DACARBAZINE

DACARBAZINE (da-kar'ba-zeen) DTIC-Dome Classifications: antineoplastic; alkylating agent; Therapeutic: antineoplastic; alkylating agent Prototype: Cyclophosphamide Pregnancy Category: C

Availability

10 mg/mL injection

Action

Cytotoxic agent with alkylating properties, which is cell-cycle nonspecific. Interferes with DNA replication, RNa transcription, and protein synthesis in rapidly proliferating cells.

Therapeutic Effect

Has carcinogenic, mutagenic, and teratogenic effects with minimal immunosuppressive activity.

Uses

As single agent or in combination with other antineoplastics in treatment of metastatic malignant melanoma, refractory Hodgkin's disease.

Unlabeled Uses

Various sarcomas and malignant glucagonoma.

Contraindications

Hypersensitivity to dacarbazine; severe bone marrow suppression; active infection; lactation; pregnancy (category C).

Cautious Use

Hepatic or renal impairment; previous radiation or chemotherapy.

Route & Dosage

Neoplasms Adult: IV 2–4.5 mg/kg/d for 10 d repeated at 4-wk intervals or 250 mg/m2/d for 5 d repeated at 3-wk intervals Hodgkin's Disease Adult: IV 150 mg/m2/d x 5 d; repeat at 4-wk intervals

Administration

Intravenous IV administration to infants and children: Verify correct IV concentration and rate of infusion with physician. Wear gloves when handling this drug. If solution gets into the eyes, wash them with soap and water immediately, then irrigate with water or isotonic saline. PREPARE: Direct: Reconstitute drug with sterile water for injection to make a solution containing 10 mg/mL dacarbazine (pH 3.0–4.0) by adding 9.9 mL to 100 mg or 19.7 mL to 200 mg.  IV Infusion: Dilute further in 50–250 mL of D5W or NS.   ADMINISTER: Direct: Give by direct IV over 1 min.  IV Infusion (preferred): Infuse IV over 30 min. If possible, avoid using antecubital vein or veins on dorsum of hand or wrist where extravasation could lead to loss of mobility of entire limb. Avoid veins in extremity with compromised venous or lymphatic drainage and veins near joint spaces.   INCOMPATIBILITIES Solution/additive: Allopurinol, heparin, hydrocortisone. Y-site: Allopurinol, cefepime, heparin, piperacillin/tazobactam. Administer dacarbazine only to patients under close supervision because close observation and frequent laboratory studies are required during and after therapy. IV extravasation: Monitor injection site frequently (instruct patient to do so, if able). Give prompt attention to patient's complaint of swelling, stinging, and burning sensation around injection site. Extravasation can occur painlessly and without visual signs. Danger areas for extravasation are dorsum of hand or ankle (especially if peripheral arteriosclerosis is present), joint spaces, and previously irradiated areas. If extravasation is suspected, infusion should be stopped immediately and restarted in another vein. Report to the physician. Prompt institution of local treatment is IMPERATIVE.

• Store reconstituted solution up to 72 h at 4° C (39° F) or at room temperature 15°–30° C (59°–86° F) for up to 8 h. Store diluted reconstituted solution for 24 h at 4° C (39° F) or at room temperature for up to 8 h. Protect from light.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity (erythematosus, urticarial rashes, hepatotoxicity, photosensitivity); facial paresthesia and flushing, flu-like syndrome, myalgia, malaise, anaphylaxis. CNS: Confusion, headache, seizures, blurred vision. GI: Anorexia, nausea, vomiting. Hematologic: Severe leukopenia and thrombocytopenia, mild anemia. Skin: Alopecia. Other: Pain along injected vein.

Pharmacokinetics

Distribution: Localizes primarily in liver. Metabolism: In liver by CYP1A2. Elimination: 35–50% in urine in 6 h. Half-Life: 5 h.

Nursing Implications

Assessment & Drug Effects

• Monitor IV site carefully for extravasation; if suspected, discontinue IV immediately and notify physician.
• Note: Skin damage by dacarbazine can lead to deep necrosis requiring surgical debridement, skin grafting, and even amputation. Older adults, the very young, comatose, and debilitated patients are especially at risk. Other risk factors include establishing an IV line in a vein previously punctured several times and the use of nonplastic catheters.
• Lab tests: Monitor for hematopoietic toxicity that usually appears about 4 wk after first dose. Generally, a leukocyte count of <3000/mm³ and a platelet count of <100,000/mm³ require suspension or cessation of therapy.
• Avoid, if possible, all tests and treatments during platelet nadir requiring needle punctures (e.g., IM). Observe carefully and report evidence of unexplained bleeding.
• Monitor for severe nausea and vomiting (>90% of patients) that begin within 1 h after drug administration and may last for as long as 12 h.
• Check patient's mouth for ulcerative stomatitis prior to the administration of each dose.
• Monitor I&O ratio and pattern and daily temperature. Renal impairment extends the half-life and increases danger of toxicity. Report symptoms of renal dysfunction and even a slight elevation of temperature.

Patient & Family Education

• Learn about all potential adverse drug effects.
• Report flu-like syndrome that may occur during or even a week after treatment is terminated and last 7–21 d. Symptoms frequently recur with successive treatments.
• Avoid prolonged exposure to sunlight or to ultraviolet light during treatment period and for at least 2 wk after last dose. Protect exposed skin with sunscreen lotion (SPF 15) and avoid exposure in midday.
• Report promptly the onset of blurred vision or paresthesia.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug