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Powder for solution for injection containing 500micrograms dactinomycin per vial
When reconstituted as directed, the solution will contain 500micrograms/ml

Drugs List

  • COSMEGEN LYOVAC 500microgram powder for solution for injection
  • dactinomycin 500microgram powder for solution for injection
  • Therapeutic Indications


    As combination chemotherapy and/or multi-modality treatment for:
    Wilms' tumour
    Childhood rhabdomyosarcoma
    Ewing's sarcoma
    Metastatic nonseminomatous testicular cancer

    As a single agent or as part of a combination chemotherapy regimen for the treatment of gestational trophoblastic neoplasia

    As combination therapy with melphalan for the treatment of locally recurrent or loco regionally metastatic melanoma


    Treatment with dactinomycin should only be performed under the direct supervision of a physician experienced in oncological practices.

    Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

    Toxic reactions to dactinomycin are frequent and the severity of such reactions may be dose limiting. However, the severity of toxicity varies greatly and is only partly dependant on the dosage.

    The dosage used will depend on the tolerance of the patient, the size and location of the neoplasm and the use of other forms of therapy. It may be necessary to reduce the recommended doses when additional chemotherapy or radiation is used concurrently or has been used previously.

    Dosage is calculated in micrograms. The dose intensity per 2 week cycle for adults and children should not exceed 15 micrograms/kg/day or 400-600micrograms/metre squared body surface area daily, intravenously, for 5 days.


    Wilm's tumour, rhabdomyosarcoma and Ewing's sarcoma:
    15micrograms/kg intravenously, daily, for 5 days.

    Testicular carcinoma:
    1,000micrograms/metre squared intravenously on day 1 as part of a combination regimen with cyclophosphamide, bleomycin, vinblastine and cisplatin.

    Gestational trophoblastic neoplasia:
    12micrograms/kg intravenously daily for 5 days as a single agent.
    Or alternatively:
    500micrograms intravenously on days 1 and 2 as part of a combination regimen with etoposide, methotrexate, folinic acid, vincristine, cyclophosphamide and cisplatin.

    Regional perfusion in locally recurrent and loco regionally metastatic melanoma:
    The dosage schedules and the technique itself vary. Published literature should be consulted for further details.

    In general the following dosage regimens are recommended:
    For a lower extremity or pelvis - 50micrograms/kg
    For an upper extremity - 35micrograms/kg


    See Dosage; Adults.


    Children over 12 months of age:
    See Dosage; Adults.

    Under 12 months of age:
    Dactinomycin should not be given to children under the age of 12 months unless the potential benefits outweigh the risks.

    There is a greater frequency of toxic effects in infants.

    Additional Dosage Information

    Calculations of the dosage for obese or oedematous patients should be on the basis of surface area in an effort to relate dosage to lean body mass. It may be advisable to use lower doses in obese patients, or when previous chemotherapy or radiotherapy has been employed.


    For administration by intravenous injection or infusion.

    If dactinomycin is injected directly into the vein as an injection, the 'two needle' technique should be used. One needle to draw the solution from the vial and one needle to inject the solution.


    Standard guidelines on handling cytotoxic drugs should be followed:
    1. Trained personnel should reconstitute cytotoxics;
    2. Reconstitution should be carried out in designated areas;
    3. Protective clothing (including gloves) should be worn;
    4. The eyes should be protected and means of first aid should be specified;
    5. Pregnant staff should not handle cytotoxics;
    6. Adequate care should be taken for the disposal of waste material, including syringes, containers and absorbent material.

    Inhalation of dust or vapours, contact with the skin, mucous membranes and the eyes should be avoided.

    Should accidental contact with the eyes occur: Irrigate the eyes with water, normal saline or a balanced salt ophthalmic irrigating solution for at least 15 minutes. Prompt ophthalmic consultation should follow.

    Should accidental skin contact occur: Washed the affected area with plenty of water for at least 15 minutes. Medical attention should be sought immediately.


    Dactinomycin should be reconstituted by adding 1.1ml of water for injections to the vial.
    For injection, 1.0ml of the solution should be withdrawn from the vial. (1ml of the solution will contain 500micrograms dactinomycin).

    The solution should be inspected for particulate matter and discolouration prior to use. The reconstituted solution is clear and gold coloured.

    When reconstituted, dactinomycin solution can be added to an infusion solution of 5% dextrose injection or sodium chloride injection, either directly or into the tubing of a running intravenous infusion.

    Reconstituted dactinomycin is chemically stable, however the product does not contain any preservative and any unused portion of the solution should be discarded.


    Water containing preservatives (benzyl alcohol or parabens) to reconstitute dactinomycin for injections results in the formation of a precipitate.

    Partial removal of dactinomycin from intravenous solutions by cellulose ester membrane filters used in some intravenous in-line filters has been reported.

    Precautions and Warnings

    Treatment should only be administered under the supervision of a physician experienced in the use of chemotherapeutic agents.

    Whilst the doses stated are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

    If dactinomycin is given at or about the same time as infection with varicella or herpes zoster, a severe generalised disease, which may be fatal can occur.

    Upon intravenous administration of dactinomycin extravasation may occur with or without being accompanied by a burning or stinging sensation, even if blood returns well on aspiration of the infusion needle. If there is evidence that extravasation has occurred, the injection or infusion should be terminated and restarted in another vein. Intermittent application of ice to the site of extravasation, for 15 minutes 4 times daily for 3 days may be useful. Due to the progressive nature of extravasation reactions, close observation and a consideration to plastic surgery is recommended.

    Renal, hepatic and bone marrow functions should be assessed frequently as a variety of functional abnormalities has been reported. Platelet and white blood cell counts should be performed frequently to detect severe hematopoietic depression. If either count shows a marked decrease, dactinomycin should be withheld to allow marrow recovery. This often takes up to three weeks.

    Patients should be carefully and regularly observed for any toxic adverse reactions. The possibility of anaphylactoid reactions should be considered. It is especially important to observe the patient daily for toxic reactions when dactinomycin is used in combination therapy. Occasionally a full course of treatment will not be tolerated.

    If stomatitis, diarrhoea or severe haematopoietic suppression occur, treatment should be withdrawn until the patient recovers. Advise patients to report any signs of diarrhoea and stomatitis.

    Veno-occlusive disease (primarily hepatic) has been reported in patients receiving dactinomycin as part of a multidrug chemotherapy regimen and may result in fatality, particularly in children younger than 48 months.

    As with other antineoplastic agents, dactinomycin may have effects on fertility.

    The ability to drive or operate machinery may be affected by side effects e.g. lethargy and fatigue.

    There has been an increased incidence of gastrointestinal toxicity and marrow suppression when dactinomycin is used in combination with radiation therapy. Normal skin as well as the buccal and pharyngeal mucosa may show early erythema. A reduced dose of radiation administered in combination with dactinomycin causes erythema and vesiculation, which progresses more rapidly through the stages of tanning and desquamation. Healing may occur in 4 to 6 weeks. Erythema from previous radiotherapy may be reactivated by dactinomycin alone, even if the radiation was administered many months previously but especially if the interval between the two types of therapy is brief. Such potentiation of radiation effect is especially problematic when the radiotherapy involves the mucous membranes. When radiation is directed towards the nasopharynx, severe oropharyngeal mucositis may occur. If the patient is especially sensitive to such combination therapy, or high doses are used, severe reactions may occur.

    When treating Wilm's tumour, dactinomycin should not be used in combination with radiation unless the expected benefits outweigh the risks. Caution is needed when administering dactinomycin within two months of irradiation for the treatment of right-sided Wilm's tumour since hepatomegaly and elevated AST levels have been reported.

    An increased incidence of secondary primary tumours, including leukaemia, following radiotherapy in combination with antineoplastic agents such as dactinomycin has been reported.

    Pregnancy and Lactation


    Dactinomycin is contraindicated during pregnancy.

    Limited data are available, at the time of writing, on the use of dactinomycin during human pregnancy. Although, dactinomycin has been shown to be mutagenic in vitro and in vivo in human tissues.

    Dactinomycin has been shown to be teratogenic and embryotoxic in rats, rabbits and hamsters.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Dactinomycin is contraindicated during breastfeeding.

    The high molecular weight should limit the amount of dactinomycin excreted into milk. However due to the potential risk on the nursing infant of severe adverse reactions, dactinomycin should not be given to breastfeeding women. Schaefer recommends withholding from breastfeeding for at least 7 days following treatment with dactinomycin.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at


    Advise patients dactinomycin may have effects on fertility.

    Advise patients to report any signs of diarrhoea and stomatitis.

    Advise patients their ability to drive and operate machinery may be impaired by some side effects associated with dactinomycin.

    Side Effects

    Renal disorders
    Growth retardation (children)
    Ulcerative stomatitis
    Abdominal pain
    Gastro-intestinal ulceration
    Liver toxicity
    Liver function disturbances
    Hepatic veno-occlusive disease
    Aplastic anaemia
    Skin eruption
    Hyperpigmentation of skin
    Impaired healing
    Gastric ulceration
    Venous thrombosis
    Tissue damage(injection site)
    Hepatic failure
    Febrile neutropenia
    Increased susceptibility to infection
    Bone marrow depression


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Shelf Life and Storage

    Store below 25 degrees C
    Store in the outer carton to protect from light
    Do not freeze

    Reference Sources

    BNF for Children (2011-2012) Pharmaceutical Press, London.

    British National Formulary, 62nd Edition (2011) Pharmaceutical Press, London.

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

    Summary of Product Characteristics: Cosmegen Lyovac. Lundbeck. April 2011.
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