DACARBAZINE
Clinical safety rating: avoid
Contraindicated (not allowed)
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.
| 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. |
| Molecular Weight | 182.18 |
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. |
| 1st trimester | Dacarbazine is teratogenic in animals and should be avoided in the first trimester unless absolutely necessary. Human data limited; risk of fetal harm cannot be excluded. |
| 2nd trimester | Use only if potential benefit justifies potential risk to fetus. May cause fetal harm. |
| 3rd trimester | Use only if potential benefit justifies potential risk to fetus. May cause fetal harm, including low birth weight and neonatal myelosuppression. |
Clinical note
Phenytoin may reduce efficacy Can cause severe nausea and vomiting and myelosuppression.
| Placental transfer | Dacarbazine crosses the placenta. Animal studies show significant transfer and fetal toxicity. Human data limited but indicates placental passage. |
| Breastfeeding | Dacarbazine is excreted into breast milk in low concentrations. Because of potential serious adverse reactions in nursing infants (including myelosuppression and carcinogenesis), breastfeeding is not recommended during therapy and for at least 3 days after the last dose. |
■ 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.
| Common Effects | melanoma |
| Serious Effects |
Hypersensitivity to dacarbazineSevere myelosuppressionPregnancy (unless clearly needed)
| Precautions | Hematologic toxicity (myelosuppression), hepatotoxicity, renal toxicity, carcinogenicity, extravasation (tissue necrosis), and hypersensitivity reactions. Monitor blood counts and liver/renal function. |
| Food/Dietary | Avoid alcohol due to potential hepatotoxicity. No specific food interactions reported, but patients should maintain adequate hydration. Grapefruit juice may theoretically inhibit CYP1A2 and alter metabolism, though clinical significance is unclear; it is prudent to avoid. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| Fetal Monitoring | Maternal: CBC, liver and renal function, LDH, uric acid before each cycle. Monitor for myelosuppression, hepatotoxicity, renal toxicity. Fetal: serial ultrasound for growth, anatomy, and amniotic fluid volume. |
| Fertility Effects | Dacarbazine is gonadotoxic. In males: oligospermia/azoospermia with potential reversibility over years. In females: ovarian failure, premature menopause, reduced fertility. Amenorrhea common. Consider fertility preservation. |
| Clinical Pearls | Dacarbazine is commonly used in Hodgkin lymphoma (ABVD regimen) and metastatic melanoma. It is a prodrug requiring hepatic activation via CYP1A2 and CYP2E1. Avoid concurrent use with CYP1A2 inducers (e.g., smoking) or inhibitors. Extravasation causes severe tissue injury; administer via central line if possible. Administer antiemetics pre-emptively due to high emetogenicity. Monitor for myelosuppression, especially leukopenia and thrombocytopenia, with nadir at 2-4 weeks. Hepatic toxicity and flu-like syndrome (fever, myalgia, malaise) are common. Rare but serious: hepatic veno-occlusive disease and secondary malignancies (e.g., myelodysplasia). |
| Patient Advice | This medication is a chemotherapy drug used to treat certain cancers like Hodgkin lymphoma and melanoma. · You may experience nausea and vomiting; take anti-nausea medicines as prescribed and avoid eating large meals before treatment. · Report any signs of infection (fever, chills, sore throat) or unusual bleeding/bruising immediately. · Avoid sun exposure and use sunscreen; this drug may cause photosensitivity. · You may feel tired or have flu-like symptoms (fever, muscle aches) a few days after treatment; rest and stay hydrated. · Do not take any other medications, including over-the-counter products or herbal supplements, without consulting your doctor. · Women should avoid pregnancy and men should avoid fathering a child during treatment; use effective contraception. · Tell your doctor if you experience yellowing of skin/eyes, dark urine, or abdominal pain, as liver problems may occur. |