Cosmogen® (Cosmegen)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceDactinomycinDactinomycin
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    Orphan Europe     France
    • Dosage form: & nbsplyophilized powder for injection
    Composition:

    1 bottle contains:

    active substance: dactinomycin 0.55 mg;

    Excipients: mannitol 22.0 mg (equivalent to the content of dactinomycin 0.5 mg / ml, mannitol 20.0 mg / ml).

    Description:Lyophilized powder from yellow to orange.
    Pharmacotherapeutic group:Antitumor agent, antibiotic
    ATX: & nbsp

    L.01.D.A.01   Dactinomycin

    L.01.D.A   Actinomycins

    Pharmacodynamics:

    Dactinomycin is one of the representatives of the class of actinomycins, a group of antibiotics produced by various species Streptomyces. Dactinomycin is the main component of a mixture of actinomycins produced Streptomyces parvullus.

    The action of dactinomycin is based on the formation of complexes with DNA and the selective inhibition of DNA-dependent RNA synthesis. It is believed that dactinomycin inhibits protein synthesis by inhibiting the synthesis of matrix RNA. Dactinomycin inhibits the synthesis of DNA, but at much higher concentrations than necessary to inhibit the synthesis of RNA.
    Pharmacokinetics:

    After intravenous administration dactinomycin quickly distributed and enters virtually all tissues of the body. Metabolism is minimal, penetrating insignificantly through the blood-brain barrier (<10%). The concentration of the drug in the plasma rapidly decreases within 2 hours, after which the intensity of the decrease in concentration slows down; the half-life is approximately 36 hours. In case of violations of the liver function, the half-life period may increase. Approximately 30% of the administered dose is excreted in urine and feces unchanged for one week.

    Indications:

    - Wilms tumor.

    - Rhabdomyosarcoma.

    - Ewing's sarcoma.

    - Neseminomnye malignant tumors of the testicle.

    - Gestational trophoblastic tumors.

    - Locally recurrent or locally advanced solid tumors.

    Contraindications:

    - Hypersensitivity to dactinomycin or any other component of the drug.

    - Chicken pox or shingles.

    - Children up to 6 months.

    - Breastfeeding period.

    Carefully:Patients over 65 years of age (due to an increased risk of myelosuppression); after chemotherapy or radiation therapy; simultaneous reception with live viral vaccines; pregnancy.
    Pregnancy and lactation:

    Adequate and controlled clinical trials of drug use in pregnant women have not been conducted. Cosmogen® should be given to pregnant women only if the potential benefit of treatment exceeds the potential risk to the fetus. On the background of Cosmagenom therapy, reliable contraceptive methods should be used: women who have fertility potential should be warned about the unwantedness of pregnancy on the background of therapy. If Cosmegen® is used against the background of pregnancy, or if the pregnancy has occurred while taking the drug, the patient should be informed of the potential harm to the fetus.

    It is not known whether the drug is excreted in breast milk. Since many drugs are excreted in breast milk, and because of possible serious side effects of Cosmegen® in children, the drug is contraindicated in breastfeeding.

    Dosing and Administration:

    Only for parenteral use

    It is necessary to carefully calculate each dose before administration.

    Intravenous administration

    The dosage regimen is set individually, depending on the tolerability of the drug, the size and location of the tumor, as well as the use of other types of treatment.With simultaneous or previously conducted radiation or chemotherapy, there may be a need to reduce the commonly used doses of the drug given below. The dose rate for a 2-week course for adults and children should not exceed 15 μg / kg / day or 400-600 μg /m2 the surface of the body per day intravenously for 5 days.

    When calculating the required dose per kg of body weight for patients suffering from obesity or edema, the body surface area should be taken into account so that the result correlates with dosages for patients with normal body weight.

    WILMS TUMOR

    Assign 45 μg / kg Cosmegen ® intravenously in combination with other chemotherapeutic agents in various treatment regimens.

    RABDOMIOSARCOM

    The recommended regimen is 15 mcg / kg per day intravenously for five days in combination with other chemotherapeutic agents in various treatment regimens.

    SARCOM Ewing

    Assign 1.25 mg / m2 surface of the body intravenously in combination with other chemotherapeutic agents in various treatment regimens.

    NON-MEMORY MALIGNANT TUMOR TUMORS

    1000 mcg / m intravenously on the first day of treatment in combination with cyclophosphamide, bleomycin, vinblastine and cisplatin.

    GESTATION TROPHOBLASTIC TUMORS

    12 mcg / kg / day intravenously for 5 days as a monotherapy. 500 μg intravenously on days 1 and 2, as a component of the combined regimen with etoposide, methotrexate, calcium folinate, vincristine, cyclophosphamide and cisplatin.

    Regional perfusion

    REGIONAL PERFUSION IN LOCAL-RECURRENT OR LOCALLY DISTRIBUTED SOLID TUMORS

    - 50 μg / kg (0.05 mg) of body weight when the tumor is localized in the region of the lower extremities or pelvic region.

    - 35 μg / kg (0.035 mg) of body weight when the tumor is localized in the region of the upper limbs.

    Usually, with the administration of a dose of the drug elderly patients care should be taken and the lowest doses should be given first, bearing in mind that this group of patients is more likely to have decreased liver, kidney or heart function, and also considering the presence of possible co-morbidities or treatment with other drugs.

    Cosmegen® is not subject to significant elimination through the kidneys, so if the renal dysfunction is not corrected Cosmegen® dosage is not required.

    Mode of application

    Cosmogen® dissolve in 1.1 ml of sterile water for injection (without preservatives), observing aseptic precautions.The resulting solution contains approximately 500 μg (0.5 mg) of dactinomycin in 1 ml. Before application of drugs, intended for parenteral administration, must be visually verified on subject of detection foreign particles and color changes, if solution and packaging permit this. After breeding Cosmegen® is a clear solution of golden color.

    Immediately after dilution, a solution of dactinomycin can be added to infusion solutions of 5% dextrose or 0.9% sodium chloride solution, either directly or into the dropper tube during intravenous administration.

    Diluted dactinomycin remains a chemically stable solution, but the preparation does not contain preservatives, which can lead to the accidental ingestion of microorganisms into the solution.

    The unused amount of the prepared solution must be disposed of. The use of water containing preservatives (gasoline alcohol or parabens) to dilute Cosmegen® leads to the formation of a sediment.

    There are reports of partial removal of Cosmegen® from intravenous solutions by filtration through membranes from cellulose ethers used in some intravenous solutions with built-in filters.

    When you administer the drug directly into the vein without an infusion solution, you should use a "two-needle" method. One sterile needle is used to dilute the drug and extract the calculated dose from the vial. Another sterile needle is used to directly inject the drug into a vein.

    Side effects:

    When Cosmegen® is used, toxic reactions often develop, which can be severe, which in many cases limits the prescribed doses of the drug. However, the severity of toxic lesions can be different and only partially depends on the dose of the drug.

    Toxic effects (with the exception of nausea and vomiting) usually appear after two to four days after stopping the course of therapy and reach maximum severity after one or two weeks. There are reports of lethal cases. However, usually side effects are reversible and disappear after discontinuation of therapy. Side effects include:

    From the side of the blood and lymphatic system: anemia, up to aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, pancytopenia, reticulocytopenia, neutropenia, febrile neutropenia.

    On the part of the respiratory system, the organs of the thorax and the mediastinum: pneumonitis.

    From the gastrointestinal tract: anorexia, nausea, vomiting, abdominal pain, diarrhea, ulcerative lesions of the gastrointestinal tract, cheilitis, dysphagia, esophagitis, ulcerative stomatitis, pharyngitis.

    From the liver and bile ducts: toxic liver damage, including changes in functional liver samples, ascites, hepatomegaly, hepatitis, hepatic insufficiency with a fatal outcome, primary thrombosis of hepatic veins, obliterating endophlebitis of hepatic veins.

    From the skin and skin appendages: alopecia, skin rash, acne, erythema multiforme, recurrence of erythema, or increased pigmentation of skin areas previously exposed to radiation. In the post-registration period, cases of toxic epidermal necrolysis and Stevens-Johnson syndrome were documented.

    Dactinomycin has an extremely high corrosive effect. If there is a bleeding during intravenous administration, this will lead to serious damage to the soft tissues. At least in one case this led to the development of Dupuytren's contracture. There are reports of epidermolysis, erythema and edema, sometimes quite pronounced, arising from regional limb perfusion.

    Laboratory data: there are reports of multiple violations from the kidneys, liver and bone marrow in patients with malignant tumors receiving Cosmogen ® treatment. It is recommended that a frequent examination of the liver, kidneys and bone marrow.

    Other: sepsis (including neutropenic sepsis) fatal, malaise, fatigue, lethargic sleep, fever, myalgia, proctitis, growth retardation and infectious diseases, hypocalcemia.

    Overdose:

    Manifestations of an overdose include nausea, vomiting, diarrhea, mucositis (including stomatitis, gastrointestinal ulceration), acute skin damage (including peeling, exanthema, desquamation and epidermolysis), severe hematopoietic suppression, primary vein thrombosis, acute renal failure, sepsis (including neutropenic sepsis) with a fatal outcome, as well as death. Specific information on the treatment of Cosmegen® overdose is not available. Treatment is symptomatic and supportive. It is recommended to carry out a regular investigation of the integrity of the skin and mucous membranes, as well as the kidneys, liver and bone marrow function.

    Interaction:

    With the simultaneous use of Cosmegen® and radiation therapy, toxic effects on the part of the gastrointestinal tract and hematopoiesis are enhanced.

    With simultaneous administration with live viral vaccines, it is possible to intensify the process of replication of the vaccine virus, increase its side / adverse effects and / or reduce the production of antibodies in the patient's body in response to the introduction of the vaccine.

    Special instructions:

    Cosmogen® should only be used under close supervision of a physician with experience in the use of antitumor chemotherapeutic drugs.

    Nausea and vomiting that occur within the first few hours after taking the drug can be alleviated with antiemetic drugs.

    Against the backdrop of Cosmegen® therapy, it is necessary to regularly determine the number of platelets and white blood cells in the blood in order to detect a pronounced inhibition of hematopoietic function, as well as to regularly examine the function of the kidneys and liver.

    With the development of severe myelosuppression, Cosmogen® therapy, especially when used in combination with other antitumor drugs, should be discontinued until bone marrow function is restored.Usually it takes about three weeks.

    When Cosmegen® is administered, extravasation should be carefully avoided. When the first signs of extravasation appear (burning or soreness at the injection site or other signs), the administration of Cosmegen® should be stopped immediately; the rest of the drug should be injected into another vein. On the extravasation area it is recommended to apply ice for 15 minutes 4 times a day for 3 days. Careful observation is recommended for the patient. In the event of the appearance of blisters, ulcers and / or constant pain, it is necessary to discuss with a plastic surgeon the possibility of excision of a large area of ​​skin followed by a split skin flap transplant.

    Primary thrombosis of the veins (mainly the liver) can lead to death of the patient, especially children younger than 48 months.

    Cosmogen® and regional perfusion technique

    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 include 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 is evidence of an increase in the frequency of toxic reactions from the gastrointestinal tract and depression of bone marrow function in the appointment of a combination therapy including Cosmegen® and radiotherapy. In addition, on the normal skin, as well as on the mucous cheeks and pharynx, early signs of erythema can be detected. The use of smaller than usual doses of radiotherapy in combination with Cosmegen® causes the appearance of erythema and vesiculation, which progress more rapidly, passing through the stages of compaction and desquamation. The healing in this case can occur within four to six weeks instead of two to three months. Erythema resulting from previous radiation therapy may reappear under the influence of monotherapy with dactinomycin even when the irradiation was performed many months ago, and with greater probability, if the time interval between the two therapies was short. Such a potentiation of the effects of radiation therapy is of particular importance when the irradiation zone includes the mucosa.If irradiation is directed to the nasopharynx, then combined treatment can lead to severe inflammation of the mucous membrane of the oropharynx.

    Expressed reactions can occur in the case of concomitant administration of high doses of Cosmegen® and radiotherapy, as well as with increased sensitivity of the patient to such a combination therapy.

    Special care must be taken when using Cosmegen® during a two-month radiotherapy for treatment of the right-sided Wilms tumor, since there is evidence of hepatomegaly and an increase in the level ACT. It is not recommended to administer Cosmegen® concomitantly with radiotherapy for the treatment of Wilms' tumor, except when the benefit to the patient exceeds the possible risk.

    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 Cosmagen ® therapy should use reliable methods of contraception.

    When using the drug should be observed all the usual instructions adopted for the use of cytotoxic drugs. If it gets on the skin or mucous membranes, they should be washed immediately and thoroughly with water, physiological solution.

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

    Admission of this medication is associated with the occurrence of severe side effects that may affect the ability of some patients to drive and operate machinery.

    When taking Cosmegen®, it is recommended to refrain from driving the car and controlling complex mechanisms.

    Form release / dosage:

    Lyophilized powder for injection 0.5 mg.

    Packaging:

    For 0.5 mg (500 μg) of lyophilizate in bottles of dark glass.

    For 1 bottle together with instructions for medical use in cardboard pack.

    Storage conditions:

    Store in a dry, dark place at a temperature of no higher than 30 ° 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:П N012030 / 01
    Date of registration:27.07.2010 / 09.02.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:Orphan EuropeOrphan Europe France
    Manufacturer: & nbsp
    Representation: & nbspRUSFIK LLC RUSFIK LLC Russia
    Information update date: & nbsp05.02.2018
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