Dazine

Dacarbazine is an anticancer agent.

Although the exact mechanism of action of dacarbazine is not known, three hypotheses put forth are:

1) Inhibition of DNA synthesis by acting as a purine analog

2) Action as an alkylating agent

3) Interaction with SH groups

Dazine is indicated in the treatment of

• Metastatic malignant melanoma

• Hodgkin's disease as a secondary-line therapy when used in combination with other effective agents

• Neuroblastoma

• Soft-tissue sarcoma, including leiomyosarcoma

After intravenous administration of DTIC-Dome, 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

• Terminal half-life of 5 hours

In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to:

• 55 minutes

• 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 DTIC is not appreciably bound to human plasma protein.

In man, DTIC is extensively degraded.

Besides unchanged DTIC, 5-aminoimidazole-4-carboxamide (AIC) is a major metabolite of DTIC excreted in the urine.

AIC is not derived endogenously but from the injected DTIC, because the administration of radioactive DTIC labeled with 14C in the imidazole portion of the molecule (DTIC-2-14C) gives rise to AIC-2-14C.

Hepatic toxicity accompanied by hepatic vein thrombosis and hepatocellular necrosis resulting in death has been observed mostly when dacarbazine has been administered concomitantly with other antineoplastic drugs.

However, it has also been reported in some patients treated with DTIC-Dome alone.

Anaphylaxis can occur following the administration of dacarbazine.

Malignant Melanoma

The recommended dosage of Dazine 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/square meter body surface/day IV for 5 days.

Treatment may be repeated every 3 weeks.

Hodgkin's Disease

The recommended dosage of Dazine 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 metre of body surface on day 1

in combination with other effective drugs, to be repeated every 15 days.

Other

Combination with other antineoplastic agents.

Dosage of Dazine must be based on the clinical haematologic response and tolerance of the patient in order to obtain optimal therapeutic results.

Dacarbazine 100 mg/vial, 200 mg/vial and 500 mg/vial are reconstituted with:

• 9.9 ml
• 19.7 ml
• 50 ml

respectively 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.