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

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 G- 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, in saliva, liver tissue, spleen, kidneys, myometrium, brain tissue. Etoposide penetrates the blood-brain and

placental barriers. The concentration of etoposide in the cerebrospinal fluid varies from undetectable values to 5% of the concentration in the blood plasma. Data on the isolation of the drug with breast milk are absent. The binding to plasma proteins is approximately 97%.

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 between 5.3 and 10.8 hours.

Etoposide is excreted in the urine in the form of unchanged substance (29%) and metabolites (about 15%) for 48-72 hours. 2-16% is excreted with feces.

Indications:

The main indications for the use of Phytoside are germinogenic tumors of the testicle and ovaries, lung cancer.

There are reports of the effectiveness of phytoside 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. Myelosuppression (neutrophil count below 1500 / μL and / or platelets below 75,000 / μL).

- Pronounced violations of the liver.

- Acute infection.

- Pregnancy and lactation.

Carefully:

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

Pregnancy and lactation:contraindicated

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 individually, 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, phytoside is administered for 30-60 minutes, with doses generally being 50-100 mg / m² per day for 4-5 days, with repetition of cycles every 3-4 weeks.

Also, the mode of administration of Phytoside every other day is 100-125 mg / m² on days 1, 3 and 5.

Repeated courses are held only after the normalization of peripheral blood.

Before intravenous injection, Phytoside diluted 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.

Side effects:

From the hematopoiesis: the reduction in the number of leukocytes and granulocytes depends on the administered dose and is the main dose limiting toxic manifestation of Veropenoposide. 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, and the maximum decrease in platelets is observed 9-16 days after the administration of etoposide. Recovery of blood values occurs usually on day 20 after the administration of a standard dose. Anemia is rare.

From the digestive system: nausea and vomiting occurs 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, there was diarrhea, abdominal pain, stomatitis, esophagitis, dysphagia, anorexia. Sometimes there is a temporary hyperbilirubinemia and an increase in the level of transaminases. Most often, this happens when doses exceeding recommended levels are used.

From the cardiovascular system: with rapid intravenous administration, a temporary decrease in blood pressure was noted in 1-2% of patients, which is usually restored by stopping infusion and injecting fluids or other maintenance therapy. If the need to restart the introduction of Phytoside, the rate of administration should be reduced.

Allergic reactions: symptoms reminiscent of anaphylactic, such as chills, fever, tachycardia, bronchospasm, shortness of breath and lowering blood pressure. These reactions are usually observed during or immediately after the administration of etoposide and cease upon discontinuation of infusion and the use of glucocorticosteroids or antihistamines.

Dermatological reactions: reversible allopecia, 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 toxic effects:

Occasional peripheral neuropathy, drowsiness, fatigue, residual taste in the mouth, fever, interstitial pneumonitis / pulmonary fibrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, optic neuritis, transient blindness of cortical genesis, muscle cramps, metabolic acidosis, hyperuricemia, phlebitis with intravenous administration. If the product gets under the skin - a pronounced local-irritant effect up to the necrosis of surrounding tissues.

Overdose:The cases of overdose in the application of ztoposide in humans have not been recorded to date. It can be assumed that the main manifestations of an overdose would be toxic effects from the blood and gastrointestinal tract. In such cases, mainly symptomatic therapy is indicated. Specific antidotes do not exist.

Interaction:

The antitumor effect of etoposide is enhanced when it is used in combination with cisplatin, however, it should be borne in mind that in patients who have previously received treatment with cisplatinum, excretion of etoposide may be impaired.

Etoposide should not be mixed with other drugs in a single 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:

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

- When working with Phytoside, 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 action of Veropoeposide. Regular monitoring of the blood composition should be performed before the beginning of treatment, in breaks and before each subsequent course.If radiotherapy and / or chemotherapy were used before the initiation of therapy with Phytoside, a sufficient interval between these two treatments should be observed to ensure the restoration 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.

- When anaphylactic reactions occur, the introduction of Phytoside must be stopped and treatment with corticosteroids and / or antihistamines should be started against the background of infusion therapy.

- If an accidental extravasation is introduced, 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.

- Precautions should be taken when administering the drug to patients with hepatic or renal insufficiency.

- Men and women receiving therapy with Phytoside should use reliable methods of contraception.

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

- Before use, use a visual assessment of the solution for solids or discoloration.

- Phytoside concentrate 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 for children.

Form release / dosage:Concentrate for the preparation of a solution for infusions in bottles of colorless glass at 100 mg / 5 ml.

Packaging:Concentrate for the preparation of a solution for infusions in bottles of colorless glass at 100 mg / 5 ml. For 1 bottle in a cardboard box with the attached instructions for use.

Storage conditions:

List B. Store at a temperature of up to 25 ° C in a place protected from light and inaccessible to children. Do not freeze.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:P N 015946/01

Date of registration:05.10.2009

The owner of the registration certificate:Fresenius Kabi Deutschland GmbHFresenius Kabi Deutschland GmbH Germany

Manufacturer: & nbsp

FRESENIUS KABI ONCOLOGY, Limited India

Representation: & nbspFRESENIUS KABI DEYCHLAND GmbH FRESENIUS KABI DEYCHLAND GmbH Germany

Information update date: & nbsp15.10.2015

Illustrated instructions

Instructions

Phytoside (Fytosid)