Generic Name

Dacarbazine

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Classification

FDA Approved Indications

• Malignant melanoma
• Hodgkin’s lymphoma
• Soft tissue sarcomas

Mechanism of Action

Dacarbazine is a prodrug that requires metabolic activation to produce its active metabolites, which methylate DNA, leading to cross-linking and strand breakage, resulting in cell death, particularly in rapidly dividing cells.

Dosage and Administration

Adult: The typical dose is 250-850 mg/m² IV every 3-4 weeks, depending on the indication and patient tolerance.

Pediatric: Dosing varies based on body surface area and condition; consult specific protocols.

Geriatric: Use with caution; adjust dose based on renal and hepatic function.

Renal Impairment: Adjust dosage based on renal function; no specific guidelines—monitor closely.

Hepatic Impairment: Adjust dose in hepatic impairment; no definitive guidelines, caution advised.

Pharmacokinetics

Absorption: Administered IV; not absorbed orally.

Distribution: Widely distributed; crosses the blood-brain barrier.

Metabolism: Hepatically metabolized to active metabolites.

Excretion: Primarily via the urine.

Half Life: Approximately 5-7 hours.

Contraindications

• Hypersensitivity to dacarbazine or other alkylating agents.
• Bone marrow suppression.
• Pregnancy (see pregnancy/lactation guidance).

Precautions

• Use with caution in hepatic or renal impairment, during active infections, or in patients with myelosuppression.

Adverse Reactions - Common

• Nausea and vomiting (Very common)
• Bone marrow suppression (Common)
• Fatigue (Common)

Adverse Reactions - Serious

• Severe myelosuppression leading to infection or bleeding (Serious)
• Liver toxicity, including hepatitis and hepatic failure (Serious)
• Secondary malignancies, such as leukemia (Long-term risk)

Drug-Drug Interactions

• CNS depressants, other myelosuppressive agents, phenytoin

Drug-Food Interactions

• None well established

Drug-Herb Interactions

• Limited data; caution advised.

Nursing Implications

Patient/Family Teaching

• Report fever, sore throat, unusual bleeding, or unexplained bruising.
• Use effective antiemetics and eat small, frequent meals if nausea occurs.
• Avoid pregnancy and use effective contraception.

Special Considerations

Black Box Warnings:

• Myelosuppression leading to serious or fatal infections, bleeding, or anemia.
• Secondary malignancies, particularly leukemia and other cancers.

Genetic Factors: Unavailable.

Lab Test Interference: Potentially causes transient elevations in liver enzymes; monitor liver function.

Overdose Management

Signs/Symptoms: Severe myelosuppression, nausea, vomiting, hypotension, seizures, coma.

Treatment: Supportive care, including IV fluids, hematopoietic growth factors, blood transfusions, and symptomatic treatment; no specific antidote.

Storage and Handling

Storage: Store at room temperature, protected from light.

Stability: Stable for 24 months when stored properly.