Aknomid® (Aknomid D®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceDactinomycinDactinomycin
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  • Aknomid®
    solution in / in d / perfusion 
    Adikom, Open Company     Russia
  • Dactinomycin
    lyophilizate in / in d / perfusion 
    OMUTNINSK SCIENTIFIC EXPERIMENTAL-INDUSTRIAL BASE, OJSC     Russia
  • Cosmogen®
    lyophilizate for injections 
    Orphan Europe     France
    • Dosage form: & nbsp

    Solution for intravenous administration and perfusion.

    Composition:

    1 ml of the solution contains:
    active substance - dactinomycin - 0.5 mg, auxiliary agent -reopoliglyukin, solution for infusions (10% dextran solution, molecular weight from 3000 to 4000, in isotonic sodium chloride solution) - up to 1 ml.

    Description:

    Transparent liquid of golden color.

    Pharmacotherapeutic group:Antitumor agent, antibiotic
    ATX: & nbsp

    L.01.D.A.01   Dactinomycin

    L.01.D.A   Actinomycins

    Pharmacodynamics:

    Pharmacological action of dactinomycin is predominantly antitumoral, however, in addition, the drug has antibacterial, 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. Wherein dactinomycin intercalates between pairs of nitrogenous bases of guanine-cytosine DNA and interferes with the movement of RNA polymerase, thereby 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) is not used as an antimicrobial agent. Besides, dactinomycin has immunosuppressive activity.

    Pharmacokinetics:

    With intravenous administration, the drug accumulates in nuclear cells, penetrates insignificantly through the blood-brain barrier (<10%); penetrates the placenta. Much associated with tissue proteins. Metabolized poorly. The half-life is 36 hours. It is excreted with bile - 50% unchanged, kidneys - 10% unchanged. With bolus intravenous infusions of dactinomycin in adults at doses of 0.7 to 1.5 mg / m2 - the maximum concentration of the drug in an amount of 25.1 ng / ml is noted 15 minutes after the administration. The average concentration of dactinomycin after 6 hours is 2.67 mg / l.min.

    Indications:

    Neuroblastoma (Wilms Tumor); Rhabdomyosarcoma; Ewing's sarcoma; Neseminomnye malignant testicular tumors; Trophoblastic tumors; Locally recurrent or locally advanced solid tumors; in combination with radiotherapy;

    - in the preoperative and postoperative periods.

    Contraindications:

    - Individual intolerance (including hypersensitivity in anamnesis) of dactinomycin or components of the drug Aknomid®;

    - Chicken pox, shingles (herpes zoster, 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 history);

    - expressed violations of the liver, hepatic insufficiency;

    - hyperuricemia;

    - pregnancy, breast-feeding;

    - children age up to 6 months.

    Carefully:in patients older than 65 years (increased risk of myelosuppression); with gout or renal calculi (urate nephrolithiasis) in history (risk of hyperuricemia); with prior cytotoxic or radiotherapy; after chemotherapy or radiation therapy, simultaneous reception with live viral vaccines.
    Pregnancy and lactation:


    Dosing and Administration:

    Intravenously.

    Intravenous infusion administration of the drug Acnomide D® should be performed only in a hospital setting.

    The dose of Acnomid D® is selected individually, depending on the patient's tolerability, 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 / m2 within 5-7days. Usually, the adult dose is 500 mcg per 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 per day. IV for 5 days. There is an alternative course - a total dose of 2500 mcg / m2 in / in a 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 μg / kg per day for 5 days intravenously in combination with other chemotherapeutic agents in various treatment regimens, and the drug is administered at a dose of 45 μg / kg intravenously for Wilms tumor; in a dose of 1.25 mg / m2 intravenously struino for 3-5 minutes on the first dayevery 42 days the drug is prescribed with Ewing's sarcoma; for non-seminiferous malignant ovarian tumors, the recommended dose is 1000 μg / m2 intravenously on the first day of treatment in combination with cyclophosphamide, bleomycin, vinblastine and cisplatin; in trophoblastic tumors, the recommended dose is 12 μg / kg per day for 5 days as monotherapy and at a dose of 500 μg intravenously for 1.2 days as a combined regimen with etoposide, methotrexate, calcium folinate, vincristine, cyclophosphamide and cisplatin. It is possible to use combined therapy with dactinomycin and vincristine together with surgical treatment and radiotherapy, while dactinomycin and vincristine is 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 consistently.

    With grovelike sarcoma dactinomycin prescribe at medium doses of 500 mcg per day for 5 days in combination with radiation therapy, which leads to a 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 appoint both together and separately in combination with a surgical intervention, or without it. With metastatic non-seminomatous carcinoma, the testicular dactinomycin used as monotherapy, appointing cycles of 500 mcg / day. 5 days in a row, every 6-8 weeks, within 4 months. and more.

    With nonmetastatic gestational trophoblastic neoplasia: dactinomycin in a dose of 500 mcg / day for 5-7 days are used in conjunction with methotrexate at 30 mg / m2 in / m 1 p / ned. before the normalization of the HGT titer; Intermittent courses of therapy continue to three negative results of the test for the presence of HCT, conducted 1 p / 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. within 7 days.

    In locally recurrent or locally advanced solid tumors in combination with radiotherapy, the usual course dose of dactinomycin for adults is 500 mcg / day for a maximum of 5-7 days, for children 15 mcg / kg or 400 mcg / m2/ day, respectively.

    - The drug Aknomid D ® is administered intravenously in the form of 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 ® 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.

    Medium doses: 50 mcg / kg for lower extremities and pelvic organs; 35 μg / kg for 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.

    Side effects:

    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.

    General disorders: malaise, fatigue, lethargy, drowsiness, fever, muscle pain, hypocalcemia.

    Violations from the blood system and lymphatic system: anemia (up to aplastic anemia), agranulocytosis, leukopenia, thrombocytopenia, pancytopenia, reticulocytopenia.

    Gastrointestinal disorders: cheilitis, esophagitis, ulcerative stomatitis, pharyngitis, anorexia, nausea, vomiting, dysphagia, abdominal pain, diarrhea, gastrointestinal ulcers, proctitis.

    Disorders of the hepatobiliary system: toxic liver damage (with possible development of hepatitis), jaundice, cholestasis, elevation of liver enzymes (most often associated with cholestasis), hepatic insufficiency.Changes in 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. Disturbances from the respiratory system, chest and mediastinal organs: pneumonitis, interstitial lung disease, especially with long-term treatment.

    Vascular disorders: primary thrombosis of hepatic veins, obliterating endophlebitis of hepatic veins.

    Metabolic disorders, growth retardation.

    Immune system disorders: increased risk of developing secondary infectious diseases, sepsis (including neutropenic sepsis).

    Overdose:

    Symptoms are: nausea, vomiting, diarrhea, stomatitis, gastrointestinal ulcers, severe hematopoietic suppression, acute renal failure, a possible fatal outcome. Treatment: symptomatic and supportive. It is recommended that the kidneys, liver and bone marrow function be monitored frequently.

    Interaction:

    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.

    Special instructions:

    The drug Aknomid D® 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 treated with antiemetic medications; distorts the results of biological samples,used to determine the effectiveness of antibacterial drugs; when joint radiation therapy is used, 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 right-sided Wilms tumor, with hepatomegaly and an increase in the activity of "liver" transaminases; 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 pronounced myelosuppression, therapy with Acnomid D®, especially in those cases,when it is used in combination with other antitumor drugs, should be discontinued before the restoration of bone marrow function, usually it takes about three 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 malignant neoplasms, including leukemia, after the application of treatment regimens including dactinomycin, irrespective of the simultaneous appointment of radiotherapy; women and men during treatment and within 3 months after the end of therapy with the drug Aknomid® should use reliable methods of contraception.In the process of treatment with the drug Acnomide D ®, daily platelet and leukocyte counts must be determined. 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 Aknomid®, lead to the necessity of prescribing the drug with intermittent courses.

    If the product gets under the skin and into the tissue, the infusion should be interrupted, 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 / 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.

    Unused preparation should be discarded by first disinfection with 5% -trisodium phosphate for 30 minutes.

    Effect on the ability to drive transp. cf. and fur:

    Because the drug Aknomid D® is able to influence the central nervous system (fatigue, dizziness) during the period of treatment should refrain from driving motor vehicles and from activities potentially hazardous activities that require high concentration and psychomotor speed reactions.

    Form release / dosage:

    A solution for intravenous perfusion, and 0.5 mg / ml, 1 ml solution into dark glass ampoules, 5 vials in a plastic pencil case, 1 canisters along with instructions for medical use in a cardboard package.

    Storage conditions:

    Store at a temperature not exceeding 10 ° C. Keep out of the reach of children.

    Shelf life:

    3 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002036
    Date of registration:01.04.2013
    Expiration Date:01.04.2018
    The owner of the registration certificate:Adikom, Open CompanyAdikom, Open Company Russia
    Manufacturer: & nbsp
    Information update date: & nbsp21.09.2016
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