daunorubicin hydrochloride

daw-noe-ROO-bi-sin HYE-dro-KLOR-ide

Therapeutic Classification: antineoplastics

Pharmacologic Classification: anthracyclines

High Alert

Remission induction of various leukemias.

Forms a complex with DNA, which subsequently inhibits DNA and RNA synthesis (cell-cycle phase-nonspecific).

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Extensively metabolized by the liver. Converted partially to a compound that also has antineoplastic activity (daunorubicinol); 40% eliminated by biliary excretion.

Half-Life: Daunorubicin: 18.5 hr. Daunorubicinol: 26.7 hr.

(effects on blood counts)

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)
;
Hepatic impairment (↓ dose)
;
Previous anthracycline therapy or underlying cardiovascular disease (↑ risk of cardiotoxicity);
Rep: Women of reproductive potential;
Geri: ↓dose recommended for patients ≥60 yr.

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

Drug-drug:

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

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 1st course, then for 2 days of 2nd course (as part of combination regimen).
IV (Adults ≥60 yr): 30 mg/m²/day for 3 days in 1st course, then for 2 days of 2nd 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.

Renal Impairment

IV (Adults ):
CCr 30–50 mL/min: Administer 75% of normal dose; CCr <30 mL/min or hemodialysis: Administer 50% of normal dose.

Hepatic Impairment

IV (Adults ):
Serum bilirubin 1.2–3 mg/dL: Administer 75% of normal dose; Serum bilirubin >3 mg/dL: Administer 50% of normal dose.

(Generic available)

Solution for injection: 5 mg/mL

Monitor vital signs before and frequently during therapy.
Monitor for bone marrow suppression. 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 ↑ fatigue, dyspnea, and orthostatic hypotension.
Monitor intake and output, appetite, and nutritional intake. Assess for nausea and vomiting, which, although mild, may persist for 24–48 hr. Administrating 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, JVD) and usually occurs 1–6 mo after initiation of therapy. Obtain chest x-ray, echocardiography, ECGs, and radionuclide angiography determination of left ventricular ejection fraction (LVEF) before each course of therapy and periodically during therapy. A 30% ↓ in QRS voltage and ↓ in LVEF 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 ↑ risk of developing cardiotoxicity. Cardiotoxicity may develop if cumulative dose >400–550 mg/m² in adults, 300 mg/m² in children >2 yr, or 10 mg/kg in children <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 transiently ↑ serum alkaline phosphatase, bilirubin, and AST concentrations.
- Monitor renal function before each course of therapy.

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.
Do not confuse daunorubicin hydrochloride with doxorubicin or idarubicin. To prevent confusion, orders should include generic and brand name.
High Alert:
Administer under supervision of a physician experienced in use of cancer chemotherapeutic agents.
Provide antiemetics before each infusion.

IV Administration:

Daunorubicin is a vesicant. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry cold compresses for 20 min 4 times day for 1–2 days. Initiate antidote (dexrazoxane or topical dimethyl sulfoxide) based on time frame of noting extravasation. If extravasation is noted ≤6 hr of daunorubicin infusion, administer dexrazoxane 1000 mg/m² over 1–2 hr on Days 1 and 2 (max dose = 2000 mg/day), followed by 500 mg/m² over 1–2 hr on Day 3 (max dose = 1000 mg/day). Hold cold compresses 15 min before initiating and after completing dexrazoxane infusion. Concurrent treatment with topical dimethyl sulfoxide should not be used with dexrazoxane because it may ↓ dexrazoxane's effectiveness. If extravasation is noted >6 hr after completion of daunorubicin infusion, apply dimethyl sulfoxide by saturating a gauze pad and painting on an area twice the size of the extravasation. Allow site to air-dry and repeat application every 8 hr for 7 days. Do not cover the area with dressing.
Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
IV Push: Diluent: Dilute appropriate volume of drug solution 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 2–3 min. Rapid administration rate may cause facial flushing or erythema along the vein.
Intermittent Infusion: Diluent: Appropriate volume of drug solution may also be diluted in 50–100 mL of 0.9% NaCl.
Rate: Infuse 50 mL over 10–15 min or 100 mL over 30–45 min.
Y-Site Compatibility:
- alemtuzumab
- amikacin
- amiodarone
- anidulafungin
- argatroban
- arsenic trioxide
- atracurium
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- calcium chloride
- calcium gluconate
- carboplatin
- carmustine
- caspofungin
- chlorpromazine
- ciprofloxacin
- cisatracurium
- cisplatin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- daptomycin
- dexmedetomidine
- dexrazoxane
- digoxin
- diltiazem
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxycycline
- droperidol
- enalaprilat
- ephedrine
- epinephrine
- erythromycin
- esmolol
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- filgrastim
- fluconazole
- gemcitabine
- gemtuzumab ozogamicin
- gentamicin
- glycopyrrolate
- granisetron
- haloperidol
- hydralazine
- hydrocortisone
- hydromorphone
- idarubicin
- imipenem/cilastatin
- insulin regular
- irinotecan
- isoproterenol
- labetalol
- leucovorin
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- melphalan
- meperidine
- meropenem
- methadone
- methotrexate
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- minocycline
- mitomycin
- morphine
- moxifloxacin
- nalbuphine
- naloxone
- nitroglycerin
- norepinephrine
- octreotide
- ondansetron
- oxaliplatin
- paclitaxel
- palonosetron
- pentamidine
- phentolamine
- phenylephrine
- potassium acetate
- potassium chloride
- potassium phosphates
- procainamide
- prochlorperazine
- promethazine
- propranolol
- remifentanil
- rituximab
- sodium acetate
- sodium bicarbonate
- sodium phosphates
- succinylcholine
- sufentanil
- tacrolimus
- theophylline
- thiotepa
- tigecycline
- tobramycin
- topotecan
- trastuzumab
- vancomycin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- acyclovir
- allopurinol
- aminophylline
- amphotericin B deoxycholate
- amphotericin B liposomal
- ampicillin
- ampicillin/sulbactam
- aztreonam
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chloramphenicol
- clindamycin
- dantrolene
- dexamethasone
- diazepam
- ertapenem
- fludarabine
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- heparin
- indomethacin
- ketorolac
- levofloxacin
- methohexital
- methylprednisolone
- mitoxantrone
- nafcillin
- nitroprusside
- pantoprazole
- pemetrexed
- pentobarbital
- phenobarbital
- phenytoin
- piperacillin/tazobactam
- trimethoprim/sulfamethoxazole

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications, especially products containing aspirin or NSAIDs.
Instruct patient to notify health care provider 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.
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 provider immediately if irregular heartbeat, shortness of breath, or swelling of lower extremities occurs.
Discuss possibility of hair loss with patient. 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 provider.
Emphasize the need for periodic lab tests to monitor for side effects.
Rep: May cause fetal harm. Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during therapy and for >4 mo after last dose Advise women to avoid breastfeeding during therapy. May impair fertility.

Death of rapidly replicating cells, particularly malignant ones.

Cerubidine

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Canadian Brand Names ⬆