Composition, form of production and packaging
A solution for intravenous administration and perfusion in the form of a transparent liquid of golden color.
dactinomycin 500 mcg
Excipients: 10% dextran solution with a molecular weight from 3000 to 4000 in isotonic sodium chloride solution - up to 1 ml.
1 ml - ampoules of dark glass (5) - plastic containers (1) - cardboard packs.
1 ml - dark glass ampoules (10) - plastic containers (1) - cardboard packs.
1 ml - ampoules of dark glass (5) complete with scarifier - plastic pens (1) - packs cardboard.
1 ml - dark glass ampoules (10) complete with a scarifier - plastic pens (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
Antitumor antibiotic. Pharmacological action of dactinomycin is predominantly antitumoral, however, in addition, the drug has antibacterial and antifungal effect.
The mechanism of the antitumor effect of the drug is based on the formation of a complex with DNA and a violation of its matrix activity. In this case, dactinomycin intercalates between pairs of nitrogenous bases of guanine-cytosine DNA and interferes with the movement of RNA polymerase, thus violating transcription. There is information about the inhibitory effect on topoisomerase II. The antitumor effect does not depend on the phase of the cell cycle.
The drug has antibacterial effect against Gram-positive and Gram-negative bacteria and antifungal action, however, due to high toxicity (LD 50 - 0.791), it is not used as an antimicrobial agent. In addition, dactinomycin has immunosuppressive activity.
Suction and distribution
With bolus intravenous infusions, dactinomycin in adults at doses of 0.7 to 1.5 mg / m 2 C max equal to 25.1 ng / ml is observed 15 minutes after administration. The average concentration of dactinomycin after 6 hours is 2.67 mg / l.
With IV administration, the drug accumulates in nuclear cells, penetrates insignificantly through the BBB (<10%); penetrates the fetoplacental barrier. Much associated with tissue proteins.
Metabolism and excretion
Metabolized slightly. T 1/2 is 36 hours. It is excreted with bile - 50% unchanged, kidneys - 10% unchanged.
In preoperative and postoperative periods, in combination with radiotherapy:
- nefroblastoma (Wilms tumor);
non-seminiferous malignant testicular tumors;
- trophoblastic tumors;
- Locally recurrent or locally advanced solid tumors.
The drug is administered iv. Infusion administration of the drug Acnomide D В® should be carried out only in a hospital.
The dose of Acnomide D В® is selected individually, depending on the patient's tolerance of the drug, as well as on the selected program of antitumor therapy. The daily dose for both adults and children should not exceed 15 mcg / kg or 400-600 mcg / m 2 for 5-7 days.
Usually, the adult dose is 500 Ојg / day IV maximum for 5-7 days. When calculating the dose in patients with obesity or edema, the body surface area should be taken into account so that the dose corresponds to the "dry" body weight.
Children are prescribed 15 mcg / kg / day IV for 5 days.
There is an alternative course - a total dose of 2500 mcg / m 2 IV per week. For both adults and children, a second course of treatment with the drug can be carried out no earlier than 3 weeks (if all the signs of toxic effects disappear).
In nephroblastoma (Wilms tumor), the recommended dose is 15 Ојg / kg / day for 5 days iv in combination with other chemotherapeutic agents in various treatment regimens.
Also, the drug is administered intravenously intravenously for 3-5 minutes on the first day every 42 days at a dose of 45 Ојg / kg for Wilms tumor and 1.25 mg / m 2for Ewing's sarcoma .
In non-seminiferous malignant testicular tumors, the recommended dose is 1000 Ојg / m 2 IV on the first day of treatment in combination with cyclophosphamide, bleomycin, vinblastine and cisplatin.
In trophoblastic tumors, the drug is administered iv at a dose of 12 mcg / kg / day for 5 days as monotherapy and at a dose of 500 mcg on days 1, 2 as a combined regimen with etoposide, methotrexate, calcium folinate, vincristine, cyclophosphamide and cisplatin. It is possible to use combination therapy with dactinomycin and vincristine together with surgical treatment and radiotherapy, with dactinomycin and vincristine being applied for 7 cycles, so the duration of maintenance therapy is approximately 15 months.
With rhabdomyosarcoma the following combinations are used: vincristine and dactinomycin; vincristine, dactinomycin and cyclophosphamide (VAC-therapy), as well as all four drugs in series.
With thorny sarcoma, dactinomycin is prescribed at medium doses of 500 mcg / day for 5 days in combination with radiation therapy, which leads to temporary objective improvement and the disappearance of pain and discomfort.
With metastatic choriocarcinoma, sequential therapy with dactinomycin and methotrexate is used. Sequential therapy is used, if available: stability of gonadotropin titers after 2 successful courses of any of the drugs; increase gonadotropin titers during treatment; toxicity, preventing adequate therapy.
With nonmetastatic choriocarcinoma, dactinomycin and methotrexate are administered both together and separately in combination with or without surgery.
In metastatic non-seminomatous carcinoma, the testicular dactinomycin is used as monotherapy, appointing 500 Ојg / day for 5 consecutive days, every 6-8 weeks, for 4 months or more.
With nonmetastatic gestational trophoblastic neoplasia, dactinomycin at a dose of 500 mcg / day for 5-7 days is used in combination with methotrexate at 30 mg / m2 IM once a week. before the normalization of HCG titre. Intermittent courses of therapy continue to three negative results of the test for the presence of HCT, conducted 1 time / week.
With metastatic gestational trophoblastic neoplasia, treatment is carried out longer, with the same doses of dactinomycin and methotrexate. After receiving negative titers, HCT is prescribed one additional chemotherapy course. If there is resistance to methotrexate (ie there is a rise or maintain a constant level of HCG titer) or after the 5th course of chemotherapy titers are still positive, they switch to monotherapy with dactinomycin at a dose of 500 mcg / day for 7 days.
For locally recurring or locally advanced solid tumors in combination with radiotherapy, the usual dose of dactinomycin for adults is 500 Ојg / day IV for a maximum of 5-7 days, for children 15 Ојg / kg or 400 Ојg / m 2 / day, respectively.
The drug AknomidВ® is administered iv in the form of a 0.05% solution of rheopolyglucin. It can be added to infusion solutions: 5% dextrose solution or 0.9% sodium chloride solution.
The preparation of Acnomide D В® can also be applied by the method of isolated perfusion. The advantage of the method is the minimal drug exposure to other regions through systemic blood flow and prolonged effects on the tumor. The dose of the drug can be significantly higher than the dose used in the systemic route of administration, with the danger of toxic effects usually being less. The average dose is 50 Ојg / kg for the lower extremities and pelvic organs and 35 Ојg / kg for the upper extremities. Patients with obesity, as well as in cases of prior treatment with chemotherapeutic drugs and radiation, are recommended to prescribe smaller doses of the drug.
Toxic reactions to dactinomycin are frequent and can be severe. Excluding nausea and vomiting, they usually do not show up 2-4 days after the end of the course of therapy and may not be as pronounced within 1-2 weeks.
From the hemopoietic system: anemia (up to aplastic anemia), agranulocytosis, leukopenia, thrombocytopenia, pancytopenia, reticulocytopenia.
On the part of the digestive system: cheilitis, esophagitis, ulcerative stomatitis, pharyngitis, anorexia, nausea, vomiting, dysphagia, abdominal pain, diarrhea, gastrointestinal ulcers, proctitis.
From the hepatobiliary system: toxic liver damage (with possible development of hepatitis), jaundice, cholestasis, elevation of liver enzymes (most often associated with cholestasis), hepatic insufficiency.
From the skin and subcutaneous tissue: alopecia, rash, acne, relapse of erythema or increased pigmentation of skin areas that were previously exposed to radiation;Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme. There are reports of epidermolysis, erythema and edema, sometimes quite pronounced, arising from regional limb perfusion.
On the part of the respiratory system: pneumonia, interstitial lung disease, especially with long-term treatment.
Vascular disorders: primary thrombosis of hepatic veins, obliterating endophlebitis of hepatic veins.
From the side of metabolism: growth retardation.
On the part of the immune system: an increased risk of developing secondary infectious diseases, sepsis (including neutropenic sepsis).
Common reactions: malaise, fatigue, lethargy, drowsiness, fever, muscle pain, hypocalcemia.
- chicken pox, shingles caused by Herpes zoster (a severe generalized disease can develop which can result in death);
- oppression of bone marrow function, pronounced cytopenic reaction in drug or radiation therapy (in anamnesis);
- pronounced violations of the liver function;
- liver failure;
- the period of breastfeeding;
- Children's age up to 6 months;
- Individual intolerance (including history of hypersensitivity) of dactinomycin or components of the preparation AknomidВ®.
PREGNANCY AND LACTATION
The use of the drug is contraindicated in pregnancy and lactation.
Women and men of childbearing age during treatment and within 3 months after the end of therapy with the drug Aknomid В® should use reliable methods of contraception.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in severe violations of liver function
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in liver failure
APPLICATION FOR CHILDREN
Contraindicated in children up to 6 months.
The drug Aknomid D В® should be used only under the close supervision of a physician with experience in the use of antitumor chemotherapeutic drugs.
Symptoms of nausea and vomiting that develop during the first hours after drug administration can be stopped with antiemetic medications.
Against the backdrop of the use of the drug Aknomid D В® , the results of biological samples used to determine the effectiveness of antibacterial drugs may be distorted.
When conducting joint radiation therapy, the risk of toxic reactions from the gastrointestinal tract and bone marrow depression increases.
With special care, the drug is prescribed during a two-month therapy with a right-sided Wilms tumor, with hepatomegaly and an increase in hepatic transaminase activity.
The drug Aknomid D В® enhances the effect of radiation therapy.
Preparation of the solution, due to high toxicity, is recommended to be carried out in a cabinet with a biological protection class 2 with laminar flow; personnel performing its preparation should wear surgical gloves and a closed (surgical) robe with tied cuffs.
In case of accidental contact with the eye, immediately flush with plenty of water, and then seek advice from an ophthalmologist; In case of contact with skin, wash contaminated surface with plenty of water for 15 minutes.
With the development of severe myelosuppression, therapy with AcnomidВ®, especially when used in combination with other antineoplastic drugs, should be discontinued until bone marrow function is restored, usually about 3 weeks.
Complications after the application of the perfusion technique are mainly related to the amount of the drug that has entered the systemic bloodstream and can be characterized by oppression of the hematopoietic function, the absorption of toxic decay products from the site of massive destruction of tumor tissue, increased susceptibility to infections, deterioration of wound healing and superficial ulceration of the gastric mucosa. Other adverse effects may include swelling of the involved limb, soft tissue damage in the perfusion zone and (possibly) venous thrombosis. There are reports of increased incidence of secondary malignancies, including leukemia, after the application of treatment regimens including dactinomycin, irrespective of the concomitant use of radiotherapy.
In the process of treatment with the drug Acnomide D В® it is necessary to conduct daily determination of the content of platelets and leukocytes. If there is a significant decrease in the number of platelets or white blood cells, the drug should be discontinued until bone marrow function is restored (usually it takes about 3 weeks). A systematic determination of the activity of hepatic enzymes, bilirubin, and a general analysis of urine are also shown.
Nausea and vomiting, caused by the use of the drug AknomidВ®, lead to the necessity of prescribing the drug with intermittent courses.
If you get the drug under the skin and into the tissue, you should stop the infusion, but leave the needle in place. Try to remove the needle through the needle; if necessary, administer the antidote (1.6 ml of a 25% solution of sodium thiosulfate with 3 ml of water for injection, or 4 ml of a 10% solution of sodium thiosulfate with 6 ml of water for injection + 1 ml (50 mg) of ascorbic acid). After the introduction of the antidote, the needle should be removed. The extremities should be elevated and a cold compress applied for 45 minutes.
The unused preparation should be discarded by first disinfection with 5% trisodium phosphate for 30 minutes.
Impact on the ability to drive vehicles and manage mechanisms
Since the drug Aknomid D В® is able to influence the central nervous system (fatigue, dizziness), during the period of treatment it is necessary to refrain from driving vehicles and from occupations with potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
Symptoms: nausea, vomiting, diarrhea, stomatitis, gastrointestinal ulcers, severe hematopoietic suppression, acute renal failure, possible fatal outcome.
Treatment: symptomatic and supportive therapy. It is recommended that the kidneys, liver and bone marrow function be monitored frequently.
Other antitumor drugs and radiation therapy potentiate the effect of dactinomycin.
With the simultaneous use of dactinomycin with drugs that have a myelotoxic effect, it is possible to intensify the toxic effect.
With the simultaneous use of dactinomycin with uricosuric agents, the risk of developing nephropathy is increased.
When combined with doxorubicin, cardiotoxic effects can be increased.
Dactinomycin weakens the immune response to the introduction of inactivated viral vaccines; against the background of therapy with the use of this drug should refrain from vaccination with live viral vaccines. In addition, the use of dactinomycin weakens the effect of vitamin K.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 10 В° C. Shelf life - 3 years.