DTI

An antineoplastic agent.

It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564).

Dacarbazine with

Oblimersen is in clinical trials for the treatment of malignant melanoma.

For the treatment of metastatic malignant melanoma.

In addition, dacarbazine is also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other antineoplastic agents.

Dacarbazine 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.

In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours.

The average cumulative excretion of unchanged

DTIC in the urine is 40% of the injected dose in 6 hours.

DTIC is subject to renal tubular secretion rather than glomerular filtration.

At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein.

Erratic, slow and incomplete.

Dacarbazine 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.

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Give supportive treatment and monitor blood cell counts.

Hemopoietic depression is the most common toxicity with dacarbazine and involves primarily the leukocytes and platelets, although, anemia may sometimes occur.

Leukopenia and thrombocytopenia may be severe enough to cause death.

The possible bone marrow depression requires careful monitoring of white blood cells, red blood cells, and platelet levels.

Hemopoietic toxicity may warrant temporary suspension or cessation of therapy with dacarbazine.

Hepatic toxicity accompanied by hepatic vein thrombosis and hepatocellular necrosis resulting in death, has been reported.

The incidence of such reactions has been low; approximately 0.01% of patients treated.

This toxicity has been observed mostly when dacarbazine has been administered concomitantly with other anti-neoplastic drugs; however, it has also been reported in some patients treated with dacarbazine alone.

Anaphylaxis can occur following the administration of dacarbazine.

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

The recommended dosage is to 4.5 mg/kg/day for 10 days.

Treatment may be repeated at 4 week intervals.

An alternate recommended dosage is 250 mg/square meter body surface/day I.V. for 5 days.

Treatment may be repeated every 3 weeks.

Hodgkin's Disease The recommended dosage of dacarbazine in the treatment of Hodgkin's disease is 150 mg/square meter body surface/day for 5 days, in combination with other effective drugs.

Treatment may be repeated every 4 weeks.

An alternative recommended dosage is 375 mg/square meter body surface on day 1, in combination with other effective drugs, to be repeated every 15 days.

Dacarbazine 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. 1-7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration whenever solution and container permit.

Dacarbazine for

Injection, USP is supplied as follows: NDC 0143-9245-10 200 mg/vial of sterile dacarbazine in boxes of 10.

Store in a refrigerator 2° to 8°C (36° to 46°F).

To report SUSPECTED ADVERSE

REACTIONS, contact Hikma Pharmaceuticals USA Inc.fda.gov/medwatch.

Inquiry call 1-877-845-0689.

Teratogenic effects; Pregnancy Category C Dacarbazine has been shown to be teratogenic in rats when given in doses 20 times the human daily dose on day of gestation.

Dacarbazine 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 to 15 of gestation resulted in fetal skeletal anomalies.

There are no adequate and well-controlled studies in pregnant women.

Dacarbazine 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 dacarbazine 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.