Daunorubicin must be given into a rapidly flowing intravenous infusion. It must never be given by the intramuscular or subcutaneous route. Severe local tissue necrosis will occur if there is extravasation during administration.
It is recommended that daunorubicin be administered only by physicians who are experienced in leukemia chemotherapy and in facilities with laboratory and supportive resources adequate to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The physician and institution must be capable of responding rapidly and completely to severe hemorrhagic conditions and/or overwhelming infection.
Severe myelosuppression occurs when used in therapeutic doses; this may lead to infection or hemorrhage.
Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure may occur either during therapy or months to years after termination of therapy. The incidence of myocardial toxicity increases after a total cumulative dose exceeding 400 to 550 mg/m2 in adults, 300 mg/m2 in children older than 2 years of age, or 10 mg/kg in children younger than 2 years of age.
Dosage should be reduced in patients with impaired hepatic function.
Dosage should be reduced in patients with impaired renal function.
Note: Cumulative doses above 550 mg/m2 in adults without risk factors for cardiotoxicity and above 400 mg/m2 in adults receiving chest irradiation are associated with an increased risk of cardiomyopathy. Daunorubicin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
Acute lymphocytic leukemia (off-label dosing unless otherwise specified):
CALGB 8811 regimen: IV: 45 mg/m2 (in patients <60 years of age) or 30 mg/m2 (in patients ≥60 years of age) on days 1, 2, and 3 of induction (Course I; 4 week cycle), in combination with cyclophosphamide, prednisone, vincristine, and asparaginase (Larson 1995).
CCG 1961: Adults ≤21 years of age: IV: Induction: 25 mg/m2 once weekly for 4 weeks (in combination with vincristine, prednisone, and asparaginase) (Nachman 2009).
GRAALL-2003: Adults ≤60 years of age:
Induction: IV: 50 mg/m2 on days 1, 2, and 3 and 30 mg/m2 on days 15 and 16 (in combination with prednisone, vincristine, asparaginase, cyclophosphamide, and G-CSF support) (Huguet 2009).
Late intensification: IV: 30 mg/m2 on days 1, 2, and 3 (in combination with prednisone, vincristine, asparaginase, cyclophosphamide, and G-CSF support) (Huguet 2009).
MRC UKALLXII/ECOG E2993: Adults <60 years of age: Induction (Phase I): IV: 60 mg/m2 on days 1, 8, 15, and 22 (in combination with vincristine, asparaginase, and prednisone) (Rowe 2005).
PETHEMA ALL-96: Adults ≤30 years of age:
Induction: IV: 30 mg/m2 on days 1, 8, 15, and 22 (in combination with vincristine, prednisone, asparaginase, and cyclophosphamide) (Ribera 2008).
Consolidation-2/Reinduction: IV: 30 mg/m2 on days 1, 2, 8, and 9 (in combination with vincristine, dexamethasone, asparaginase, and cyclophosphamide) (Ribera 2008).
Protocol 8707: Adults ≤60 years of age: IV: Induction and Consolidation 2A cycles: 60 mg/m2 on days 1, 2, and 3 (in combination with vincristine, prednisone, and asparaginase). An additional 60 mg/m2 daunorubicin dose may be administered on day 15 of induction if bone marrow biopsy on day 14 shows residual disease (Linker 2002).
Manufacturer's labeling: IV: 45 mg/m2 on days 1, 2, and 3 (in combination with vincristine, prednisone, and asparaginase).
Acute myeloid leukemia (off-label dosing unless otherwise specified): Induction:
CCG 2891: Adults <21 years of age: IV: 20 mg/m2/day continuous infusion on days 0 to 4 and 10 to 14 (in combination with dexamethasone, cytarabine, thioguanine, and etoposide) (Woods 1996).
Adults <60 years of age: IV: 90 mg/m2 on days 1, 2, and 3 (in combination with cytarabine). If residual disease was observed on day 12 to day 14 bone marrow biopsy, 45 mg/m2 for 3 days was administered (in combination with cytarabine) (Fernandez 2009).
Adults <60 years of age: IV: 60 mg/m2 on days 1, 2, and 3 (in combination with cytarabine and cladribine); may repeat if partial remission occurs (Holowiecki 2012).
Adults ≥60 years of age: IV: 45 or 90 mg/m2 on days 1, 2, and 3 (in combination with cytarabine); the escalated 90 mg/m2 dose was associated with increased remission rates and overall survival in the subgroup of patients 60 to 65 years of age as compared to patients >65 years of age (Lowenberg 2009).
Manufacturer's labeling:
Adults <60 years of age: Induction: IV: 45 mg/m2 on days 1, 2, and 3 of the first course of induction therapy; subsequent courses: 45 mg/m2 on days 1 and 2 (in combination with cytarabine).
Adults ≥60 years of age: Induction: IV: 30 mg/m2 on days 1, 2, and 3 of the first course of induction therapy; subsequent courses: 30 mg/m2 on days 1 and 2 (in combination with cytarabine).
Acute promyelocytic leukemia (off-label dosing):
Induction: Adults: IV: 50 mg/m2 on days 3, 4, 5, and 6 (in combination with ATRA and cytarabine) (Powell 2010) or 60 mg/m2 on days 1, 2, and 3 (in combination with ATRA and cytarabine) (Ades 2008).
Consolidation: Adults: IV: 50 mg/m2 on days 1, 2, and 3 for 2 cycles (in combination with ATRA; arsenic trioxide was administered for 2 cycles prior to daunorubicin and ATRA) (Powell 2010) or 60 mg/m2 on days 1, 2, and 3 during cycle 1 of consolidation (in combination with cytarabine), followed by 45 mg/m2 on days 1, 2, and 3 during cycle 2 of consolidation (in combination with cytarabine) (Ades 2008).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The manufacturer's labeling recommends the following adjustment: Scr >3 mg/dL: Administer 50% of normal dose
The following adjustments have also been recommended (Aronoff 2007):
No dosage adjustment necessary.
The manufacturer's labeling recommends the following adjustments:
Serum bilirubin 1.2 to 3 mg/dL: Administer 75% of dose
Serum bilirubin >3 mg/dL: Administer 50% of dose
The following adjustments have also been recommended (Floyd 2006):
Serum bilirubin 1.2 to 3 mg/dL: Administer 75% of dose
Serum bilirubin 3.1 to 5 mg/dL: Administer 50% of dose
Serum bilirubin >5 mg/dL: Avoid use
(For additional information see "Daunorubicin: Pediatric drug information")
Note: Dose, frequency, number of doses, and start date may vary by protocol and treatment phase; refer to individual protocols. In pediatric patients, dosing may be based on either BSA (mg/m2) or weight (mg/kg); use extra caution to verify dosing parameters during calculations.
Daunorubicin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]; POGO [Paw Cho Sing 2019]).
Monitor cumulative anthracycline dose (combined); the risk for cardiomyopathy increases as the cumulative anthracycline dose increases (>250 mg/m2 of doxorubicin isotoxic equivalent dose in pediatric patients <18 years and 550 mg/m2 of doxorubicin isotoxic equivalent dose in patients ≥18 years); also dependent on other/additional risk factors (eg, chest irradiation); interpatient variability exists (eg, some patients may experience left ventricular dysfunction at lower doses). To calculate doxorubicin equivalent dose of daunorubicin, multiply total daunorubicin dose by 0.5 (COG 2018; ESC [Zamorano 2016]).
Acute lymphocytic leukemia, B-cell (B-ALL):
AALL0232 (Larsen 2016): High risk, newly diagnosed:
Children and Adolescents:
Induction: IV: 25 mg/m2/dose once weekly for 4 weeks (in combination with intrathecal cytarabine, vincristine, prednisone/dexamethasone [age-dependent], pegaspargase, and intrathecal methotrexate).
Extended induction: IV: 25 mg/m2/dose once on day 1 (in combination with vincristine, prednisone/dexamethasone [age-dependent], and pegaspargase).
Memorial Sloan Kettering-New York IIB Protocol (Steinherz 1993): High risk, newly diagnosed:
Children and Adolescents:
Induction: IV: 60 mg/m2/day as a continuous infusion over 24 hours on days 0 and 1 for a total dose of 120 mg/m2 (in combination with cyclophosphamide, vincristine, prednisone, pegaspargase, and intrathecal methotrexate).
Maintenance I: IV: 20 mg/m2/day as a continuous infusion over 24 hours on days 40 and 41 for a total dose of 40 mg/m2 (in combination with prednisone, mercaptopurine, cyclophosphamide, methotrexate, vincristine, cytarabine, thioguanine, and intrathecal methotrexate). Repeat for a total of 5 cycles.
GRAALL-2003 (Huguet 2009):
Adolescents ≥15 years:
Induction: IV: 50 mg/m2/dose on days 1, 2, and 3 and 30 mg/m2 on days 15 and 16 (in combination with prednisone, vincristine, asparaginase, cyclophosphamide, and G-CSF support).
Late intensification: IV: 30 mg/m2/dose on days 1, 2, and 3 (in combination with prednisone, vincristine, asparaginase, cyclophosphamide, and G-CSF support).
MRC UKALLXII/ECOG E2993 (Rowe 2005):
Adolescents ≥15 years: Induction (Phase I): IV: 60 mg/m2/dose on days 1, 8, 15, and 22 (in combination with vincristine, asparaginase, and prednisone).
PETHEMA ALL-96 (Ribera 2008):
Adolescents ≥15 years:
Induction: IV: 30 mg/m2/dose on days 1, 8, 15, and 22 (in combination with vincristine, prednisone, asparaginase, and cyclophosphamide).
Consolidation-2/Reinduction: IV: 30 mg/m2/dose on days 1, 2, 8, and 9 (in combination with vincristine, dexamethasone, asparaginase, and cyclophosphamide).
Manufacturer's labeling: Remission induction:
Infants and Children <2 years or BSA <0.5 m2: IV: 1 mg/kg/dose on day 1 every week for up to 4 to 6 cycles (in combination with vincristine and prednisone).
Children and Adolescents ≥2 years and BSA ≥0.5 m2: IV: 25 mg/m2/dose on day 1 every week for up to 4 to 6 cycles (in combination with vincristine and prednisone).
Acute lymphoblastic leukemia, T-cell (T-ALL):
AALL0434 (Winter 2018): Newly diagnosed: Children and Adolescents: Induction: IV: 25 mg/m2/dose on days 1, 8, 15, 22 (in combination with vincristine, prednisone, pegaspargase, intrathecal methotrexate, and cytarabine).
Acute myelogenous leukemia (AML):
AAML0531 (Burnett 2013; Gamis 2014): Newly diagnosed:
Note: Some aspects of protocol dosing based on previous reports (Cooper 2012; Gibson 2011; Guest 2014; Woods 1990).
Infants and Children with BSA <0.6 m2: Induction I and Induction II: IV: 1.67 mg/kg/dose on days 1, 3, 5 (in combination with cytarabine and etoposide).
Children and Adolescents with BSA ≥0.6 m2: Induction I and Induction II: IV: 50 mg/m2/dose on days 1, 3, and 5 (in combination with cytarabine and etoposide).
AAML0431 (Taub 2017): Patients with Down syndrome <4 years of age at time of AML diagnosis:
Infants and Children ≤3 years: Induction I, III, and IV: IV: 0.67 mg/kg/day as a continuous infusion on days 1 to 4 (96 hours total) (in combination with cytarabine and thioguanine).
Children >3 to <4 years: Induction I, III, and IV: IV: 20 mg/m2/day as a continuous infusion on days 1 to 4 (96 hours total) (in combination with cytarabine and thioguanine).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The manufacturer's labeling recommends the following adjustment: All patients: SCr >3 mg/dL: Administer 50% of normal dose.
The following adjustments have also been recommended (Aronoff 2007):
Infants, Children, and Adolescents:
CrCl <30 mL/minute: Administer 50% of dose.
Hemodialysis/continuous ambulatory peritoneal dialysis (CAPD): Administer 50% of dose.
The manufacturer's labeling recommends the following adjustments: All patients:
Serum bilirubin 1.2 to 3 mg/dL: Administer 75% of dose.
Serum bilirubin >3 mg/dL: Administer 50% of dose.
The following adjustments have also been recommended based on experience from adult patients (Floyd 2006): All patients:
Serum bilirubin 1.2 to 3 mg/dL: Administer 75% of dose.
Serum bilirubin 3.1 to 5 mg/dL: Administer 50% of dose.
Serum bilirubin >5 mg/dL: Avoid use.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as hydrochloride:
Generic: 20 mg/4 mL (4 mL)
Solution, Intravenous, as hydrochloride [preservative free]:
Generic: 20 mg/4 mL (4 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
Cerubidine: 20 mg (1 ea)
Generic: 20 mg ([DSC])
Daunorubicin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
IV: For IV administration only. Do not administer IM or SubQ. Administer as slow IV push over 1 to 5 minutes into the tubing of a rapidly infusing IV solution of D5W or NS or may dilute further and infuse over 15 to 30 minutes.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate antidote (dexrazoxane or dimethyl sulfate [DMSO]). Apply dry cold compresses for 20 minutes 4 times daily for 1 to 2 days (Perez Fidalgo 2012); withhold cooling beginning 15 minutes before dexrazoxane infusion; continue withholding cooling until 15 minutes after infusion is completed. Topical DMSO should not be administered in combination with dexrazoxane; may lessen dexrazoxane efficacy.
Dexrazoxane: 1,000 mg/m2 (maximum dose: 2,000 mg) IV (administer in a large vein remote from site of extravasation) over 1 to 2 hours days 1 and 2, then 500 mg/m2 (maximum dose: 1,000 mg) IV over 1 to 2 hours day 3; begin within 6 hours of extravasation. Day 2 and day 3 doses should be administered at approximately the same time (± 3 hours) as the dose on day 1 (Mouridsen 2007; Perez Fidalgo 2012). Note: Reduce dexrazoxane dose by 50% in patients with moderate to severe renal impairment (CrCl <40 mL/minute).
DMSO: Apply topically to a region covering twice the affected area every 8 hours for 7 days; begin within 10 minutes of extravasation; do not cover with a dressing (Perez Fidalgo 2012).
Daunorubicin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]; POGO [Paw Cho Sing 2019]).
Parenteral: Administration rate/technique may vary by protocol. May administer IV push over 1 to 15 minutes into the tubing of a rapidly infusing IV solution of D5W or NS. Some pediatric protocols use a continuous infusion of the daily dose over 24 hours. Drug is very irritating, do not inject IM or SUBQ. Refer to individual protocol for details, particularly if the patient is receiving dexrazoxane as a cardioprotectant (including timing with respect to dexrazoxane administration); take precautions to minimize extravasation risks.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate antidote (dimethyl sulfate [DMSO] or dexrazoxane [adult]) (see Management of Drug Extravasations for more details). Apply dry cold compresses for 20 minutes 4 times daily for 1 to 2 days (Pérez Fidalgo 2012); withhold cooling beginning 15 minutes before dexrazoxane infusion; continue withholding cooling until 15 minutes after infusion is completed. Topical DMSO should not be administered in combination with dexrazoxane; may lessen dexrazoxane efficacy.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Acute lymphocytic leukemia: Treatment (remission induction) of acute lymphocytic leukemia (ALL) in children and adults (in combination with other chemotherapy)
Acute myeloid leukemia: Treatment (remission induction) of acute myeloid leukemia (AML) in adults (in combination with other chemotherapy)
DAUNOrubicin may be confused with DACTINomycin, DAUNOrubicin liposomal, DOXOrubicin, DOXOrubicin liposomal, epiRUBicin, IDArubicin, valrubicin
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
>10%:
Cardiovascular: Cardiac failure (dose-related, may be delayed for 7 to 8 years after treatment), ECG abnormality (transient, generally asymptomatic and self-limiting; includes atrial premature contractions, ST segment changes on ECG, supraventricular tachycardia, ventricular premature contractions)
Dermatologic: Alopecia (reversible)
Gastrointestinal: Nausea (mild), stomatitis, vomiting (mild)
Genitourinary: Red urine discoloration
Hematologic & oncologic: Bone marrow depression (onset: 7 days; nadir: 10 to 14 days; recovery: 21 to 28 days; primarily leukopenia; anemia, thrombocytopenia)
Miscellaneous: Radiation recall phenomenon
1% to 10%:
Dermatologic: Discoloration of sweat
Endocrine & metabolic: Hyperuricemia
Gastrointestinal: Abdominal pain, diarrhea, discoloration of saliva, gastrointestinal ulcer
Local: Post-injection flare
Ophthalmic: Discoloration of tears
<1%, postmarketing, and/or case reports: Anaphylactoid reaction, cardiac arrhythmia, cardiomyopathy, hepatitis, hypersensitivity reaction (systemic; includes angioedema, dysphagia, dyspnea, pruritus, urticaria), increased serum bilirubin, increased serum transaminases, infertility, injection site reaction (includes injection site cellulitis, local thrombophlebitis, pain at injection site), leukemia (secondary), myocardial infarction, myocarditis, nail bed changes (pigmentation), nail disease (banding), onycholysis, pericarditis, skin rash, sterility, typhlitis (neutropenic)
Hypersensitivity to daunorubicin or any component of the formulation
Canadian labeling: Patients who exhibit myocardial lesions or those ≥75 years of age
Concerns related to adverse effects:
• Bone marrow suppression: [US Boxed Warning]: May cause severe bone marrow suppression when used at therapeutic doses; may lead to infection or hemorrhage. Use with caution in patients with drug-induced bone marrow suppression (preexisting), unless the therapy benefit outweighs the toxicity risk. Monitor blood counts at baseline and frequently during therapy.
• Extravasation: [US Boxed Warning]: Vesicant; if extravasation occurs, severe local tissue damage leading to ulceration and necrosis, and pain may occur. For IV administration only. NOT for IM or SubQ administration. Administer through a rapidly flowing IV line. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
• Cardiomyopathy: [US Boxed Warning]: May cause cumulative, dose-related myocardial toxicity; may lead to heart failure. May occur either during treatment or may be delayed (months to years after cessations of treatment). The incidence of myocardial toxicity increases as the total cumulative (lifetime) dosages approach 550 mg/m2 in adults, 400 mg/m2 in adults receiving chest radiation, 300 mg/m2 in children >2 years of age, or 10 mg/kg in children <2 years of age. Total cumulative dose should take into account prior treatment with other anthracyclines or anthracenediones, previous or concomitant treatment with other cardiotoxic agents or irradiation of chest. Although the risk increases with cumulative dose, irreversible cardiotoxicity may occur at any dose level. Patients with preexisting heart disease, hypertension, concurrent administration of other antineoplastic agents, prior or concurrent chest irradiation, advanced age; and infants and children are at increased risk. Monitor left ventricular (LV) function (baseline and periodic) with ECHO or MUGA scan; monitor ECG.
ASCO has developed guidelines for prevention and monitoring of cardiac dysfunction in adult survivors of cancer (ASCO [Armenian 2017]). According to the guidelines, the risk of cardiac dysfunction is increased with the following:
• High-dose anthracycline therapy (eg, doxorubicin ≥250 mg/m2, epirubicin ≥600 mg/m2)
• High-dose radiotherapy (≥30 Gy) with the heart in the treatment field
• Lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) in combination with lower-dose radiotherapy (<30 Gy) with the heart in the treatment field
• Lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) or trastuzumab alone AND any of the following risk factors: Multiple cardiovascular risk factors (≥2 risk factors), including smoking, hypertension, diabetes, dyslipidemia, and obesity (during or after completion of therapy), or older age (≥60 years of age) at cancer treatment, or compromised cardiac function (eg, borderline low LVEF [50% to 55%], history of MI, moderate or higher valvular heart disease) before or during treatment
• Treatment with lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) followed by trastuzumab (sequential therapy)
• Other risk factors for anthracycline-induced cardiotoxicity include ≥60 years of age at time of treatment and ≥2 cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, or obesity) during or after treatment.
The ASCO guidelines recommend a comprehensive assessment in patients with cancer that includes a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking. An echocardiogram should be obtained prior to initiating potentially cardiotoxic therapies. Modifiable risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) should be actively managed before initiating potentially cardiotoxic therapies. Consider cardioprotectants (eg, dexrazoxane) or continuous infusions in patients who are likely to receive high-dose anthracycline therapy. In patients who develop signs/symptoms of cardiac dysfunction during therapy, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or MUGA scan may be utilized. Serum cardiac biomarkers are recommended, along with referral to a cardiologist if indicated.
• Secondary malignancy: Secondary leukemias may occur when used with combination chemotherapy or radiation therapy.
• Tumor lysis syndrome: May cause tumor lysis syndrome and hyperuricemia. Urinary alkalinization and prophylaxis with an antihyperuricemic agent may be necessary. Monitor electrolytes, renal function, and hydration status.
Disease-related concerns:
• Hepatic impairment: [US Boxed Warning]: Dosage reductions are recommended in patients with hepatic impairment; significant hepatic impairment may result in increased toxicities.
• Renal impairment: [US Boxed Warning]: Dosage reductions are recommended in patients with renal impairment; significant renal impairment may result in increased toxicities.
Special populations:
• Elderly: Cardiotoxicity may occur more frequently in elderly patients. Use with caution in patients with impaired renal function and/or poor marrow reserve due to advanced age; dosage adjustment may be necessary.
• Pediatric: Infants and children are at increased risk for developing delayed cardiotoxicity; long-term periodic cardiac function monitoring is recommended. A panel from the American Society of Pediatric Hematology/Oncology (ASPHO) and International Society of Pediatric Oncology (SIOP) recommends in favor of an anthracycline infusion duration of at least 1 hour in pediatric patients to reduce the potential for cardiotoxicity (ASPHO/SIOP [Loeffen 2018]). However, extravasation risks should also be minimized and the protocol infusion duration specified in a protocol should be followed, particularly if the patient is receiving dexrazoxane as a cardioprotectant.
• Radiation recipients: Use with caution in patients who have received radiation therapy; reduce dosage in patients who are receiving radiation therapy simultaneously.
Dosage form specific issues:
• Formulations (conventional vs liposomal): Use caution when selecting product for preparation and dispensing; indications, dosages, and adverse event profiles differ between conventional daunorubicin hydrochloride solution and daunorubicin liposomal.
Other warnings/precautions:
• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
Pediatric patients are at increased risk for developing delayed cardiac toxicity and congestive heart failure during early adulthood due to an increasing census of long-term survivors; risk factors include: Young treatment age (<5 years), cumulative exposure, and concomitant cardiotoxic therapy. Up to 40% of pediatric patients may have subclinical cardiac dysfunction and 5% to 10% may develop heart failure. Long-term monitoring is recommended for all pediatric patients (COG 2018).
Substrate of P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Ado-Trastuzumab Emtansine: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with ado-trastuzumab emtansine should avoid anthracycline-based therapy for up to 7 months after stopping ado-trastuzumab emtansine. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider therapy modification
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Bevacizumab: May enhance the cardiotoxic effect of Anthracyclines. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cardiac Glycosides: May diminish the cardiotoxic effect of Anthracyclines. Anthracyclines may decrease the serum concentration of Cardiac Glycosides. The effects of liposomal formulations may be unique from those of the free drug, as liposomal formulation have unique drug disposition and toxicity profiles, and liposomes themselves may alter digoxin absorption/distribution. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Risk C: Monitor therapy
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Cyclophosphamide: May enhance the cardiotoxic effect of Anthracyclines. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fam-Trastuzumab Deruxtecan: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with fam-trastuzumab deruxtecan should avoid anthracycline-based therapy for up to 7 months after stopping fam-trastuzumab deruxtecan. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Margetuximab: Anthracyclines may enhance the adverse/toxic effect of Margetuximab. Specifically, the risk of cardiac dysfunction may be increased. Management: Avoid anthracycline-based therapy for up to 4 months after discontinuing margetuximab due to an increased risk of cardiac dysfunction. If anthracyclines must be used with margetuximab monitor cardiac function closely. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taxane Derivatives: May enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Management: Consider separating doxorubicin and paclitaxel administration by as much time as possible, using liposomal doxorubicin or epirubicin instead of doxorubicin, or using docetaxel instead of paclitaxel. Monitor closely for cardiovascular and other toxicities. Risk D: Consider therapy modification
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Trastuzumab: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab. Risk D: Consider therapy modification
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Women of reproductive potential should avoid pregnancy.
Daunorubicin crosses the placenta. Based on data from animal reproduction studies, in utero exposure to daunorubicin may cause fetal harm.
It is not known if daunorubicin is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends that breastfeeding be discontinued during daunorubicin therapy.
CBC with differential and platelet count, liver function test, ECG, left ventricular ejection function (echocardiography [ECHO] or multigated radionuclide angiography [MUGA] scan), renal function tests. Monitor for signs/symptoms of extravasation.
Cardiovascular monitoring (ASCO [Armenian 2017]): Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking. Echocardiogram (prior to treatment). In patients who develop signs/symptoms of cardiac dysfunction during therapy, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or MUGA scan may be utilized; obtain serum cardiac biomarkers.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Daunorubicin inhibits DNA and RNA synthesis by intercalation between DNA base pairs and by steric obstruction. Daunomycin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA.
Distribution: Distributes widely into tissues, particularly the liver, kidneys, lung, spleen, and heart; does not distribute into the CNS
Metabolism: Primarily hepatic to daunorubicinol (active), then to inactive aglycones, conjugated sulfates, and glucuronides
Half-life elimination: Initial: 45 minutes; Terminal: 18.5 hours; Daunorubicinol plasma half-life: ~27 hours
Excretion: Feces (40%); urine (~25% as unchanged drug and metabolites)
Solution (DAUNOrubicin HCl Intravenous)
20 mg/4 mL (per mL): $40.24
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