DAUNORUBICIN HYDROCHLORIDE
| DAUNORUBICIN HYDROCHLORIDE (daw-noe-roo'bi-sin) Cerubidine DAUNORUBICIN CITRATED LIPOSOMAL DaunoXome Classifications: antineoplastic; antibiotic; anthracycline; Therapeutic: antineoplastic Prototype: Doxorubicin HCl Pregnancy Category: D |
Availability
Daunorubicin HCl: 10 mg, 20 mg, 50 mg, 100 mg lyophilized vials;
Daunorubicin Citrated Liposomal: 2 mg/mL (equivalent to 50 mg daunorubicin base) injection
Action
Cytotoxic and antimitotic anthracycline antibiotic that is cell-cycle specific for S-phase of cell division. Toxic properties preclude its use as an antibiotic. Mechanism of action is due to rapid interaction with the DNA molecule changing its shape, thus resulting in inhibition of DNA, RNA, and protein synthesis.
Therapeutic Effect
Antineoplastic effects against acute leukemias with decreased incidence of cardiotoxicity than doxorubicin.
Uses
To induce remission in acute nonlymphocytic/lymphocytic leukemia, advanced HIV-associated Kaposi's sarcoma.
Unlabeled Uses
Non-Hodgkin's lymphoma.
Contraindications
Severe myelosuppression; immunizations (patient, family), and preexisting cardiac disease unless risk-benefit is evaluated; uncontrolled systemic infection; pregnancy (category D), lactation.
Cautious Use
History of gout, urate calculi, hepatic or renal function impairment; older adult patients with inadequate bone reserve due to age or previous cytotoxic drug therapy, tumor cell infiltration of bone marrow, patient who has received potentially cardiotoxic drugs or related antineoplastics.
Route & Dosage
| Neoplasms Adult: IV <60 y, 45 mg/m2/d on days 1, 2, and 3 of first course then days 1 and 2 of subsequent courses (max: total cumulative dose 500–600 mg/m2); ≥60 y, 30 mg/m2/d on days 1, 2, and 3 of first course then days 1 and 2 of subsequent courses Child: IV As combination therapy, ≥2 y, 25 mg/m2 weekly; <2 y, 1 mg/kg Kaposi's Sarcoma (DaunoXome) Adult: IV 40 mg/m2 over 1 h, repeat q2wk (withhold therapy if granulocyte count <750 cells/mm3) Renal Impairment If serum Cr >3 mg/dL, give 50% of dose. Hepatic Impairment For total bilirubin 1.2–3 mg/dL, give 50% of dose; >3–5 mg/dL, give 25% of dose; >5 mg/dL, omit dose |
Administration
Intravenous
Daunorubicin HCl PREPARE: Direct: ??Reconstitute 20 mg vial with 4 mL sterile water for injection. The concentration of the solution will be 5 mg/mL.??Withdraw dose into syringe containing 10–15 mL normal saline. IV Infusion: Dilute further in 100 mL NS as required. ADMINISTER: Direct: Inject over approximately 3 min into the tubing or side arm of a rapidly flowing IV infusion of D5W or NS. Infusion: Give a single dose over 30–45 min. Specific to DaunoXome PREPARE: IV Infusion: Each vial of DaunoXome contains the equivalent of 50 mg daunorubicin base. Dilute with enough D5W to produce a concentration of 1 mg/1 mL. ADMINISTER: IV Infusion: Give DaunoXome over 60 min. Do not use a filter with DaunoXome. INCOMPATIBILITIES Solution/additive: Dexamethasone, heparin. Y-site: Allopurinol, aztreonam, cefepime, fludarabine, lansoprazole, piperacillin/tazobactam.
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- Store reconstituted solution at room temperature (15°–30° C; 59°–86° F) for 24 h and under refrigeration at 2°–8° C (36°–46° F) for 48 h. Protect from light.
Adverse Effects (≥1%)
Body as a Whole: Fever. CNS: Amnesia, anxiety, ataxia, confusion, hallucinations, emotional lability, tremors. CV: Pericarditis, myocarditis, arrhythmias, peripheral edema, CHF, hypertension, tachycardia. GI: Acute nausea and vomiting (mild), anorexia, stomatitis, mucositis, diarrhea (occasionally) hemorrhage. Urogenital: Dysuria, nocturia, polyuria, dry skin. Hematologic: Bone marrow depression thrombocytopenia, leukopenia, anemia, Skin: Generalized alopecia (reversible), transverse pigmentation of nails, severe cellulitis or tissue necrosis at site of drug extravasation. Endocrine: Hyperuricemia, gonadal suppression.Pharmacokinetics
Distribution: Highest concentrations in spleen, kidneys, liver, lungs, and heart; does not cross blood–brain barrier; crosses placenta. Metabolism: In liver to active metabolite. Elimination: 25% in urine, 40% in bile. Half-Life: 18.5–26.7 h.Nursing Implications
Assessment & Drug Effects
- Monitor for therapeutic effectiveness. a profound suppression of bone marrow is required to induce a complete remission. Nadirs for thrombocytes and leukocytes are usually reached in 10–14 d.
- Monitor serum bilirubin; drug dose needs to be reduced when bilirubin is >1.2 mg/dL.
- Lab tests: Perform Hct, platelet count, total and differential leukocyte count, serum uric acid, chest x-ray, and cardiac, hepatic, and renal function tests prior to and periodically during therapy.
- Monitor BP, temperature, pulse, and respiratory function during treatment.
- Monitor for S&S of acute CHF. It can occur suddenly, especially when total dosage exceeds 550 mg/m2, or in patients with compromised heart function because of previous radiation therapy to heart area.
- Report immediately: Breathlessness, orthopnea, change in pulse and BP parameters. Early clinical diagnosis of drug-induced CHF is essential for successful treatment.
- Report promptly S&S of superinfections including elevation of temperature, chills, upper respiratory tract infection, tachycardia, overgrowth with opportunistic organisms because myelosuppression imposes risk of superimposed infection (see Appendix F).
- Protect patient from contact with persons with infections. The most hazardous period is during nadirs of thrombocytes and leukocytes.
- Control nausea and vomiting (usually mild) by antiemetic therapy.
- Inspect oral membranes daily. Mucositis may occur 3–7 d after drug is administered.
Patient & Family Education
- Note: Loss of hair is probable; recovery is usual in 6–10 wk.
- Use barrier contraceptives during treatment because this drug is teratogenic. Tell your physician immediately if you become pregnant during therapy.
- Note: A transient effect of the drug is to turn urine red on the day of infusion.
Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; 
Canadian drug name; 
Prototype drug