DTIC

DTIC Uses, Dosage, Side Effects, Food Interaction and all others data.

DTIC is a non-cell cycle specific antineoplastic agent. The exact mechanism of action by which it exerts cytotoxic effects is still unclear. However, three possible mechanisms have been postulated, including inhibition of DNA synthesis by acting as a purine analog, action as an alkylating agent, and interaction with sulfydryl group in the inhibition of bacterial cell growth.

DTIC is a synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC). After intravenous administration of dacarbazine, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. 1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. 1 The average cumulative excretion of unchanged DTIC in the urine is 40% of the injected dose in 6 hours. 1 DTIC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein.

Trade Name DTIC
Availability Prescription only
Generic Dacarbazine
Dacarbazine Other Names Biocarbazine, Dacarbazin, Dacarbazina, Dacarbazine, Dacarbazinum, DTIC, ICDMT
Related Drugs Keytruda, pembrolizumab, doxorubicin, cyclophosphamide, Opdivo, nivolumab, atezolizumab, ipilimumab, Yervoy
Type
Formula C6H10N6O
Weight Average: 182.187
Monoisotopic: 182.091608966
Protein binding

Less than 5%

Groups Approved, Investigational
Therapeutic Class Cytotoxic Chemotherapy
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
DTIC
DTIC

Uses

DTIC is used for the treatment of metastatic malignant melanoma. In addition, DTIC is also used for Hodgkin’s disease as a second-line therapy when used in combination with other effective agents

DTIC is also used to associated treatment for these conditions: Advanced Soft Tissue Sarcoma, Lymphoma, Hodgkins, Metastatic Melanoma, Pheochromocytomas, Advanced Medullary thyroid cancer, Advanced Pancreatic neuroendocrine tumor

How DTIC works

The mechanism of action is not known, but appears to exert cytotoxic effects via its action as an alkylating agent. Other theories include DNA synthesis inhibition by its action as a purine analog, and interaction with SH groups. DTIC is not cell cycle-phase specific.

Dosage

DTIC dosage

Malignant Melanoma: The recommended dosage is 2 to 4.5 mg/kg/day for 10 days. Treatment may be repeated at 4 week intervals. An alternate recommended dosage is 250 mg/m<sup>2</sup>/day IV for 5 days. Treatment may be repeated every 3 weeks.

Hodgkin’s Disease: The recommended dosage of DTICin the treatment of Hodgkin’s disease is 150 mg/m<sup>2</sup>/day for 5 days, in combination with other effective drugs. Treatment may be repeated every 4 weeks. An alternative recommended dosage is 375 mg/m<sup>2</sup> on day 1, in combination with other effective drugs, to be repeated every 15 days.

DTIC 200 mg/vial is reconstituted with 19.7 mL of Sterile Water for Injection. The resulting solution contains 10 mg/mL of dacarbazine having a pH of 3.0 to 4.0. The calculated dose of the resulting solution is drawn into a syringe and administered only intravenously. The reconstituted solution may be further diluted with 5% dextrose injection or sodium chloride injection and administered as an intravenous infusion. After reconstitution and prior to use, the solution in the vial may be stored at 4°C for up to 72 hours or at normal room conditions (temperature and light) for up to 8 hours. If the reconstituted solution is further diluted in 5% dextrose injection or sodium chloride injection, the resulting solution may be stored at 4°C for up to 24 hours or at normal room conditions for up to 8 hours. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. There is no general agreement that all the procedures recommended in the guidelines are necessary or appropriate.

Side Effects

Symptoms of anorexia, nausea and vomiting are the most frequently noted of all toxic reactions. Over 90% of patients are affected with the initial few doses. The vomiting lasts 1 to 12 hours and is incompletely and unpredictably palliated with phenobarbital and/or prochlorperazine. Rarely, intractable nausea and vomiting have necessitated discontinuance of therapy with DTIC for Injection. Rarely, DTIC for Injection has caused diarrhea. Some helpful suggestions include restricting the patient’s oral intake of food for 4 to 6 hours prior to treatment. The rapid toleration of these symptoms suggests that a central nervous system mechanism may be involved, and usually these symptoms subside after the first 1 or 2 days.

Toxicity

LD50=350mg/kg (orally in mice)

Precaution

Hospitalization is not always necessary but adequate laboratory study capability must be available. Extravasation of the drug subcutaneously during intravenous administration may result in tissue damage and severe pain. Local pain, burning sensation and irritation at the site of injection may be relieved by locally applied hot packs. Carcinogenicity of dacarbazine was studied in rats and mice. Proliferative endocardial lesions, including fibrosarcomas and sarcomas were induced by dacarbazine in rats. In mice, administration of dacarbazine resulted in the induction of angiosarcomas of the spleen.

Interaction

Increased metabolism when used with enzyme inducers (e.g. barbiturates, rifampicin, phenytoin). May potentiate the effect of mercaptopurine, azathioprine, allopurinol. May impair immune response to vaccines. May enhance the effects of methoxsalen due to photosensitisation.

Food Interaction

  • Take on an empty stomach. Fasting for four to six hours before treatment may be beneficial to reduce nausea and vomiting associated with DTIC therapy.

Elimination Route

Erratic, slow and incomplete.

Half Life

5 hours

Elimination Route

DTIC is subject to renal tubular secretion rather than glomerular filtration. In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole -4 carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine.

Pregnancy & Breastfeeding use

Pregnancy Category C. DTIC for Injection has been shown to be teratogenic in rats when given in doses 20 times the human daily dose on day 12 of gestation. DTIC when administered in 10 times the human daily dose to male rats (twice weekly for 9 weeks) did not affect the male libido, although female rats mated to male rats had higher incidence of resorptions than controls. In rabbits, dacarbazine daily dose 7 times the human daily dose given on Days 6 to 15 of gestation resulted in fetal skeletal anomalies. There are no adequate and well controlled studies in pregnant women. DTIC for Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for DTIC for Injection in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Contraindication

DTIC is contraindicated in patients who have demonstrated a hypersensitivity to it in the past.

Acute Overdose

Give supportive treatment and monitor blood cell counts.

Storage Condition

Store in a refrigerator 2°C to 8°C

Innovators Monograph

You find simplified version here DTIC

DTIC contains Dacarbazine see full prescribing information from innovator DTIC Monograph, DTIC MSDS, DTIC FDA label

http://classyfire.wishartlab.com/tax_nodes/C0000000
http://classyfire.wishartlab.com/tax_nodes/C0000264
http://classyfire.wishartlab.com/tax_nodes/C0000265
http://classyfire.wishartlab.com/tax_nodes/C0001093
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http://classyfire.wishartlab.com/tax_nodes/C0003890
http://classyfire.wishartlab.com/tax_nodes/C0004144
http://classyfire.wishartlab.com/tax_nodes/C0001662
http://classyfire.wishartlab.com/tax_nodes/C0003633
http://classyfire.wishartlab.com/tax_nodes/C0004139
http://classyfire.wishartlab.com/tax_nodes/C0000323
http://classyfire.wishartlab.com/tax_nodes/C0000278
http://classyfire.wishartlab.com/tax_nodes/C0003940
http://classyfire.wishartlab.com/tax_nodes/C0004150
http://www.genome.jp/dbget-bin/www_bget?drug:D00288
http://www.genome.jp/dbget-bin/www_bget?cpd:C06936
https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5351166
https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507029
https://www.chemspider.com/Chemical-Structure.10481959.html
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50238687
https://mor.nlm.nih.gov/RxNav/search?searchBy=RXCUI&searchTerm=3098
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=4305
https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL476
https://zinc.docking.org/substances/ZINC000100019007
http://bidd.nus.edu.sg/group/cjttd/ZFTTDDRUG.asp?ID=DAP000533
http://www.pharmgkb.org/drug/PA449197
http://www.rxlist.com/cgi/generic2/dacarbazine.htm
https://www.drugs.com/cdi/dacarbazine.html
https://en.wikipedia.org/wiki/Dacarbazine
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