Dacarbazine

Source: Wikipedia, the free encyclopedia.

Dacarbazine
Clinical data
Pronunciation/dəˈkɑːrbəˌziːn/
Trade namesDTIC-Dome, others
Other namesDTIC[1]
AHFS/Drugs.comMonograph
MedlinePlusa682750
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
  • US: WARNING[2]Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability100%
MetabolismExtensive
Elimination half-life5 hours
ExcretionKidney (40% as unchanged dacarbazine)
Identifiers
  • 5-(3,3-Dimethyl-1-triazenyl)imidazole-4-carboxamide
JSmol)
  • CN(C)N=Nc1[nH]cnc1C(N)=O
  • InChI=1S/C6H10N6O/c1-12(2)11-10-6-4(5(7)13)8-3-9-6/h3H,1-2H3,(H2,7,13)(H,8,9)/b11-10+ checkY
  • Key:FDKXTQMXEQVLRF-ZHACJKMWSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Dacarbazine, also known as imidazole carboxamide and sold under the brand name DTIC-Dome, is a

injection into a vein.[3]

Common side effects include loss of appetite, vomiting,

purine analog families of medication.[3]

Dacarbazine was approved for medical use in the United States in 1975.[3] It is on the World Health Organization's List of Essential Medicines.[4]

Medical uses

As of mid-2006, dacarbazine is commonly used as a single agent in the treatment of

Hodgkin's lymphoma,[7] and in the MAID regimen for sarcoma.[8][9] Dacarbazine was proven to be just as efficacious as procarbazine,[10] another drug with similar chemistry, in the German trial for paediatric Hodgkin's lymphoma, without the teratogenic effects.[citation needed] Thus COPDAC has replaced the former COPP regime in children for TG2 & 3 following OEPA.[11]

Side effects

Like many chemotherapy drugs, dacarbazine may have numerous serious side effects, because it interferes with normal cell growth as well as cancer cell growth. Among the most serious possible side effects are birth defects to children conceived or carried during treatment; sterility, possibly permanent; or immune suppression (reduced ability to fight infection or disease). Dacarbazine is considered to be highly emetogenic,[12] and most patients will be pre-medicated with dexamethasone and antiemetic drugs like 5-HT3 antagonist (e.g., ondansetron) and/or NK1 receptor antagonist (e.g., aprepitant). Other significant side effects include headache, fatigue and occasionally diarrhea.

The Swedish National Board of Health and Welfare has sent out a black box warning and suggests avoiding dacarbazine due to liver problems.[13]

Mechanism of action

Dacarbazine is activated by liver microsomal enzymes to monomethyl triazeno imidazole carboxamide (MTIC), which is an alkylating compound.[14] It causes methylation, modification and cross linking of DNA, thus inhibiting DNA, RNA and protein synthesis.[15]

Synthesis

Nitrous acid is added to 5-aminoimidazol-4-carboxamide to make 5-diazoimidazol-4-carboxamide. It reacts with dimethylamine to give dacarbazine.[16]

History

See also: History of cancer chemotherapy

In 1959, dacarbazine was first synthesized at Southern Research in Alabama.[17] The research was funded by a US federal grant. Dacarbazine gained FDA approval in May 1975 as DTIC-Dome. The drug was initially marketed by Bayer.

Society and culture

There are

Teva
.

References

  1. ISBN 978-1-4757-2087-7
    .
  2. FDA
    . Retrieved October 22, 2023.
  3. ^ a b c d e f g h "Dacarbazine". The American Society of Health-System Pharmacists. Archived from the original on September 11, 2017. Retrieved December 8, 2016.
  4. hdl:10665/371090
    . WHO/MHP/HPS/EML/2023.02.
  5. PMID 10840932
    .
  6. PMID 19544689
    .
  7. PMID 15550585
    .
  8. PMID 2110385
    .
  9. S2CID 25246937
    .
  10. S2CID 32031568
    .
  11. PMID 20625128
    .
  12. PMID 24649120
    .
  13. ^ "Alla aktuella ändringar för Dacarbazine medac Pulver till infusionsvätska, lösning 500 mg, Medac". FASS.se. Archived from the original on October 1, 2011. Retrieved August 19, 2011.
  14. PMID 24284332
    .
  15. PMID 31644220
    .
  16. ISBN 9780444521668
    .
  17. PMID 17897837
    .
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