DACTINOMYCIN
Chemistry - An antibiotic antineoplastic agent, dactinomycin (also known as actinomycin D)occurs as a bright red, crystalline powder. It is somewhat hygroscopic and soluble in water at 10°Cand slightly soluble at 37°C. The commercially available preparation is a yellow lyophilized mixtureof dactinomycin and mannitol.
DNA-dependent RNA synthesis. Dactinomycin forms a complex with DNA and interferes with
DNA's template activity. Dactinomycin also possesses immunosuppressing and somehypocalcemic activity.
Dactinomycin crosses the placenta, but it is unknown whether it enters maternal milk. The majorityof the drug is excreted unchanged in the bile and urine.
Dactinomycin is contraindicated in patients who are hypersensitive to it. It should be used withcaution in patients with preexisting bone marrow depression, hepatic dysfunction, or infection.
Dactinomycin has been demonstrated to be embryotoxic and teratogenic in rats, rabbits andhamsters at higher than clinically used dosages. It should be used during pregnancy only when thepotential benefits outweigh its risks. While it is unknown if dactinomycin enters maternal milk, thepotential mutagenicity and carcinogenicity of the drug warrants using extreme caution in allowingthe mother to continue nursing while receiving dactinomycin.
Because dactinomycin can cause extensive pain and tissue damage, avoid extravasation injuries.
Dilution and administration by IV infusion is recommended or to administer slowly into a running IV line; use the "two-needle" technique.
There is increasing evidence that chronic exposure by health care-givers to antineoplastic drugsincreases the mutagenic, teratogenic and carcinogenic risks associated with these agents. Properprecautions in the handing, preparation, administration and disposal of these drugs and suppliesassociated with their use is strongly recommended.
Laboratory Considerations - Dactinomycin may interfere with determination of antibacterialdrug levels if using bioassay techniques.
Storage, Stability, Compatibility
The commercially available powder should be stored at roomtemperature and protected from light. When reconstituting, sterile water for injection withoutpreservatives must be used as preservatives may cause precipitation. After reconstituting, themanufacturer recommends using the solution immediately and discarding any unused portion as thesolution does not contain any preservatives. The reconstituted solution may be added to D5W ornormal saline IV infusions. IV fluid sterilizing filters (cellulose ester membrane) may partiallyremove dactinomycin.Pharmacology - DACTINOMYCIN
Dactinomycin is an antibiotic antineoplastic. While it has activity against grampositive bacteria, the drug's toxicity precludes its use for this purpose. Dactinomycin's exactmechanism of action for its antineoplastic activity has not been determined, but it apparently inhibitsDNA-dependent RNA synthesis. Dactinomycin forms a complex with DNA and interferes with
DNA's template activity. Dactinomycin also possesses immunosuppressing and somehypocalcemic activity.
Uses, Indications
Dactinomycin has been used as adjunctive treatment of lymphoreticular neoplasms, bone and soft tissue sarcomas, and malignant melanomas in small animals.Pharmacokinetics - DACTINOMYCIN
Because dactinomycin is poorly absorbed it must be given IV. It is rapidlydistributed and high concentrations may be found in bone marrow and nucleated cells.Dactinomycin crosses the placenta, but it is unknown whether it enters maternal milk. The majorityof the drug is excreted unchanged in the bile and urine.
Contraindications, Precautions, Reproductive Safety
Dactinomycin can cause life-threateningtoxicity. It should only be used where adequate monitoring and support can be administered.Dactinomycin is contraindicated in patients who are hypersensitive to it. It should be used withcaution in patients with preexisting bone marrow depression, hepatic dysfunction, or infection.
Dactinomycin has been demonstrated to be embryotoxic and teratogenic in rats, rabbits andhamsters at higher than clinically used dosages. It should be used during pregnancy only when thepotential benefits outweigh its risks. While it is unknown if dactinomycin enters maternal milk, thepotential mutagenicity and carcinogenicity of the drug warrants using extreme caution in allowingthe mother to continue nursing while receiving dactinomycin.
Adverse Effects, Warnings
Adverse effects that may be seen more frequently include anemia, leukopenia, thrombocytopenia (or other signs of bone marrow depression), ulcerative stomatitis orother GI ulceration. Because dactinomycin may cause increased serum uric acid levels, allopurinolmay be required to prevent urate stone formation in susceptible patients. Hepatotoxicity ispotentially possible with this agent.Because dactinomycin can cause extensive pain and tissue damage, avoid extravasation injuries.
Dilution and administration by IV infusion is recommended or to administer slowly into a running IV line; use the "two-needle" technique.
There is increasing evidence that chronic exposure by health care-givers to antineoplastic drugsincreases the mutagenic, teratogenic and carcinogenic risks associated with these agents. Properprecautions in the handing, preparation, administration and disposal of these drugs and suppliesassociated with their use is strongly recommended.
Overdosage, Acute Toxicity
Because of the toxic potential of this agent, iatrogenic overdosesmust be avoided. Recheck dosage calculations. See Adverse Effects above for additional information on toxicity.Drug Interactions
Other bone marrow depressant drugs (e.g., other neoplastics, chloramphenicol, flucytosine, amphotericin B or colchicine) may cause additive myelosuppression when used with dactinomycin. Additive cardiotoxicity may occur if used concurrently or sequentially with doxorubicin. Patients requiring vitamin K, may require higher dosages when receiving dactinomycin.Laboratory Considerations - Dactinomycin may interfere with determination of antibacterialdrug levels if using bioassay techniques.