Etoposide
When ATH:
L01CB01
Characteristic.
The antitumor agent of plant origin, semisynthetic derivative of podophyllotoxin. It is soluble in methanol and chloroform, insignificantly soluble in ethanol, it is soluble in water and ether.
Pharmacological action.
Antitumor.
Application.
Small cell lung cancer, ovarian and testicular tumors, non-Hodgkin's lymphoma, limfogranulematoz, stomach cancer.
Contraindications.
Hypersensitivity, severe myelosuppression (leukopenia less than 2 109/l, thrombocytopenia less than 75 109/l), acute infections, kidney and / or liver failure.
Restrictions apply.
Alcoholism, epilepsy, childhood (safety and effectiveness in children have not identified).
Pregnancy and breast-feeding.
Contraindicated in pregnancy (possible mutagenic, teratogenic, carcinogenic effects).
Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)
At the time of treatment should stop breastfeeding (unknown, Do etoposide penetrates into breast milk).
Side effects.
In pooled data from different studies, involving 2081 patient, etoposide prepared as monotherapy inwards, and / in using different dosing regimens in the treatment of various malignancies, The following side effects observed.
Hematologic toxicity: leukopenia less than 1 109/l (3–17%), leukopenia less than 4 109/l (60–91%), thrombocytopenia less than 50 109/l (1–20%), thrombocytopenia less than 100 109/l (22–41%), anemia (0–33%).
Myelosuppression is dose-dependent and dose-limiting effect. In the case of the maximum reduction of leukopenia granulocyte typically observed 7-14 days after administration. The lowest level of platelets observed after 9-16 days after administration. Recovery of the bone marrow is usually the 20th day. On a cumulative myelosuppression have been reported.
It has been observed rare cases of acute leukemia (both predleykoznoy phase, and without it) patients, receiving etoposide alone or in combination with other anticancer drugs.
Gastrointestinal toxicity: nausea and vomiting (31–43%), abdominal pain (0–2%), anorexia (10–13%), diarrhea (1–13%), stomatitis (1–6%), gepatotoksichnostь (0–3%), incl. transient hyperbilirubinemia, increased liver transaminases.
Nausea and vomiting - the most frequently occurring side effects are usually mild or moderate severity, requiring discontinuation of treatment in 1% patients, usually slightly more pronounced after oral administration, rather than at / introduction. To control these side effects are shown antiemetics.
Gipotenziya: (1–2%).
After a quick on / in the observed transient hypotension, not associated with cardiotoxicity or ECG changes. To prevent this complication is recommended infusion of etoposide slowly (30-60 min). In the event of hypotension usually stop infusion and inject liquid or carry out other maintenance therapy. With the resumption of the introduction of the infusion rate should be reduced.
Allergic reactions: (1–2%).
Anaphylactoid reactions: chills, fever, tachycardia, bronchospasm, shortness of breath and/or decrease ad — were observed in 0.7-2% of patients when in/with the introduction of etoposide and ≤ 1% of patients with ingestion. These reactions usually occurred during or immediately after the administration of etoposide (cm. Precautions). It was also reported cases of hypertension and / or flares. Normalization AD usually occurs within a few hours after discontinuing the infusion etoposide.
Sometimes there is swelling of the face or tongue, cough, profuse sweating, cyanosis, squeezing sensation in the throat, laringospazm, backache, loss of consciousness. On the occurrence of apnea, associated with hypersensitivity, It reported rarely. In rare cases, anaphylaxis can be fatal.
Dermatological reactions: obratimaya alopecia (8–66%), sometimes resulting in a complete loss of hair. When used in recommended doses may experience rashes, urticaria and / or itching. When used in doses of etoposide, are in the research stage, It reported on the development of generalized itchy erythematous maculopapular rash, accompanied perivaskulitom.
Other toxicities. Peripheral neurotoxicity (1–2%). Occasionally observed: residual taste in the mouth, fever, pigmentation, dysphagia, blindness korkovogo genesis; relapse radiation dermatitis (1 event), metabolic acidosis, toxic effect on the CNS (unusual tiredness, difficulty in walking, numbness or tingling in fingers and toes, weakness), muscle cramps, hyperuricemia; phlebitis (pain at the injection site), in contact with the skin - marked local irritating effect.
Cooperation.
In case of simultaneous or sequential use of drugs, causing depression of bone marrow function, or radiation therapy increases the risk of myelosuppression. The treatment effect of etoposide may decrease inactivated viral vaccines, and may increase side effects in live virus vaccines. Pharmaceutically compatible with solutions, having alkaline pH values.
Overdose.
Symptoms: increased toxicity (hematological, from the gastrointestinal tract).
Treatment: simptomaticheskaya therapy. Spetsificheskiy antidote unknown.
Dosing and Administration.
B / drop, inside. The mode set individually, depending on the evidence, stage of the disease, the state of the hematopoietic system and regimens.
Precautions.
Treatment should be a doctor, with experience of chemotherapy, and if the conditions, needed for the relief of complications of treatment (sterilynыy box, sufficient arsenal of antibiotics, the possibility of substitution therapy with blood components).
Be wary of hypoalbuminemia (may increase the risk of the toxic effect of etoposide).
Hypersensitivity reactions may occur after the first injection. In case of such reactions (chills, fever, tachycardia, bronchospasm) you must stop using the product and begin treatment with corticosteroids and / or antihistamines, and conduct other maintenance treatment.
Before the beginning, during treatment and before each subsequent course requires monitoring of peripheral blood. In case of a decrease in the number of platelets below 50 109/l and / or absolute number of neutrophils up to 0.5 109/l therapy should be discontinued.
In patients who develop thrombocytopenia as a result of the treatment is necessary to exercise extreme caution when performing invasive procedures and dental procedures. Such patients need regular inspection of places on / in the, skin and mucous membranes (for signs of bleeding), limit frequency troublesome and the rejection of the / m injection, control of blood in the urine, vomit, Kale. Such patients should be carefully shave, manicure, brush your teeth, dentists use threads and toothpicks, to carry out prevention of constipation, avoid falls and other injuries, as well as the intake of alcohol and aspirin, increase the risk of gastrointestinal bleeding.
Due to the possible risk of infectious diseases to patients who develop leukopenia may require antibiotics. It is necessary to postpone the vaccination schedule and the patient living with him family members (conduct after 3-12 months after the last cycle of chemotherapy), should abandon immunization oral polio vaccine.
Avoid introduction extravasal (expressed as a result of irritation to the surrounding tissue). In case of accidental introduction of extravasal discontinue injection and continue the introduction of another vein (administration stopped as soon as a burning sensation). Around the affected area is carried out by subcutaneous injection of hydrocortisone and bandage with 1% hydrocortisone ointment to the disappearance of erythema (usually 24 no).
Women and men of reproductive age should use reliable methods of contraception. Women should immediately inform your doctor about the alleged pregnancy.
Cautions.
Medical staff are encouraged to work with the preparation gloves (in contact with the skin can cause rashes). In case of contact with the skin or mucous membranes of the affected areas immediately with soap and water.
Ethanol in the etoposide solution composition for in / administration may be a risk factor for patients, suffering from liver disease, alcoholism, epilepiey, as well as for children.
