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Etoposide is a semisynthetic derivative of podophyllotoxin. The mechanism of action is associated with inhibition of topoisomerase II. Etoposide exerts a cytotoxic effect due to DNA damage. The drug blocks mitosis, causing cell death in the late G2 phase and S-phase mitoticheckogo cycle. High concentrations of the drug in causing cell lysis premitoticheckoy phase.
Etoposide nucleotides also primobolan steroid suppresses infiltration through plasma membrane, preventing DNA synthesis and recovery

Pharmacokinetics
When administered etoposide is absorbed from the gastrointestinal tract. Bioavailability is an average of 50% and it is not changed depending on food intake.
The drug is found in plevralnoy- fluid, saliva, liver, spleen, kidney, myometrium, brain tissues. Etoposide penetrates the blood-brain and placental barriers. Values of etoposide concentration in cerebrospinal fluid ranging from undetectable levels up to 5% of the plasma concentration. Data on the allocation of the drug in breast milk are not available. Plasma protein binding is approximately 90%.
Etoposide is extensively metabolised in the body. Isolation of etoposide is then carried out a two-phase process. In adults with normal liver and kidney function in the half-life averages approximately 0.6 – 2 hours with a half-life in the final phase in the range of 5.3 – 10.8 hours. In children with normal renal function and liver Etoposide half-life is on average in the initial phase of 0.6 – 1.4 hours, and in the final phase – 3 -. 5.8 hours
Etoposide is excreted in the urine as unchanged substance (29%) and metabolites (approximately 15%) for 48-72 hours. 2-16% is excreted in the feces.

Indications
The main indications for the use of Etoposide are germ cell tumors of the testis and ovary, lung cancer.
There are reports on the effectiveness of Etoposide in the treatment of bladder cancer, Hodgkin’s disease, non-Hodgkin’s lymphoma, acute monoblastny and myeloid leukemia, Ewing’s sarcoma, trophoblastic tumors, gastric cancer, sarcoma sarcoma and neuroblastoma.

Dosage and administration
Dosage is determined individually, depending on the chemotherapy regimens. When administered etoposide administered at 50 mg / m 2 daily for 14-21 days, with repetition of cycles every 28 days, or 100-200 mg / m 2 for 5 consecutive days every 3 weeks.
Repeated courses are held only after normalization of peripheral blood. When selecting the dose should take into account the effect of other myelosuppressive drugs in combination, and the effect of prior radiation therapy and chemotherapy.

Side effect

From hemopoiesis system: decrease in the number of white blood cells and granulocytes dose-dependent and is the main dose-limiting toxicities Etoposide. Maximum reduction in the number of granulocytes usually occurs 7-14 days after the injection. Thrombocytopenia occurs less frequently, and the maximum reduction of platelets is observed in 9-16 days after administration of etoposide. Restoration of blood parameters usually occurs on day 20 after administration of a standard dose. Anaemia occurs infrequently.

From the side, the digestive system: nausea and vomiting occurs in approximately 30-40% of patients. Usually, these effects are mild in nature, and to resort to the cancellation of the treatment because of them it is rarely necessary. To control these side effects shown antiemetics. In addition, the observed diarrhea, abdominal pain, stomatitis, esophagitis, dysphagia, anorexia. Sometimes primobolan steroid there is a slight temporary hyperbilirubinemia and increased transaminases. Most often it occurs at doses higher than recommended.

Cardio-vascular system: With the rapid intravenous injection of 1-2% of patients showed a temporary decrease in blood pressure, which is usually recovered at the termination of the infusion and administration of fluids or other supportive therapy. If necessary, renewed administration Etoposide injection speed should be reduced.

Allergic reactions: Symptoms resembling anaphylactic such as chills, fever, tachycardia, bronchospasm, and dyspnea.

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

Other toxic effects: Occasionally observed, peripheral neuropathy, somnolence, povyshennaya ytomlyaemoct – residual taste in the mouth, fever, transient cortical blindness genesis, muscle cramps, metabolic acidosis, hyperuricemia.

Contraindications

  • Hypersensitivity to etoposide or excipients;
  • Severe myelosuppression;
  • Severe renal dysfunction of the liver;
  • Acute infections;
  • Pregnancy and lactation.

The use in children. The safety and efficacy of children has not been established.

Interactions with other drugs
Antitumor effect of Etoposide is enhanced when administered in combination with cisplatin, but it should be borne in mind that in patients previously treated with cisplatin, etoposide excretion may be impaired.
When combined with cyclosporine elimination half-life of etoposide doubles .

Overdose
No cases of overdose with the use of etoposide in humans has not yet been registered. It can be assumed that the main manifestations of overdose would be toxic effects from the blood and gastrointestinal tract. In such cases, it is shown mainly symptomatic therapy. A specific antidote is not known.

Warnings and Precautions

  • Etoposide should only be used under constant supervision of a physician with experience in therapy with cytotoxic drugs.
  • When working with primobolan steroid etoposide should follow the rules of treatment with cytotoxic drugs. In case of contact with the skin or mucous membrane of the affected area should immediately wash with soap and water.
  • Bone marrow suppression is the dose-limiting effect of etoposide. Regular monitoring of the composition of the blood should be carried out before starting treatment, during breaks and before each subsequent course of Etoposide. If prior to initiating therapy etoposide carried out radiotherapy and / or chemotherapy, you should ensure there is sufficient spacing between these two types of treatment to ensure the restoration of bone marrow function. In case of decrease in platelet count below 50,000 / mm 3 and / or absolute neutrophil count to 500 / mm 3 treatment should be discontinued until the full restoration of blood parameters.
  • In the event of anaphylactic reactions reception Etoposide must stop and start treatment with corticosteroids and / or antihistamines on the background of infusion therapy.
  • Use caution when administering the drug to patients with hepatic or renal insufficiency.
  • Men and women receiving etoposide therapy should use reliable methods of contraception.
  • Occasionally patients receiving etoposide in combination with other anticancer drugs, may develop acute leukemia, a phase predleykoznoy with and without it.

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