Dosing and uses of Daunorubicin (Cerubidine)
Adult dosage forms and strengths
injectable solution
- 5mg/mL
powder for injection
- 20mg
Acute Nonlymphocytic Leukemia
In combination with cytarabine 100 mg/m²/day IV for 7 days first course, for 5 days subsequent courses
<60 years old: 45 mg/m² IVP days 1, 2, 3 first course; days 1, 2 subsequent courses
>60 years old: 30 mg/m² IVP days 1, 2, 3 first course; days 1, 2 subsequent courses
Monitor: Cardiac, renal, hepatic function
Acute Lymphocytic Leukemia
45 mg/m² IVP days 1, 2, 3
Monitor: Cardiac, renal, hepatic function
Renal Impairment
>3 mg/dL serum creatinine: Administer 50% regular dose
Hepatic Impairment
< 1.2 mg/dL serum bilirubin: Dose adjustment not necessary
1.2-3 mg/dL serum bilirubin: 75% of regular dose
> 3 mg/dL serum bilirubin: 50% of regular dose
Administration
Limit lifetime dose to <550 mg/m² (including doses of related drugs) to reduce risk of cardiotoxicity (400 mg/m² for patients who received irradiation of cardiac region)
Pediatric dosage forms and strengths
injectable solution
- 5mg/mL
powder for injection
- 20mg
Acute Nonlymphocytic Leukemia
<2 years old or <0.5 m² BSA: 1 mg/kg IVP qWeek
>2 years old or >0.5 m² BSA: 25 mg/m² IVP qWeek
Monitor: Cardiac, renal, hepatic function
Acute Lymphocytic Leukemia
<2 years old or <0.5 m² BSA: 1 mg/kg IVP qWeek
>2 years old or >0.5 m² BSA: 25 mg/m² IVP qWeek
Monitor: Cardiac, renal, hepatic function
Administration
Limit lifetime dose for children 2 years old or older to 300 mg/sq.meter, and for children <2 years old to 10 mg/kg to avoid irreversible cardiotoxicity
Daunorubicin (Cerubidine) adverse (side) effects
>10%
Nausea
Vomiting
Arrhythmias
Discoloration of urine
Alopecia
1-10%
Injection site skin flare
Hyperuricemia
GI ulceration
Diarrhea
<1%
Arrythmia
Cardiomyopathy
Bilirubin increased
Pruritus
Urticaria
Frequency not defined
Fever
CHF
Flushing
Stomatitis
Myelosuppression
Rash
Hyperpigmentation of previously radiated areas
Transverse pigmentation of fingernails and toenails
Fertility impairment
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced leukemia-chemotherapy physician. Physician must be capable of responding rapidly to severe hemorrhagic conditions or overwhelming infection.
Administer daunorubicin into a rapidly flowing IV infusion. Severe local tissue necrosis will result if extravasation occurs. Do not administer IM or SC.
Cumulative dosage that exceeds 400 to 550 mg/m² in adults, 300 mg/m² >2 years of age, or 10 mg/kg in children <2 years of age may result in a severe and potentially fatal myocardial toxicity including congestive heart failure; this may occur during therapy or several months to years after therapy.
Severe myelosuppression that could lead to infection or hemorrahage may occur when used at therapeutic doses
Dosage adjustment recommended in patients with renal or hepatic impairment
Contraindications
Hypersensitivity
Active infection
IM or SC administration (vesicant)
Patients who have received max cumulative dose of daunorubicin or doxorubicin
Patients with preexisting myelosuppression from other drug treatments
Cautions
Risk of severe cardiotoxicity (including CHF) & myelosuppression
Caution in hepatic/renal impairment
Children may be more sensitive to cardiotoxic effects than adults
Avoid pregnancy
Secondary leukemias reported when used in combination with radiation or chemotherapy
Pregnancy and lactation
Pregnancy category: d
Lactation: excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Daunorubicin (Cerubidine)
Mechanism of action
Anthracycline; intercalates between DNA base pairs, impairs topoisomerase II function and subsequently inhibits DNA and RNA replication
Pharmacokinetics
Protein Bound: 50-60%
Half-life: 14-20 hr (parent drug), 24-48 hr (daunorubicinol)
Vd: 20-39.2 L/kg
Metabolism: Hepatic
Metabolites: DaunorubicinoL
Clearance: 17.3 mL/min
Excretion: Feces (40%) & urine (25%)
Administration
IV Incompatibilities
Additive: dexamethasone sodium phosphate, heparin
Y-site: allopurinol, aztreonam, cefepime, fludarabine, piperacillin/tazobactam
IV Compatibilities
Additive: cytarabine/etoposide, hydrocortisone Na-succinate
Y-site: amifostine, etoposide phosphate, filgrastim, gemcitabine, granisetron, melphalan, methotrexate, ondansetron, Na-bicarb, teniposide, thiotepa, vinorelbine
IV Preparation
Reconstitute 20 mg vial with 4 mL SWI to a final concentration of 5 mg/mL
IV Administration
Vesicant, never administer IM or SC
IVP: desired dose is withdrawn into a syringe containing 10-15 mL NS, then injected over 2-3 min into the tubing or sidearm of a freely flowing IV infusion of NS or D5W
Avoid small veins, swollen or edematous extremities, & areas overlying joints & tendons as inj sites
Has also been diluted in 100 mL of D5W or NS & infused over 30-45 min
Flush with 5-10 mL of IV solution before & after drug administration
Extravasation Management
Terminate injection or infusion immediately & aspirate back as much as possible
Apply cold pack w/circulating ice water, ice pack or cryogel pack to extravasation site for 15-20 min QID x 24-48 hr
Elevate site for 48 hr, then resume normal activity
Extravasation of <1-2 mL often heal spontaneously. If >3 mL, ulceration may occur.
Protect site from heat & sunlight
Varied results in studies using 99% DMSO to treat extravasation, follow institutional policy
If pain, erythema, &/or swelling persist beyond 48 hr, refer pt immediately to plastic surgeon for consultation & possible debridement
See also Totect
Storage
Store intact vials at room temp
Protect from light
Reconstituted solution stable for 24 hr at room temp or 48 hr if refrigerated
