Dactinomycin
When ATH:
L01DA01
Characteristic.
The main component of the mixture actinomycins, produtsiruemoy Streptomyces parvullus. Lyophilized powder yellow. It is soluble in water at a temperature from +8 ° C to 10 °C. Practically insoluble at a temperature 37 °C. Molecular weight 1255,43.
Pharmacological action.
Antitumor, Antibacterial, antifungal.
Application.
Wilms' tumor (in combination with radiation therapy), raʙdomiosarkoma (in combination with vinkristinom and tsiklofosfamidom), metastatic choriocarcinoma (in combination with methotrexate controlled hCG level), nonmetastatic choriocarcinoma (in combination with methotrexate and surgery), metastatic carcinoma of the testes, sarkoma Juinga (in the complex therapy), grozdevidnaya sarcoma (in combination with radiation therapy), ovarian and uterine cancer, sarkomы (Kaposi, osteogenic), melanoma.
Contraindications.
Hypersensitivity, suppression of bone marrow function, enable vetryanaya, herpes zoster, abnormal liver function, age 6-12 months.
Restrictions apply.
Gout or renal calculi in history (the risk of hyperuricemia), prior cytotoxic or radiation therapy, pregnancy, lactation, older than 6-12 months.
Pregnancy and breast-feeding.
Not recommended during pregnancy because of the potential risk to the fetus (dactinomycin crosses the placenta, mutagenic, teratogenic and carcinogenic effects). In the case of pregnancy or during planned pregnancy must notify the patient of the potential risk to the fetus.
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.)
Nursing women should decide the issue of termination of breastfeeding (unknown, Does dactinomycin passes into breast milk. Many drugs are excreted in breast milk of women, there is a potential risk of adverse effects).
Side effects.
Cardio-vascular system and blood (hematopoiesis, hemostasis): anemia (until aplastic), leukopenia, thrombocytopenia; less frequently - pancytopenia, agranulocytosis and retikulopeniya, unusual bleeding or hemorrhage.
From the digestive tract: nausea, vomiting, diarrhea (observed during the first hours after injection and can last 4-20 h), esophagitis, erosive and ulcerative gastrointestinal lesions, proctitis; less frequently - ulcerative stomatitis, pharyngitis, cheilitis, dysphagia, abdominal pain; rarely is the hepatotoxicity, incl. ascites, gepatomegaliya, hepatitis, change in liver function tests.
With the genitourinary system: rarely - hyperuricemia, nephropathy (associated with increased production of uric acid).
For the skin: alopecia (usually begins 7-10 days after administration, may include the scalp and eyebrows skin), acne, recurrent erythema or increased pigmentation of the skin, previously irradiated.
Allergic reactions: skin rash, rare - anaphylaxis.
Other: unusual tiredness, fever, myalgia, hypocalcemia, rarely - extravasates, cellulitis, phlebitis (pain at the injection site), soft tissue necrosis (in contact with the skin).
Cooperation.
Other anticancer drugs and radiation therapy to potentiate the effect. May enhance the cardiotoxic effects of doxorubicin, weaken the effect of vitamin K.
Overdose.
Symptoms: nausea, vomiting, diarrhea, stomatitis, GI ulcers, pronounced inhibition of hematopoiesis, acute renal failure, possible death.
Treatment: symptomatic and supportive. It recommended for frequent monitoring of renal function, liver and bone marrow.
Dosing and Administration.
B /, pre-diluted with sterile water for injection (without preservatives); infusion solution can be prepared additionally dilute 5% glucose solution or 0,9% sodium chloride solution. The maximum daily dose for adults and children - 15 ug / kg or 400-600 mg / m2 body surface during 5 days. An alternative course for children - the total dose 2,5 mg / m2 for 1 Sun. A second course for children, and for adults it may be carried out not earlier than 3 Sun (provided disappearance of all signs of toxic effects).
Wilms tumor When using a combination of low-dose radiotherapy and, possible combination therapy with vincristine (during 7 cycles, duration of maintenance therapy - 15 Months) together with surgery and radiotherapy. When rhabdomyosarcoma recommended following combinations: vincristine and dactinomycin, vynkrystyn, dactinomycin and cyclophosphamide (VAC-therapy). Children with inoperable or metastatic rhabdomyosarcoma prescribed VAC-therapy. When metastatic choriocarcinoma applied sequentially dactinomycin and methotrexate, with non-metastatic - as dactinomycin and methotrexate (together and separately) in combination with surgery or without. In metastatic carcinoma of the testes prescribed cycles of 0,5 mg / day 5 consecutive days every 6-8 weeks during the 4 months or more. When Ewing sarcoma using a consistent assignment of dactinomycin - 45 mg / m2 and cyclophosphamide - 1200 mg / m2 in conjunction with radiation therapy for 18 Sun. When acinar sarcoma is administered in combination with radiation therapy.
Precautions.
The use of dactinomycin should be under strict control of blood parameters. Inhibition of bone marrow occurs in about 7-10 days after the treatment with the lowest level of blood cells through 3 Sun (restored after about 3 Sun). When a marked decrease in the number of platelets and leukocytes treatment is stopped to restore bone marrow function. Should systematically determine the activity of liver enzymes, bilirubin, conduct a general analysis of urine. In the calculation of the dose for patients, obese or swelling, It should take into account an ideal body weight. In the course of treatment is recommended to avoid contact with infectious patients, use adequate contraceptive measures and to use caution when using toothbrushes, threads or toothpicks. The emergence of unusual bleeding or hemorrhage, degteobraznogo black stool, blood in the urine or feces or point red spots on the skin, as well as signs of infection requires immediate medical consultation. During the period of treatment is not recommended vaccination virus vaccines (when administered during treatment with live virus vaccines may increase replication of the vaccine virus and the strengthening of its side effects, Inactivated vaccines - reducing production of antiviral antibodies). Nausea and vomiting, which develop during the first hours after administration, possible to stop antiemetics. In case of contact with the skin or in the tissue to be interrupted and the infusion system disconnect for / in the, but leave the cannula / needle in place. After extraction through a cannula / needle drug effused (antidote is administered if necessary - sodium thiosulfate) you can remove the cannula / needle. Limbs should be given the elevated position and apply a cold compress on 45 m. In preparing the solution should avoid inhaling the powder and fumes, contact with the skin and mucous membranes (especially eye). In case of eye contact with the drug should be immediately rinsed with plenty of water and consult an ophthalmologist. Skin contact should be flushed contaminated surface with plenty of water during 15 m. If the drug is injected directly into a vein without the infusion system, It should be applied "Two needle" technique: to dissolve and remove the calculated dose from the vial using a sterile needle, and enter - other. It will be appreciated, that the joint radiotherapy increases the risk of toxic effects on the gastrointestinal tract and bone marrow suppression. With the utmost care appoint during a two-month treatment of right-sided Wilms' tumor, tk. while noting hepatomegaly and elevated AST.
Cautions.
Application dactinomycin should be performed in compliance with specified safety precautions during preparation and dilution of injectable solutions (in a sterile box with the use of disposable surgical gloves and masks) and disposal of needles, syringes, bottles, ampoules and the remainder of the unused product. For the prevention of hyperuricemia possible use of allopurinol. Distorts the results of biological samples, used to determine the efficacy of antimicrobials.
