DACARBAZINE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Alkylating agent; inhibits DNA and RNA synthesis by forming covalent bonds with DNA, leading to cross-linking and strand breaks. Also inhibits purine synthesis and has some activity as a methylating agent.

What the body does with it

Metabolism	Hepatic; primarily via CYP450 enzymes (CYP1A2, CYP2E1) to active metabolites (e.g., AIC) and inactive metabolites (e.g., HMMT).
Excretion	Renal: 40-50% unchanged; hepatic: 30-50% as metabolites (primarily 5-aminoimidazole-4-carboxamide); <10% fecal.
Half-life	Terminal half-life: 5 hours (range 3-8 h) after IV administration; biphasic decay with initial half-life ~19 min.
Protein binding	20-28% bound to plasma proteins (primarily albumin).
Volume of Distribution	Vd: 1.5-2.0 L/kg, indicating extensive tissue distribution.
Bioavailability	IV: 100% (only route); oral: <1% due to rapid metabolism and poor absorption.
Onset of Action	IV: 3-6 days for antitumor effect (DNA alkylation); clinical response may take 2-4 weeks.
Duration of Action	Duration: 2-4 weeks after a single dose; repeated cycles needed for sustained effect.

Classification & Brands

Dosing & administration

2.4-4.5 mg/kg IV daily for 10 days every 28 days; or 250 mg/m2 IV daily for 5 days every 21 days; or 375-450 mg/m2 IV single dose every 21-28 days.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Severe renal impairment (GFR <30 mL/min): administer 75% of dose; use with caution and monitor for toxicity.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25-50%; Child-Pugh C: contraindicated or avoid use; use with caution and monitor hepatic function.
Pediatric use	200-400 mg/m2 IV daily for 5 days every 21-28 days; or 2.5-6 mg/kg IV daily for 10 days every 28 days. Not established for children <1 year.
Geriatric use	Start at lower end of dosing range (e.g., 200 mg/m2 IV daily for 5 days) due to age-related decreased renal and hepatic function; monitor for myelosuppression and hepatotoxicity.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Phenytoin may reduce efficacy Can cause severe nausea and vomiting and myelosuppression.

Breastfeeding	No data on dacarbazine in human milk. Due to its molecular weight (< 300 Da), excretion is possible. M/P ratio unknown. Discontinue breastfeeding during therapy and for at least 2 weeks after last dose.
Teratogenic Risk	Dacarbazine is teratogenic in animal studies at maternal toxic doses. Human data are limited. First trimester exposure: risk of major malformations (neural tube, cardiovascular) and fetal death. Second/third trimester: fetal growth restriction, preterm birth. Use only if maternal benefit justifies risk.

Warnings & precautions

■ FDA Black Box Warning

Carcinogenicity: Dacarbazine has been associated with an increased risk of secondary malignancies, including myelodysplastic syndrome and acute myeloid leukemia. Healthcare providers should monitor patients for signs of malignancy.

Side Effect Profile

Common Effects	melanoma
Serious Effects

Absolute Contraindications

Hypersensitivity to dacarbazine; severe myelosuppression; pregnancy (due to teratogenicity).

Clinical Precautions

Precautions

Hematologic toxicity (myelosuppression), hepatotoxicity, renal toxicity, carcinogenicity, extravasation (tissue necrosis), and hypersensitivity reactions. Monitor blood counts and liver/renal function.

Clinical Tips & Counseling

Drug interactions

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