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dactinomycin

 
Dictionary: dac·ti·no·my·cin   (dăk'tə-nō-mī'sĭn) pronunciation
 
n.

An antibiotic of the actinomycin group, C62H86N12O16, isolated from bacteria and used as an antineoplastic agent in the treatment of certain cancers. Also called actinomycin D.

[D– + ACTINOMYCIN.]


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Oncology Encyclopedia: Dactinomycin
 

Key Terms: Antineoplastics, Cytotoxic, Ewing's sarcoma, Gestational trophoblastic cancer, Kaposi's sarcoma, Myeloma, Oncologist, Rhabdomyosarcoma.

Definition

Dactinomycin is a chemotherapeutic agent belonging to a family of medicines known as antineoplastic drugs. Alternative trade names or brand names for dactinomycin include Actinomycin-D and Cosmegen.

Description

Dactinomycin is one of the older chemotherapy drugs, having gained approval from the Food and Drug Administration (FDA) in 1982. This highly potent and effective cytotoxic agent is a mixture of substances produced by the bacteria Streptomyces parvullus. Its toxic properties prevent its use as an antibiotic.

Dactinomycin interferes with the growth of cancer cells by complexing with a cell's genetic material (deoxyribonucleic acid, or DNA). This prevents the cell from producing the proteins necessary to function and grow, thereby killing it. Dactinomycin may be used as a single chemotherapeutic agent or in conjunction with other antineoplastics (such as vincristine and cyclophosphamide) for greater efficacy.

Purpose

Dactinomycin is used in the treatment of Ewing's sarcoma, Wilms' tumor, rhabdomyosarcoma, gestational trophoblastic tumors, Kaposi's sarcoma, and soft tissue sarcomas. It is less commonly used for cancers of the uterus and testis.

Recommended Dosage

The exact schedule and method of dactinomycin administration will be prescribed by an oncologist based on the type and stage of the cancer. An appropriate starting treatment regimen for adult patients is 500 mg/day for five consecutive days at two to four week intervals if the drug is tolerated. For children the dose is 15 mg/day over the same time course as prescribed for adults. Dactinomycin is not recommended for children less than one year of age; little clinical data is available on the use of dactinomycin in the elderly. Administration may be by intravenous (IV) injection, through a running IV infusion, or through a central line inserted under the skin into a vein near the collarbone.

Precautions

To maximize treatment effects, patients receiving dactinomycin should observe the following guidelines, as well as any modifications given by the oncologist:

  • The area surrounding the injection site should be monitored.
  • Patients should have regular laboratory testing for white blood cell count and kidney, liver, and bone marrow function.
  • In order to reduce the possibility of immunosuppression, immunizations not approved or prescribed by the oncologist should be avoided.
  • Patients should avoid contact with individuals taking or that have recently taken the oral polio vaccine, or individuals that have an active infection. When necessary a protective facemask should be worn.
  • Oral hygiene procedures should be followed to reduce the risk of gum abrasion.
  • Patients should not touch eye and nasal areas unless hands have been properly washed immediately prior to contact.
  • To reduce bleeding and bruising complications, patients should exercise extreme caution when handling sharp instruments and decline participation in contact sports.
  • Prior to treatment, the patient's medical history should be thoroughly reviewed to avoid complications that might arise from previous conditions such as gout, kidney stones, liver disease, chickenpox, shingles, or a history of allergic reactions to various drugs.
  • The oncologist should be made aware if the patient is pregnant or if there is the possibility the patient might be pregnant, or if the patient is a breast-feeding mother.
  • Only prescribed medications or over the counter (OTC) drugs approved by the oncologist should be taken by a patient receiving dactinomycin.

Side Effects

Possible side effects of treatment with dactinomycin should be discussed with the patient prior to initiation of treatment. The patient should be instructed to notify the oncologist of any side effects. Side effects that may not be life threatening but give the patient cause for concern include hair loss (alopecia), intermittent diarrhea, nausea and vomiting, loss of appetite, difficulty swallowing, mouth sores or ulcers, and a general rash or change in skin tone. Side effects that should be reported immediately to the oncologist include unusual bleeding or bruising, black tarry stools, blood in the urine or stool, development of a cough, wheezing or hoarseness, fever or chills, lower back or side pain, painful or difficult urination, pinpoint red spots on the skin, and pain at the site of the injection. The oncologist will decide what type of intervention is best suited to control or extinguish the presented side effects, including changing the dosage, changing the treatment schedule, or discontinuing dactinomycin treatment.

Interactions

Certain medications should never be used together, but there are cases in which multiple drug treatment may be advisable even when drug interaction is well documented. Dactinomycin may be used in conjunction with other antineoplastic drugs or radiation therapy for increased efficacy of treatment. Under such conditions the oncologist will balance dosage and treatment schedules to maximize the positive effects of all drugs given and minimize any negative interactions.

It is essential that the oncologist be aware of any drugs that the patient is presently taking or has recently taken, or if the patient has recently received radiation therapy. A careful review of drugs that may interact with dactinomycin to lower its efficiency should be covered with the patient prior to treatment. These may include, but are not limited to, amphotericin B, antithyroid agents, azathioprine, chloramphenicol, flucytosine, ganciclovir, interferon, plicamycin, zidovudine, probenecid, and sulfinpyrazone.

—Jane Taylor-Jones, Research Associate, M.S.

 
Drug Info: Dactinomycin, Actinomycin D
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Brand names: Cosmegen®

Chemical formula:



Dactinomycin Solution for injection

What is this medicine?

DACTINOMYCIN is a chemotherapy drug. It is used to treat many kinds of cancer like Wilms' tumor, some sarcomas, and placental and testicular cancers. It is also used to treat other solid tumors.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•infection (especially a virus infection such as chickenpox, cold sores, or herpes)
•liver disease
•low blood counts like low platelets, red blood cells, white blood cells
•recent radiation therapy
•an unusual or allergic reaction to dactinomycin, other chemotherapy agents, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

This drug is given as an infusion into a vein. It is administered in a hospital or clinic by a specially trained health care professional.

Talk to your pediatrician regarding the use of this medicine in children. While this drug may be prescribed for children as young as 6 months of age for selected conditions, precautions do apply.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

•medicines to increase blood counts like filgrastim, pegfilgrastim, sargramostim
•vaccines

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Your condition will be monitored carefully while you are receiving this medicine. You will need important blood work done while you are taking this medicine.

This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.

Call your doctor or health care professional for advice if you get a fever, chills or sore throat, or other symptoms of a cold or flu. Do not treat yourself. This drug decreases your body's ability to fight infections. Try to avoid being around people who are sick.

This medicine may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding.

Be careful brushing and flossing your teeth or using a toothpick because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving this medicine.

Avoid taking products that contain aspirin, acetaminophen, ibuprofen, naproxen, or ketoprofen unless instructed by your doctor. These medicines may hide a fever.

Do not become pregnant while taking this medicine. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information. Do not breast-feed an infant while taking this medicine.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•low blood counts - this medicine may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding.
•signs of infection - fever or chills, cough, sore throat, pain or difficulty passing urine
•signs of decreased platelets or bleeding - bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine
•signs of decreased red blood cells - unusually weak or tired, fainting spells, lightheadedness
•breathing problems
•changes in vision
•chest pain
•mouth sores
•pain, swelling, redness at site where injected
•seizures
•stomach pain, ulcers
•swelling of the ankles, feet, hands, or stomach
•trouble passing urine or change in the amount of urine
•vomiting
•yellowing of the eyes or skin

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•acne-like skin rash
•darker skin color
•diarrhea
•hair loss
•loss of appetite
•nausea

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

This drug is given in a hospital or clinic and will not be stored at home.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

 
Veterinary Dictionary: dactinomycin
Top

An antibiotic of the actinomycin complex (actinomycin D), produced by several species of Streptomyces; used as an antineoplastic agent.

 
Wikipedia: Actinomycin
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Actinomycin D
Systematic (IUPAC) name
2-amino-N,N'- bis[(6S,9R,10S,13R,18aS)- 6,13-diisopropyl- 2,5,9-trimethyl- 1,4,7,11,14-pentaoxohexadecahydro- 1H-pyrrolo[2,1-i] [1,4,7,10,13] oxatetraazacyclohexadecin- 10-yl]- 4,6-dimethyl- 3-oxo- 3H-phenoxazine- 1,9-dicarboxamide
Identifiers
CAS number 50-76-0
ATC code L01DA01
PubChem 2019
DrugBank APRD00124
Chemical data
Formula C62H86N12O16 
Mol. mass 1255.42 g/mol
Synonyms 2-Amino- 4,6-dimethyl- 3-oxo- 3H-phenoxazine- 1,9-dicarboxylic acid bis- [(5,12-diisopropyl- 9,13,16-trimethyl- 4,7,11,14,17-pentaoxo- hexadecahydro- 10-oxa- 3a,6,13,16-tetraaza- cyclopentacyclohexadecen- 8-yl)- amide]
Pharmacokinetic data
Bioavailability  ?
Protein binding 5%
Metabolism  ?
Half life 36 hours
Excretion  ?
Therapeutic considerations
Pregnancy cat.

?

Legal status
Routes  ?

The actinomycins are a class of polypeptide antibiotics isolated from soil bacteria of the genus Streptomyces, of which the most significant is actinomycin D. It was the first antibiotic isolated by Selman Waksman and his co-worker H. B. Woodruff in 1940.[1]

General structure of actinomycins


Contents

Mechanism

Actinomycin D is primarily used as an investigative tool in cell biology to inhibit transcription. It does this by binding DNA at the transcription initiation complex and preventing elongation by RNA polymerase.[2] Because it can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis.

Clinical use

As chemotherapy

Actinomycin D, marketed under the trade name Dactinomycin, is one of the older chemotherapy drugs which has been used in therapy for many years.

It is a clear, yellow liquid which is administered intravenously and most commonly used in treatment of a variety of cancers including gestational trophoblastic neoplasia,[3] Wilms' tumor[4] and rhabdomyosarcoma.[5]

As an antibiotic

It was the first antibiotic shown to have anti-cancer activity, but is not normally used as such, as it is highly toxic, causing damage to genetic material.

Research use

Actinomycin D and its fluorescent derivative, 7-aminoactinomycin D (7-AAD), are used as stains in microscopy and flow cytometry applications. The affinity of these stains compounds for GC-rich regions of DNA strands makes them excellent markers for DNA. 7-AAD binds to single stranded DNA; therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones.[6]

References

  1. ^ Waksman S A, Woodruff H B (1940). "Bacteriostatic and bacteriocidal substances produced by soil actinomycetes". Proc Soc Exper Biol 45: 609–614. 
  2. ^ Sobell H (1985). "Actinomycin and DNA transcription". Proc Natl Acad Sci USA 82 (16): 5328–31. doi:10.1073/pnas.82.16.5328. PMID 2410919. 
  3. ^ Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose M (2006). "Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia". Int J Gynecol Cancer 16 (3): 1432–8. doi:10.1111/j.1525-1438.2006.00606.x. PMID 16803542. 
  4. ^ Abd El-Aal H, Habib E, Mishrif M (2005). "Wilms' Tumor: The Experience of the Pediatric Unit of Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK)". J Egypt Natl Canc Inst 17 (4): 308–11. PMID 17102824. 
  5. ^ Khatua S, Nair C, Ghosh K (2004). "Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues". J Pediatr Hematol Oncol 26 (11): 777–9. doi:10.1097/00043426-200411000-00020. PMID 15543019. 
  6. ^ 7-Amino-Actinomycin D, Fermentek

External links


 
 
Learn More
Antineoplastic agents
List of drugs: Cm-Co
National Cancer Institute

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Dictionary. The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2007. Published by Houghton Mifflin Company. All rights reserved.  Read more
Oncology Encyclopedia. Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved.  Read more
Drug Info. Gold Standard. Copyright © 2008 by Gold Standard. All rights reserved.  Read more
Veterinary Dictionary. Saunders Comprehensive Veterinary Dictionary 3rd Edition. Copyright © 2007 by D.C. Blood, V.P. Studdert and C.C. Gay, Elsevier. All rights reserved.  Read more
Wikipedia. This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Actinomycin" Read more