dacarbazine (da-kar-ba-zeen) DTIC, DTIC-Dome

 Indications

Treatment of metastatic malignant melanoma (single

agent). Treatment of Hodgkin’s disease as second-line

therapy (with other agents).

Action

Disrupts DNA and RNA synthesis (cell-cycle phase–

nonspecific). Therapeutic Effects: Death of rapidly

growing tissue cells, especially malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete

bioavailability.

Distribution: Large volume of distribution; probably

concentrates in liver; some CNS penetration.

Metabolism and Excretion: 50% metabolized by

the liver, 50% excreted unchanged by the kidneys.

Half-life: 5 hr (qin renal and hepatic dysfunction). 

TIME/ACTION PROFILE (effects on blood

counts)

ROUTE ONSET PEAK DURATION

IV (WBCs) 16–20 days 21–25 days 3–5 days

IV (platelets) unknown 16 days 3–5 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity; OB, Lactation:

Pregnancy or lactation.

Use Cautiously in: Active infections; Bone marrow

depression; Pedi: Children (safety not established); Renal

dysfunction; Hepatic dysfunction.

Adverse Reactions/Side Effects

GI: HEPATIC NECROSIS, anorexia, nausea, vomiting, diarrhea,

hepatic vein thrombosis. Derm: alopecia, facial

flushing, photosensitivity, rash. Endo: gonadal suppression.

Hemat: anemia, leukopenia, thrombocytopenia.

Local: pain at IV site, phlebitis at IV site, tissue

necrosis. MS: myalgia. Neuro: facial paresthesia.

Misc: ANAPHYLAXIS, fever, flu-like syndrome, malaise.

Interactions

Drug-Drug: Additive bone marrow depression with

other antineoplastics. Carbamazepine, phenobarbital,

and rifampin mayqmetabolism and decrease

effectiveness. Blood levels may beqwith amiodarone,

ciprofloxacin, fluvoxamine, ketoconazole, ofloxacin,

isoniazid, or miconazole. Maypantibody response

to live-virus vaccines andqrisk of adverse

reactions.

Route/Dosage

Other regimens are used.

IV (Adults): Malignant melanoma—2–4.5 mg/kg/

day for 10 days administered every 4 wk or 250 mg/m2/

day for 5 days administered every 3 wk. Hodgkin’s disease—

150 mg/m2/day for 5 days (in combination with

other agents) administered every 4 wk or 375 mg/m2

(in combination with other agents) administered every

15 days.

Availability

Powder for injection: 200 mg.