DTIC-DOME
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DTIC-DOME (DTIC-DOME).
Dacarbazine is an alkylating agent that forms methyltriazenoimidazole carboxamide, causing cross-linking of DNA and inhibition of DNA, RNA, and protein synthesis.
| Metabolism | Hepatic metabolism via demethylation by cytochrome P450 enzymes; also undergoes spontaneous decomposition to active metabolites. |
| Excretion | Renal (40-60% as unchanged drug and metabolites, primarily 5-aminoimidazole-4-carboxamide); biliary/fecal (minimal, <10%) |
| Half-life | Terminal elimination half-life is approximately 5 hours (range 4-7 hours) for parent drug; metabolites exhibit longer half-life (up to 8-12 hours). Clinical context: requires multiple dosing cycles due to short half-life. |
| Protein binding | Approximately 20-30% bound to plasma proteins (albumin). |
| Volume of Distribution | 0.6-1.2 L/kg, indicating extensive distribution into total body water and tissues. |
| Bioavailability | Intravenous: 100% (only route of administration; not administered orally due to poor oral bioavailability <5%). |
| Onset of Action | Intravenous: clinical effect (antitumor response) observed within 2-4 weeks after initiation of therapy. |
| Duration of Action | Duration of action is approximately 4-6 weeks per cycle, with repeated cycles required for sustained effect; myelosuppression nadir occurs at 2-4 weeks. |
DTIC 250 mg/m2 IV daily for 5 days every 21-28 days, or 850-1000 mg/m2 IV as a single dose every 21-28 days.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: Administer 75% of dose. CrCl <10 mL/min: Administer 50% of dose. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 25-50%. Child-Pugh C: Avoid use or reduce dose by 75%. |
| Pediatric use | 200-250 mg/m2 IV daily for 5 days every 21-28 days. |
| Geriatric use | No specific dose adjustment recommended; monitor renal and hepatic function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DTIC-DOME (DTIC-DOME).
| Breastfeeding | No human data available; M/P ratio not determined. Dacarbazine is excreted in rat milk. Due to potential for severe adverse effects (myelosuppression, carcinogenicity), breastfeeding is contraindicated during therapy and for at least 2 weeks after last dose. |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: high risk of teratogenicity, including structural anomalies (cleft palate, skeletal defects). Second and third trimesters: fetal myelosuppression, growth restriction, and increased risk of spontaneous abortion due to cytotoxic effects. Avoid in pregnancy unless potential benefit outweighs severe fetal risk. |
■ FDA Black Box Warning
DTIC-Dome should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Hemopoietic depression is a frequent and serious toxicity. Hepatic necrosis and veno-occlusive liver disease have been reported.
| Serious Effects |
Hypersensitivity to dacarbazine, severe myelosuppression, and concurrent administration with yellow fever vaccine.
| Precautions | Bone marrow suppression (leukopenia, thrombocytopenia, anemia), hepatotoxicity including hepatic necrosis, hypersensitivity reactions, renal toxicity, and photosensitivity. Pregnancy category D. |
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| Fetal Monitoring | Maternal: complete blood count with differential, liver function tests, renal function tests, and uric acid levels prior to each cycle; monitor for severe nausea/vomiting, fluid/electrolyte imbalance. Fetal: serial ultrasound for growth, anatomy, and amniotic fluid volume if used during pregnancy; consider fetal echocardiography if first trimester exposure. |
| Fertility Effects | Gonadal toxicity; high risk of transient or permanent azoospermia in males and ovarian failure in females (premature menopause). May cause amenorrhea, reduced fertility, and teratospermia. Pre-treatment fertility preservation counseling recommended. |