Dosing and uses of DTIC Dome (dacarbazine)
Adult dosage forms and strengths
powder for injection
- 100mg
- 200mg
Hodgkin's Disease
With other antineoplastics, eg ABVd
Dosage dependent on protocoL
150 mg/m² IV qDay for 5 days, repeat q4Weeks Or
375 mg/m² IV on Day 1; repeat every 15 Days
Monitor: CBC, LFTs
Metastatic Malignant Melanoma
2-4.5 mg/kg IV qDay for 10 days, repeat q4Weeks Or
250 mg/m² IV qDay for 5 days, repeat q3Weeks
Monitor: CBC, LFTs
Renal Impairment
CrCl 46-60 mL/min: 80% of regular dose
CrCl 31-45 mL/min: 75% of regular dose
CrCl <30 mL/min: 70% of regular dose
Hepatic Impairment
Not studied; monitor for signs of liver toxicity
Other Indications & Uses
Off-label: Soft-tissue sarcomas, thyroid cancer, neuroblastoma
Pediatric dosage forms and strengths
powder for injection
- 100mg
- 200mg
Hodgkin's Disease
With other antineoplastics, eg ABVd
Dosage dependent on protocol150 mg/m² IV qDay for 5 days, repeat q4Weeks Or
375 mg/m² IV on Day 1; repeat every 15 Days
Neuroblastoma Combination Therapy (Off-label)
800-900 mg/m² IV once on day 1; may repeat q3-4weeks
Geriatric dosage forms and strengths
Hodgkin's Disease
With other antineoplastics, eg ABVd
Dosage dependent on protocoL
150 mg/m² IV qDay for 5 days, repeat q4Weeks Or
375 mg/m² IV on Day 1; repeat every 15 Days
Monitor: CBC, LFTs
Metastatic Malignant Melanoma
2-4.5 mg/kg IV qDay for 10 days, repeat q4Weeks Or
250 mg/m² IV qDay for 5 days, repeat q3Weeks
Monitor: CBC, LFTs
DTIC Dome (dacarbazine) adverse (side) effects
>10%
Nausea (>90%)
Vomiting(>90%)
Injection site pain
Leukopenia
Thrombocytopenia
1-10%
Alopecia
Rash
Photosensitivity
Anorexia
Metallic taste
Flu-like syndrome
Frequency not defined
Anaphylaxis
Photosensitivity (rare)
Cerebral hemorrhage
Seizure
Myelosuppression
Hepatic necrosis
Hepatic vein thrombosis
Hepatotoxicity
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician.
The most common toxicity for injectable dacarbazine is hemopoietic (bone marrow) depression
Hepatic necrosis reported
Carcinogenic and teratogenic effects reported in animals.
The physician must weigh the possible therapeutic benefits against the risks of toxicity.
Contraindications
Hypersensitivity
Breastfeeding
Severe anemia, severe thrombocytopenia
Cautions
Caution in hepatic/renal impairment; monitor for toxicity
May cause severe pain & burning at injection site & along vein; to alleviate, may increase diluent, reduce infusion rate & apply cold compresses
Risk of potentially fatal hepatocellular necrosis
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of DTIC Dome (dacarbazine)
Mechanism of action
Non-cell cycle specific; alkylates DNA & RNA; causes DNA double strand breaks and apoptosis
Pharmacokinetics
Half-Life: 5 hr (terminal)
Peak Plasma: 8 mcg/mL (4.5 mg/kg dose)
Protein Bound: ~5%
Vd: 0.6 L/kg
Metabolism: Liver
Metabolites: 5-(3-monomethyl-1-triazenyl)-1H-imidazole-4-carboxamide (MIC)
Excretion: Urine (~40%)
Administration
IV Incompatibilities
Additive: hydrocortisone sodium succinate
Y-site: allopurinol, cefepime, piperacillin/tazobactam
IV Compatibilities
Solution: D5W(?)
Additive: ondansetron
Y-site: amifostine, aztreonam, doxorubicin liposomal, etoposide PO4, filgrastim, fludarabine, granisetron, heparin (at dacarbazine 10 mg/mL; incompatible at 25 mg/mL), melphalan, ondansetron, paclitaxel, sargramostim, teniposide, thiotepa, vinorelbine
IV Preparation
Reconstitute with a 9.9 mL (100 mg vial) or 19.7 mL (200 mg vial) of SWI to obtain a 10 mg/mL soln
For infusion, dilute with D5W or NS up to 250 mL
IV Administration
IVP over 1 min (may be irritant & painful) OR infusion over 15-60 min
Rapid infusion may cause severe venous irritation
Has also been given intraarteriaL
Extravasation Management
Local pain, burning sensation & irritation at injection site may be relieved by local application of hot packs
If extravasation occurs, apply cold packs
Protect exposed tissue from light following extravasation
Storage
Store intact vials under refrigeration
Protect from light