Comprehensive Guide to Dacarbazine: Uses, Dosage, Side Effects, and More
What is Dacarbazine?
Overview of Dacarbazine
Generic Name: Dacarbazine
Brand Name: DTIC-Dome, generics
Drug Group: Alkylating agent (antineoplastic)
Commonly Used For
- Treat malignant melanoma.
- Manage Hodgkin’s lymphoma.
- Control metastatic cancers.
Key Characteristics
Form: Lyophilized powder for injection (100 mg, 200 mg/vial) (detailed in Dosage section).
Mechanism: Methylates DNA, disrupting replication and transcription.
Approval: FDA-approved (1975 for DTIC-Dome) and EMA-approved for specific cancers.
Indications and Uses of Dacarbazine
Dacarbazine is indicated for several neoplastic conditions, leveraging its cytotoxic effects to target cancer cells:
Malignant Melanoma: Treats metastatic melanoma, often as a single agent or with other drugs, improving response rates, per oncology guidelines.
Hodgkin’s Lymphoma: Used in the ABVD regimen (with doxorubicin, bleomycin, vinblastine) for advanced Hodgkin’s lymphoma, enhancing remission, supported by hematology trials.
Soft Tissue Sarcoma: Manages metastatic soft tissue sarcomas, reducing tumor growth, used in combination therapy under specialist care.
Neuroblastoma: Employed off-label for high-risk neuroblastoma in children, improving survival when combined with other agents, with pediatric oncology data.
Small Cell Lung Cancer: Investigated off-label as part of multi-drug regimens for small cell lung cancer, enhancing control, supported by pulmonary oncology studies.
Primary CNS Lymphoma: Used off-label in combination therapy for primary central nervous system lymphoma, reducing intracranial lesions, with neurology evidence.
Gastrointestinal Stromal Tumors (GIST): Explored off-label for advanced GIST resistant to imatinib, with cautious use under gastrointestinal oncology supervision.
Merkel Cell Carcinoma: Managed off-label with Dacarbazine to control metastatic Merkel cell carcinoma, with emerging dermatologic oncology data.
Chronic Myelogenous Leukemia (CML): Investigated off-label for CML blast crisis, improving hematologic response, supported by hematology research.
Dosage of Dacarbazine
Dosage for Adults
Malignant Melanoma:
- 2–4.5 mg/kg IV daily for 10 days or 250 mg/m² IV daily for 5 days, repeated every 3–4 weeks.
Hodgkin’s Lymphoma (ABVD):
- 375 mg/m² IV on days 1 and 15 of a 28-day cycle, with other agents.
Soft Tissue Sarcoma:
- 200–250 mg/m² IV daily for 5 days, repeated every 3–4 weeks.
Dosage for Children
Neuroblastoma or Soft Tissue Sarcoma:
- 6.5–12.5 mg/kg IV daily for 5 days or 200–250 mg/m² IV daily for 5 days, under pediatric oncologist supervision.
- Not recommended under 1 year unless critical.
Dosage for Pregnant Women
Pregnancy Category C: Avoid unless benefits outweigh risks (e.g., life-threatening cancer). Consult an obstetrician, with fetal monitoring.
Dosage Adjustments
Renal Impairment: No specific adjustment; monitor in severe cases (CrCl <30 mL/min).
Hepatic Impairment: Reduce dose by 50% if bilirubin >3 mg/dL; avoid if >5 mg/dL.
Elderly: Start with lower end of range (e.g., 200 mg/m²); increase cautiously.
Concomitant Radiation: Reduce dose by 50% if used with radiotherapy due to enhanced toxicity.
Additional Considerations
- Administer this active ingredient via IV infusion over 30–60 minutes by a healthcare provider.
- Premedicate with antiemetics to reduce nausea.
How to Use Dacarbazine
Administration:
- Reconstitute with sterile water, dilute in normal saline or dextrose, and infuse IV over 30–60 minutes; avoid extravasation.
- Administer in a controlled setting with hydration and antiemetics.
Timing: Use as part of a scheduled chemotherapy cycle, typically every 3–4 weeks.
Monitoring: Watch for nausea, fever, or signs of infection (e.g., chills).
Additional Tips:
- Store at 2–8°C (36–46°F); protect from light.
- Handle with gloves; dispose of waste per hazardous drug protocols.
- Report severe pain at injection site, bruising, or signs of liver issues immediately.
Contraindications for Dacarbazine
Hypersensitivity: Patients with a known allergy to Dacarbazine or its components.
Severe Bone Marrow Suppression: Contraindicated due to heightened infection risk.
Severe Hepatic Impairment: Avoid if bilirubin >5 mg/dL.
Pregnancy: Contraindicated unless life-saving.
Warnings & Precautions for Dacarbazine
General Warnings
Myelosuppression: Risk of neutropenia, thrombocytopenia, and anemia; monitor blood counts weekly.
Hepatotoxicity: Risk of hepatic vein thrombosis; check liver function regularly.
Secondary Malignancies: Increased risk with long-term use; inform patients.
Gastrointestinal Toxicity: Severe nausea and vomiting; use aggressive antiemetics.
Extravasation: Tissue damage if leaked; use central lines.
Additional Warnings
Photosensitivity: Increased skin reaction to sunlight; use protection.
Cardiotoxicity: Rare with high doses; monitor ECG.
Infections: High risk due to immunosuppression; prophylaxis may be needed.
Renal Toxicity: Rare nephrotoxicity; monitor kidney function.
Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.
Use in Specific Populations
Pregnancy: Category C; avoid unless critical; use contraception.
Breastfeeding: Avoid due to potential toxicity; monitor infant.
Elderly: Higher risk of toxicity; start with lower doses.
Children: Limited to 1 year+; supervise closely.
Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.
Additional Precautions
- Inform your doctor about liver disease, infections, or prior radiation before starting this medication.
- Avoid live vaccines during therapy.
Overdose and Management of Dacarbazine
Overdose Symptoms
- Nausea, vomiting, or severe myelosuppression.
- Severe cases: Liver failure, renal impairment, or sepsis.
- Fever, fatigue, or bruising as early signs.
- Cardiac arrest with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer IV fluids, blood transfusions, and antibiotics if infected.
Specific Treatment: No antidote; manage symptoms and monitor organ function.
Monitor: Check blood counts, liver enzymes, and vital signs for 7–14 days.
Additional Notes
- Overdose risk is high; store securely.
- Report persistent symptoms (e.g., jaundice, severe weakness) promptly.
Side Effects of Dacarbazine
Common Side Effects
- Nausea (80–90%, managed with antiemetics)
- Vomiting (70–85%, reduced with hydration)
- Fatigue (40–60%, decreases with rest)
- Anorexia (30–50%, improved with nutrition support)
- Hair Loss (20–40%, reversible post-treatment)
These effects may subside with dose adjustment or cycle breaks.
Serious Side Effects
Seek immediate medical attention for:
- Hematologic: Neutropenia, thrombocytopenia, or anemia.
- Hepatic: Hepatic vein thrombosis or jaundice.
- Gastrointestinal: Severe vomiting, diarrhea, or bowel obstruction.
- Infectious: Sepsis or opportunistic infections.
- Allergic: Rash, angioedema, or anaphylaxis.
Additional Notes
- Regular monitoring for blood counts, liver function, and infection risk is advised.
- Report any unusual symptoms (e.g., fever, severe abdominal pain) immediately to a healthcare provider.
Drug Interactions with Dacarbazine
This active ingredient may interact with:
- Live Vaccines: Reduces immune response; avoid.
- Hepatotoxic Drugs: Enhances liver damage (e.g., alcohol); monitor.
- CYP1A2 Inhibitors: Increases levels (e.g., ciprofloxacin); adjust dose.
- Anticoagulants: Alters bleeding risk; monitor INR.
- Radiation Therapy: Potentiates toxicity; reduce dose.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Take this alkylating agent as prescribed in chemotherapy cycles, following the exact schedule.
Monitoring: Report fever, bruising, or yellowing skin immediately.
Lifestyle: Avoid sun exposure; use sunscreen and protective clothing.
Diet: Take with antiemetics; avoid heavy meals during nausea.
Emergency Awareness: Know signs of infection or liver failure; seek care if present.
Follow-Up: Schedule regular check-ups every 1–2 weeks during therapy to monitor blood and liver health.
Pharmacokinetics of Dacarbazine
Absorption: Poor oral bioavailability; administered IV (peak not applicable).
Distribution: Volume of distribution ~0.5 L/kg; 5% protein-bound.
Metabolism: Hepatic via CYP1A2 to active metabolites (e.g., MTIC).
Excretion: Primarily renal (40%) as unchanged drug and metabolites; half-life 5 hours.
Half-Life: 5 hours, with rapid clearance but prolonged effects.
Pharmacodynamics of Dacarbazine
This drug exerts its effects by:
Methylating DNA guanine, inhibiting replication and transcription.
Inducing apoptosis in cancer cells.
Demonstrating dose-dependent myelosuppression and gastrointestinal toxicity.
Exhibiting enhanced effects with combination chemotherapy.
Storage of Dacarbazine
- Temperature: Store at 2–8°C (36–46°F); protect from light.
- Protection: Keep in original container, away from heat.
- Safety: Store in a locked container out of reach of children due to toxicity risk.
- Disposal: Dispose of unused vials per hazardous drug regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Dacarbazine treat?
A: This medication treats melanoma and Hodgkin’s lymphoma.
Q: Can this active ingredient cause hair loss?
A: Yes, hair loss may occur; it’s usually temporary.
Q: Is Dacarbazine safe for children?
A: Yes, for 1 year+ with a doctor’s guidance.
Q: How is this drug taken?
A: Via IV infusion, as directed by a healthcare provider.
Q: How long is Dacarbazine treatment?
A: Varies by cancer type, often in cycles.
Q: Can I use Dacarbazine if pregnant?
A: No, avoid unless life-saving; consult a doctor.
Regulatory Information for Dacarbazine
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 1975 (DTIC-Dome) for melanoma and Hodgkin’s lymphoma.
European Medicines Agency (EMA): Approved for specific cancers.
Other Agencies: Approved globally for oncology; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). DTIC-Dome (Dacarbazine) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Dacarbazine Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Dacarbazine: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Dacarbazine.
- WHO’s inclusion of Dacarbazine for cancer therapy.
- Journal of Clinical Oncology. (2022). Dacarbazine in Melanoma Therapy.
- Peer-reviewed article on Dacarbazine efficacy (note: access may require a subscription).
