with cisplatin, but it should be noted that in patients previously treated with cisplatin, the excretion of etoposide may be impaired.

When combined with cyclosporine, the half-life of etoposide is doubled.

Etoposide also enhances the effect of oral anticoagulants.

The mutual enhancement of the therapeutic effect between etoposide and a number of cytostatic agents (for example, methotrexate and cisplatin) has been established. Etoposide enhances the cytotoxic and myelosuppressive effect of other drugs.

Phenylbutazone, sodium salicylate and salicylic acid can affect the binding of etoposide with blood proteins.

Experimentally, cross-resistance between anthracycline and etoposide was also demonstrated.

Etoposide should not be mixed with other drugs in a single solution. The drug is pharmaceutically incompatible with solutions having alkaline pH values, and there is also the risk of precipitation when dissolved in buffer solutions with pH> 8.

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.

Etoposide increases (mutually) the toxicity of immunosuppressive drugs (cyclophosphamide, fluorouracil, vinblastine, doxorubicin and etc.).

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 the dose-limiting effect of etoposide. Regular monitoring of the blood composition should be performed before the beginning of treatment, in breaks and before each subsequent course of etoposide. If radiation therapy and / or chemotherapy has been performed prior to initiating therapy with etoposide, then a sufficient interval between these two treatments should be observed to ensure the restoration of bone marrow function. In the case of a decrease in the number of platelets below 50000/mm³ and / or absolute number of neutrophils to 500 / mm³ Therapy must be discontinued until the blood counts are fully restored.

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

- If extravasation occurs, stop the injection immediately and insert the remaining portion into another vein. The introduction is discontinued as soon as a burning sensation appears. Around the affected area, subcutaneous hydrocortisone injections are administered and 1% hydrocortisone ointment is applied (until the erythema disappears) under a dry bandage 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 receiving therapy with etoposide should use reliable contraceptive methods during the treatment period, and also within 6 months after the end of chemotherapy. Due to the possibility of the development of irreversible loss of fertility as a result of treatment with etoposide, patients should be given a recommendation on the preservation of sperm before the beginning of the course of treatment with the drug Lusteth;

- During treatment, the risk of infectious diseases and bleeding increases. Patients should be warned about the possibility of nausea and the reversibility of baldness resulting from therapy.

- Occasionally, patients receiving therapy with etoposide in combination with other antitumor drugs may develop acute leukemia, either with or without the podleicosis phase.

Before use, visually assess the solution for solids or discoloration.

The Lustette solution for intravenous administration as an excipient contains ethyl alcohol, which can be a risk factor for patients suffering from liver disease,alcoholism, epilepsy, and also for children.

Effect on the ability to drive transp. cf. and fur:In the event of such side effects as nausea, low blood pressure, drowsiness, you should refrain from driving and other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

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

Packaging:

5 ml in a sealed ampoule with a capacity of 6 ml of neutral glass (type 1), marked with two rings and a blue point.

5 ml in bottles of neutral glass, ukuporennyh cover made of plastic red color with the inscription "Lastet 100 mg / 5 ml" in Japanese.

For 10 ampoules in a cardboard pallet together with instructions for use in a cardboard bundle.

For 10 bottles in the foam polystyrene tray together with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature of 5 to 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N014897 / 02

Date of registration:01.07.2008 / 26.12.2014

Expiration Date:Unlimited

The owner of the registration certificate:Nippon Kayaku Co., Ltd.Nippon Kayaku Co., Ltd. Japan

Manufacturer: & nbsp

NIPPON KAYAKU, CO. Ltd. Japan

Representation: & nbspCompany FARMSTOR, LLCCompany FARMSTOR, LLC

Information update date: & nbsp12.03.2018

Illustrated instructions

Instructions

Lusteth (Lastet)