dacarbazine

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues; probably concentrates in liver; some CNS penetration.

Metabolism/Excretion: 50% metabolized by the liver, 50% excreted unchanged by the kidneys.

Half-Life: 5 hr (↑ in renal and hepatic impairment).

Time/Action Profile ⬆ ⬇

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV (WBCs)	16–20 days	21–25 days	3–5 days
IV (platelets)	unknown	16 days	3–5 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Active infection;
Bone marrow depression;
Renal impairment;
Hepatic impairment;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: alopecia, facial flushing, photosensitivity, rash

Endo: gonadal suppression

GI: anorexia, nausea, vomiting, diarrhea, HEPATIC NECROSIS, hepatic vein thrombosis

Hemat: anemia, leukopenia, thrombocytopenia

Local: pain at IV site, phlebitis at IV site, tissue necrosis

MS: myalgia

Neuro: facial paresthesia, malaise

Misc: ANAPHYLAXIS, fever, flu-like syndrome

Interactions ⬆ ⬇

Drug-drug:

Additive bone marrow depression with other antineoplastics.
Carbamazepine, phenobarbital, and rifampin may ↓ levels and effectiveness.
Amiodarone, ciprofloxacin, fluvoxamine, ketoconazole, ofloxacin, isoniazid, or miconazole may ↑ levels and risk of toxicity.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Route/Dosage ⬆ ⬇

Malignant Melanoma

IV (Adults ): 2–4.5 mg/kg/day for 10 days administered every 4 wk or 250 mg/m²/day for 5 days administered every 3 wk.

Hodgkin's Disease

IV (Adults ): 150 mg/m²/day for 5 days (in combination with other agents) administered every 4 wk or 375 mg/m² (in combination with other agents) administered every 15 days.

Availability ⬆ ⬇

Powder for injection: 100 mg/vial; 200 mg/vial

Assessment ⬆ ⬇

Monitor vital signs prior to and frequently during therapy.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Monitor IV site closely. Dacarbazine is an irritant. Instruct patient to notify health care professional immediately if discomfort at IV site occurs. Discontinue IV immediately if infiltration occurs. Applications of hot packs may relieve pain, burning sensation, and irritation at injection site.
Monitor intake and output, appetite, and nutritional intake. Assess for nausea and vomiting, which may be severe and last 1–12 hr. Administration of an antiemetic prior to and periodically during therapy, restricting oral intake for 4–6 hr prior to administration, and adjusting diet as tolerated may help maintain fluid and electrolyte balance and nutritional status. Nausea usually decreases on subsequent doses.

Lab Test Considerations:

Monitor CBC and differential prior to and periodically throughout therapy. The nadir of thrombocytopenia occurs in 16 days. The nadir of leukopenia occurs in 3–4 wk. Recovery begins in 5 days. Withhold dose and notify physician if platelet count is <100,000/mm³ or leukocyte count is <4000/mm³.
- Monitor for increased AST, ALT, BUN, and serum creatinine. May cause hepatic necrosis.

Implementation ⬆ ⬇

Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.

IV Administration:

Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in designated containers.
Reconstitute each 100-mg and 200-mg vial with 9.9 mL and 19.7 mL, respectively, of sterile water for injection. Solution is colorless or clear yellow. Do not use solution that has turned pink. Concentration: 10 mg/mL. Solution is stable for 8 hr at room temperature and for 72 hr if refrigerated.
Intermittent Infusion: Diluent: Further dilute with up to 250 mL of D5W or 0.9% NaCl. Stable for 24 hr if refrigerated or 8 hr at room temperature.
Rate: Administer over 30–60 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; abdominal pain; yellowing of eyes; or blood in urine, stool, or emesis occur. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Patients should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs; may increase GI irritation.
May cause photosensitivity. Instruct patient to avoid sunlight or wear protective clothing and use sunscreen for 2 days after therapy.
Instruct patient to inform health care professional if flu-like syndrome occurs. Symptoms include fever, myalgia, and general malaise. May occur after several courses of therapy. Usually occurs 1 wk after administration. May persist for 1–3 wk. Acetaminophen may be used for relief of symptoms.
Discuss with patient the possibility of hair loss. Explore coping strategies.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise patient of the need for a nonhormonal method of contraception.
Instruct patient not to receive any vaccinations without advice of health care professional.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇