daunorubicin hydrochloride

ROUTE	ONSET	PEAK	DURATION
IV	7–10 days	10–14 days	21 days

Contraindicated in:

Hypersensitivity to daunorubicin or any other components in the formulation;
Symptomatic HF or arrhythmias;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Active infections or decreased bone marrow reserve;
Previous radiation therapy (may reactivate skin lesions);
Renal impairment (↓ dose recommended if serum creatinine >3 mg/dL);
Hepatic impairment (↓ dose recommended if serum bilirubin >1.2 mg/dL);
Previous anthracycline therapy or underlying cardiovascular disease (↑ risk of cardiotoxicity);
Rep: Women of reproductive potential;
Geri: dose recommended for patients 60 yr.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmias, CARDIOTOXICITY

Derm: alopecia

EENT: rhinitis, abnormal vision, sinusitis

GI: nausea, vomiting, esophagitis, hepatoxicity, stomatitis

GU: red urine, gonadal suppression

Hemat: anemia, leukopenia, thrombocytopenia

Local: phlebitis at IV site

Metab: hyperuricemia

Misc: chills, fever

Interactions ⬆ ⬇

Drug-drug:

Additive myelosuppression with other antineoplastics.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.
Cyclophosphamide and trastuzumab↑ risk of cardiotoxicity; avoid use of daunorubicin for up to 7 mo after discontinuing trastuzumab.
May ↑ risk of hepatotoxicity with other hepatotoxic agents.

Route/Dosage ⬆ ⬇

In adults, cumulative dose should not exceed 550 mg/m² (450 mg/m² if previous chest radiation)
IV (Adults <60 yr): 45 mg/m²/day for 3 days in first course, then for 2 days of second course (as part of combination regimen).
IV (Adults ≥60 yr): 30 mg/m²/day for 3 days in first course, then for 2 days of second course (as part of combination regimen).
IV (Children >2 yr): 25 mg/m² once weekly (as part of combination regimen). In children <2 yr or BSA <0.5 m², dose should be determined on a mg/kg basis.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 20 mg/vial
Solution for injection: 5 mg/mL

Assessment ⬆ ⬇

Monitor vital signs before 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 taking 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.
Assess IV site frequently for inflammation or infiltration. Instruct patient to notify nurse immediately if pain or irritation at injection site occurs. If extravasation occurs, infusion must be stopped and restarted in another vein to avoid damage to SUBQ tissue. Notify health care professional immediately. Daunorubicin is a vesicant. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush line); remove needle/cannula; elevate extremity. Initiate antidote (dexrazoxane [adult] or dimethyl sulfate [DMSO]). Apply dry cold compresses for 20 min 4 times daily for 1 to 2 days; hold cooling beginning 15 min before dexrazoxane infusion; continue holding cooling until 15 min after infusion is completed. Do not administer topical DMSO in combination with dexrazoxane; may lessen dexrazoxane efficacy.
Monitor intake and output, appetite, and nutritional intake. Assess for nausea and vomiting, which, although mild, may persist for 24–48 hr. Administration of an antiemetic before and periodically during therapy and adjusting diet as tolerated may help maintain fluid and electrolyte balance and nutritional status. Encourage fluid intake of 2000–3000 mL/day. Allopurinol and alkalinization of the urine may be used to help prevent urate stone formation.
Assess for evidence of cardiotoxicity which manifests as HF (peripheral edema, dyspnea, rales/crackles, weight gain, jugular venous distention) and usually occurs 1–6 mo after initiation of therapy. Obtain chest x ray, echocardiography, ECGs, and radionuclide angiography determination of ejection fraction before each course of therapy and periodically during therapy. A 30% decrease in QRS voltage and decrease in systolic ejection fraction are early signs of cardiotoxicity. Patients who receive total cumulative doses >550/mm², who have a history of cardiac disease, or who have received mediastinal radiation are at greater risk of developing cardiotoxicity. Cardiotoxicity may develop if cumulative dose exceeds 400 to 550 mg/m² in adults, 300 mg/m² in children older than 2 yr, or 10 mg/kg in children younger than 2 yr. May be irreversible and fatal, but usually responds to early treatment.

Lab Test Considerations:

Monitor uric acid levels periodically during therapy.
- Monitor CBC and differential before and frequently during therapy. The leukocyte count nadir occurs 10–14 days after administration. Recovery usually occurs within 21 days after administration of daunorubicin.
- Monitor AST, ALT, LDH, and serum bilirubin prior to each course of therapy. May cause transiently ↑ serum alkaline phosphatase, bilirubin, and AST concentrations.
- Monitor renal function before each course of therapy.

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.
Do not confuse daunorubicin hydrochloride with doxorubicin or idarubicin. To prevent confusion, orders should include generic and brand name.
Provide antiemetics before each infusion.

IV Administration:

Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
IV: Reconstitution: Reconstitute each 20 mg with 4 mL of sterile water for injection for a concentration of 5 mg/mL. Shake gently to dissolve. Reconstituted medication is stable for 24 hr if refrigerated. Protect from sunlight.
- Do not use aluminum needles when reconstituting or injecting daunorubicin, as aluminum darkens the solution.
Diluent: Dilute further in 10–15 mL of 0.9% NaCl. Administer IV push through Y-site into free-flowing infusion of 0.9% NaCl or D5W.
Rate: Administer over at least 2–3 min. Rapid administration rate may cause facial flushing or erythema along the vein.
Intermittent Infusion: Diluent: May also be diluted in 50–100 mL of 0.9% NaCl.
Rate: Administer 50 mL over 10–15 min or 100 mL over 30–45 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; 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. Patient should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Stomatitis pain may require management with opioid analgesics. Period of highest risk is 3–7 days after administration of dose.
Instruct patient to notify health care professional immediately if irregular heartbeat, shortness of breath, or swelling of lower extremities occurs.
Discuss with patient possibility of hair loss. Explore methods of coping. Regrowth of hair usually begins within 5 wk after discontinuing therapy.
Inform patient that medication may turn urine reddish color for 1–2 days after administration.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: May cause fetal harm. Advise females of reproductive potential and males with a partner of reproductive potential to use effective contraception during therapy and for at least 4 mo after last dose and to avoid breastfeeding during therapy. Inform patient that daunorubicin may cause irreversible gonadal suppression.
Emphasize the need for periodic lab tests to monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇