Names and pronunciation
(da-kar′ba-zeen)
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Drug reference
(da-kar′ba-zeen)
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Func. class.: Antineoplastic alkylating agent
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Chem. class.: Cytotoxic triazine
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Do not confuse: dacarbazine/procarbazine
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ACTION: Alkylates DNA, RNA; inhib- its DNA, RNA synthesis; also responsible for breakage, cross-linking of DNA strands; activity is not cell-cycle–phase specific
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USES: Hodgkin’s disease, malignant melanoma
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Unlabeled uses: Metastatic soft tissue sarcoma in combination with other agents
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CONTRAINDICATIONS: Breast- feeding, hypersensitivity Precautions: Renal disease, infection
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Black Box Warning: Pregnancy first trimester, radiation therapy, hepatic dis- ease, bone marrow suppression, second- ary malignancy, requires an experienced clinician Black Box Warning: Increased: toxic- ity, bone marrow suppression: bone marrow suppressants, radiation, other antineoplastics Increase: adverse reaction, decrease antibody reaction—live virus vaccines, do not use together, complete all needed vaccines ≥2 wk prior to first dose Drug/Lab Test Increase: BUN, AST, ALT Decrease: platelets, WBC, RBC Black Box Warning: Bone marrow suppression: monitor CBC, differential, platelet count weekly; notify prescriber of results, allow blood counts to rise to normal prior to use • Monitor temperature, may indicate be- ginning infection, I&O, for nausea, appetite Black Box Warning: New primary ma- lignancy: assess for new malignancy that may occur with this product • Bleeding: hematuria, guaiac, bruising, petechiae of mucosa or orifices q8hr • Effects of alopecia on body image; discuss feelings about body changes Black Box Warning: Hepatotoxicity: assess for jaundice of skin, sclera; dark urine; clay-colored stools; itchy skin; ab- dominal pain; fever; diarrhea; monitor he- patic studies prior to, during therapy (bili- rubin, AST, ALT, LDH) as needed or monthly • Inflammation of mucosa, breaks in skin • IV site for irritation, redness, pain; if infiltration occurs, use hot packs at site • Hypersensitivity reactions, anaphy- laxis: discontinue product, administer meds for anaphylaxis • Increased fluid intake to 2-3 L/day to prevent urate deposits, calculi formation Black Box Warning: Product must be administered by those experienced in the use of cancer chemotherapy Black Box Warning: Pregnancy/breast- feeding: to notify prescriber if pregnancy is planned or suspected; to use reliable con- traceptives during and for several months after therapy; not to breastfeed, contraindi- cated in first trimester
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SIDE EFFECTS GI: Nausea, anorexia, vomiting, hepa- totoxicity, diarrhea HEMA: Thrombocytopenia, leukopenia, anemia INTEG: Alopecia, dermatitis, pain at injection site, photosensitivity; severe sun reactions (high doses) MISC: Flulike symptoms, malaise, fever, myalgia, hypotension SYST: Anaphylaxis, new primary malignancy
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INTERACTIONS
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DOSAGE AND ROUTES Metastatic malignant melanoma • Adult: IV 2-4.5 mg/kg/day × 10 days or 100-250 mg/m2/day × 5 days; repeat q3-4wk depending on response Hodgkin’s lymphoma • Adult: IV 150 mg/m2/day × 5 days with other agents, repeat q4wk; or 375 mg/m2 on days 1 and 15 when given in combination, repeat q15days Soft tissue sarcoma (unlabeled) • Adult/child: IV 250 mg/m2/day as continuous infusion × 4 days q21days
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Available forms: Powder for injection 100-, 200-, 500-mg vials
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Administer: • Antiemetic 30-60 min prior to giving product to prevent vomiting, nausea; vomiting may subside after several doses, nausea/vomiting may be severe and last several hours • Antibiotics for prophylaxis of infec- tion IV route • Use cytotoxic handling precautions • Clarify all orders, double-check original order; may be fatal if wrong dose is given Direct IV route • After diluting 100 mg/9.9 or 200 mg/19.7 mL of sterile water for injection (10 mg/mL), give by slow direct IV over 2-3 min Intermittent IV INFUSION route • May be further diluted in 50-250 mL D5W or NS for injection, given as an infu- sion over ½-1 hr • Watch for extravasation; stop infusion, notify prescriber, provide treatment as to protocol • Store in light-resistant container in a dry area (vials); reconstituted solutions can be stored at ≤8 hr at room tempera- ture or 3 days refrigerated Y-site compatibilities: Amifostine, anidu- lafungin, atenolol, aztreonam, bivaliru- din, bleomycin, caspofungin, DAPTOmy- cin, dexmedetomidine, DOCEtaxel, DOXOrubicin, ertapenem, etoposide, fenoldopam, filgrastim, fludarabine, gemtuzumab, granisetron, levofloxacin, mechlorethamine, melphalan, nesiritide, octreotide, ondansetron, oxaliplatin, PACLitaxel, palonosetron, pamidronate, quinupristin-dalfopristin, sargramostim, teniposide, thiotepa, tigecycline, tirofi- ban, vinorelbine, voriconazole, zole- dronic acid
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Assess:
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Evaluate: • Therapeutic response: decreased tu- mor size, spread of malignancy
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • That patient should avoid prolonged exposure to sun, wear sunscreen • That hair may be lost during treat- ment; that a wig or hairpiece may make the patient feel better; that new hair may be different in color, texture • To report signs of infection: fever, sore throat, flulike symptoms • To report signs of anemia: fatigue, headache, faintness, SOB, irritability • To report bleeding; to avoid use of razors, commercial mouthwash • To avoid aspirin products or ibuprofen
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PHARMACOKINETICS Metabolized by liver; excreted in urine; half- life 5 hr; onset, peak, duration unknown
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• Adult: IV 2-4.5 mg/kg/day × 10 days or 100-250 mg/m2/day × 5 days; repeat q3-4wk depending on response Hodgkin’s lymphoma
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• Adult: IV 150 mg/m2/day × 5 days with other agents, repeat q4wk; or 375 mg/m2 on days 1 and 15 when given in combination, repeat q15days Soft tissue sarcoma (unlabeled)
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• Adult/child: IV 250 mg/m2/day as continuous infusion × 4 days q21days
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