DTIC-Dome

dacarbazine

DTIC, DTIC-Dome

FDA Box Warning

Give under supervision of physician experienced in cancer chemotherapy.

Hematopoietic depression is most common toxicity; hepatic necrosis has also occurred.

Drug is carcinogenic and teratogenic in animals.

Prescriber must weigh potential benefit against toxicity risk.

Action

Unclear. Thought to inhibit DNA synthesis by acting as purine analog. Also causes alkylation and may interact with sulfhydryl groups.

Availability

Injection: 100-mg and 200-mg vials

Indications and dosages

➣ Hodgkin's disease

Adults: 150 mg/m2 I.V. daily for 5 days in combination with other drugs, repeated q 4 weeks. Or 375 mg/m2 I.V. on first day of combination therapy, repeated q 15 days.

➣ Metastatic malignant melanoma

Adults: 2 to 4.5 mg/kg I.V. daily for 10 days, repeated q 4 weeks. Or 250 mg/m2 I.V. daily for 5 days, repeated q 3 weeks.

Off-label uses

• Malignant pheochromocytoma

Contraindications

• Hypersensitivity to drug

Precautions

Use cautiously in:

• hepatic dysfunction, impaired bone marrow function

• pregnant or breastfeeding patients

• children.

Administration

• Follow facility procedures for safe handling, administration, and disposal of chemotherapeutic drugs.

• Reconstitute with sterile water for injection according to manufacturer's directions.

• Further dilute reconstituted drug with 5% dextrose in water or normal saline solution.

Administer over 30 to 60 minutes by I.V. infusion only.

Take steps to prevent extravasation, which may cause tissue damage and severe pain.

Adverse reactions

CNS: malaise, paresthesia

GI: nausea, vomiting, dyspepsia, anorexia

Hematologic: anemia, leukopenia, thrombocytopenia, bone marrow depression

Musculoskeletal: myalgia

Skin: dermatitis, erythematous or urticarial rash, alopecia, flushing, photosensitivity

Others: flulike symptoms, fever, hypersensitivity reactions including anaphylaxis

Interactions

Drug-diagnostic tests. Platelets, red blood cells, white blood cells: decreased counts

Drug-behaviors. Sun exposure: photosensitivity reaction

Patient monitoring

Frequently monitor CBC with white cell differential and platelet count. Know that hematopoietic depression is the most common toxicity and can be fatal.

• Assess infusion site closely for extravasation.

Patient teaching

Instruct patient to immediately report pain, burning, or swelling at infusion site; numbness in arms or legs; gait changes; respiratory distress; difficulty breathing; rash; or easy bruising or bleeding.

• Advise patient to minimize GI distress by eating small, frequent servings of healthy food and drinking plenty of fluids.

• Tell patient he'll undergo regular blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests and behaviors mentioned above.

dacarbazine

(da-kar-ba-zeen) dacarbazine,

DTIC

(trade name),

DTIC-Dome

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: alkylating agents
Pregnancy Category: C

Indications

Treatment of metastatic malignant melanoma (single agent).Treatment of Hodgkin’s disease as second-line therapy (with other agents).

Action

Disrupts DNA and RNA synthesis (cell-cycle phase–nonspecific).

Therapeutic effects

Death of rapidly growing tissue cells, especially malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.Distribution: Large volume of distribution; probably concentrates in liver; some CNS penetration.Metabolism and Excretion: 50% metabolized by the liver, 50% excreted unchanged by the kidneys.Half-life: 5 hr (↑ in renal and hepatic dysfunction).

Time/action profile (effects on blood counts)

ROUTEONSETPEAKDURATION
IV (WBCs)16–20 days21–25 days3–5 days
IV (platelets)unknown16 days3–5 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Obstetric / Lactation: Pregnancy or lactation.Use Cautiously in: Active infections;Bone marrow depression; Pediatric: Children (safety not established);Renal dysfunction;Hepatic dysfunction.

Adverse Reactions/Side Effects

Gastrointestinal

  • hepatic necrosis (life-threatening)
  • anorexia (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • diarrhea
  • hepatic vein thrombosis

Dermatologic

  • alopecia
  • facial flushing
  • photosensitivity
  • rash

Endocrinologic

  • gonadal suppression

Hematologic

  • anemia (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)

Local

  • pain at IV site (most frequent)
  • phlebitis at IV site
  • tissue necrosis

Musculoskeletal

  • myalgia

Neurologic

  • facial paresthesia

Miscellaneous

  • anaphylaxis (life-threatening)
  • fever
  • flu-like syndrome
  • malaise

Interactions

Drug-Drug interaction

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

Route/Dosage

Other regimens are usedIntravenous (Adults) Malignant melanoma—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—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: 200 mg

Nursing implications

Nursing 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.

Potential Nursing Diagnoses

Risk for infection (Side Effects)
Risk for injury (Side Effects)

Implementation

  • high alert: 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.
  • Intravenous Administration
  • pH: 3.0–4.0.
  • Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in designated containers (see ).
  • Reconstitute each 200-mg vial with 19.7 mL 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.
  • Y-Site Compatibility: amifostine, aztreonam, bivalirudin, caspofungin, daptomycin, dexmedetomidine, docetaxel, doxorubicin liposome, ertapenem, etoposide phosphate, fenoldopam, filgrastim, fludarabine, granisetron, hetastarch, levofloxacin, mechlorethamine, melphalan, nesiritide, octreotide, ondansetron, oxaliplatin, paclitaxel, palonosetron, quinupristin/dalfopristin, sargramostim, teniposide, thiotepa, tigecycline, tirofiban, vinorelbine, voriconazole
  • Y-Site Incompatibility: allopurinol, amphotericin B liposome, cefepime, pantoprazole, pemetrexed, piperacillin/tazobactam

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 occurs. 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.
  • Advise patient of the need for a nonhormonal method of contraception.
  • Instruct patient not to receive any vaccinations without advice of health care professional.

Evaluation/Desired Outcomes

  • Decrease in size and spread of malignant melanoma or Hodgkin’s lymphoma.

DTIC-Dome

A brand name for DACARBAZINE.