No

Antineoplastic Agent, Antibiotic

Treatment of ANLL and myeloblastic leukemia; lymphoma

D

Congestive heart failure, cardiopathy or arrhythmias; hypersensitivity to daunorubicin or any component

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. I.V. use only, severe local tissue necrosis will result if extravasation occurs; reduce dose in patients with impaired hepatic, renal, or biliary function; severe myelosuppression is possible when used in therapeutic doses. Total cumulative dose should take into account previous or concomitant treatment with cardiotoxic agents or irradiation of chest.

550 mg/m² in adults

400 mg/m² in patients receiving chest radiation

300 mg/m² in children >2 years of age or

10 mg/kg in children <2 years; this may occur during therapy or several months after therapy

>10%:

Dermatologic: Alopecia (reversible)

Gastrointestinal: Mild nausea or vomiting occurs in 50% of patients within the first 24 hours; stomatitis may occur 3-7 days after administration, but is not as severe as that caused by doxorubicin

Time course for nausea/vomiting: Onset: 1-3 hours; Duration 4-24 hours

Genitourinary: Discoloration of urine (red)

1% to 10%:

Cardiovascular: Congestive heart failure; maximum lifetime dose: Refer to Warnings/Precautions

Extravasation: Daunorubicin is a vesicant; infiltration can cause severe inflammation, tissue necrosis, and ulceration; if the drug is infiltrated, consult institutional policy, apply ice to the area, and elevate the limb

Vesicant chemotherapy

Endocrine & metabolic: Hyperuricemia

Gastrointestinal: GI ulceration, diarrhea

Hematologic: Myelosuppressive: Dose-limiting toxicity; occurs in all patients; leukopenia is more significant than thrombocytopenia

WBC: Severe

Platelets: Severe

Onset (days): 7

Nadir (days): 14

Recovery (days): 21-28

<1%: Pericarditis; myocarditis; chills; skin rash; pigmentation of nail beds; urticaria; elevated serum bilirubin, AST, and alkaline phosphatase; fertility impairment

Symptoms of overdose include myelosuppression, nausea, vomiting, stomatitis

There are no known antidotes; treatment is primarily symptomatic and supportive

Patients may experience impaired immune response to vaccines; possible infection after administration of live vaccines in patients receiving immunosuppressants

Store intact vials at room temperature and protect from light

Dilute vials with 4 mL SWI for a final concentration of 5 mg/mL; reconstituted solution is stable for 4 days at 15°C to 25°C

Protect from fluorescent light to decrease photo-inactivation after storage in solution for several days; protect from direct sunlight

Decomposed drug turns purple

For I.V. push administration, desired dose is withdrawn into a syringe containing 10-15 mL NS

Further dilution in D₅W, LR, or NS is stable for 24 hours at room temperature (25°C) and up to 4 weeks if protected from light

Incompatible with dexamethasone, heparin, sodium bicarbonate, 5-FU

Standard I.V. dilution:

I.V. push: Dose/syringe (initial concentration is 5 mg/mL; however, qs to 10-15 mL with NS)

Maximum syringe size for IVP is a 30 mL syringe and syringe should be <75% full

IVPB: Dose/50-100 mL NS or D₅W

Stable for 24 hours at room temperature (25°C)

Inhibition of DNA and RNA synthesis, by intercalating between DNA base pairs and by steric obstruction; is not cell cycle-specific for the S phase of cell division; daunomycin is preferred over doxorubicin for the treatment of ANLL because of its dose-limiting toxicity (myelosuppression) is not of concern in the therapy of this disease; has less mucositis associated with its use

Distribution: V_d: 40 L/kg; crosses the placenta; distributed to many body tissues, particularly the liver, kidneys, lung, spleen, and heart; does not distribute into the CNS

Metabolism: Primarily in the liver to daunorubicinol (active), which circulates

Half-life: Distribution: 2 minutes; Elimination: 14-20 hours; Terminal: 18.5 hours; Daunorubicinol plasma half-life: 24-48 hours

Elimination: 40% of dose excreted in the bile; ~25% is excreted in the urine as metabolite and unchanged drug; can turn the urine red during first 24-48 hours after treatment

I.V. (refer to individual protocols):

ALL combination therapy: Remission induction: 25-45 mg/m² on day 1 every week for 4 cycles or 30-45 mg/m²/day for 3 days

AML combination therapy: Induction: I.V. continuous infusion: 30-60 mg/m²/day on days 1-3 of cycle

Note: In children <2 years or <0.5 m², daunorubicin should be based on weight - mg/kg: 1 mg/kg per protocol with frequency dependent on regimen employed

Cumulative dose should not exceed 300 mg/m² in children >2 years or 10 mg/kg in children <2 years

Adults:

30-60 mg/m²/day for 3-5 days, repeat dose in 3-4 weeks

AML: Single agent induction: 60 mg/m²/day for 3 days; repeat every 3-4 weeks

AML: Combination therapy induction: 45 mg/m²/day for 3 days of the first course of induction therapy; subsequent courses: Every day for 2 days

ALL combination therapy: 45 mg/m²/day for 3 days

Cumulative dose should not exceed 400-600 mg/m²

Dosing adjustment in renal impairment:

Cl_cr <10 mL/minute: Administer 75% of normal dose

S_cr >3 mg/dL: Administer 50% of normal dose

Dosing adjustment in hepatic impairment:

Serum bilirubin 1.2-3 mg/dL or AST 60-180 int. units: Reduce dose to 75%

Serum bilirubin 3.1-5 mg/dL or AST >180 int. units: Reduce dose to 50%

Serum bilirubin >5 mg/dL: Omit use

CBC with differential and platelet count, liver function test, EKG, ventricular ejection fraction, renal function test

None reported

May produce myelosuppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication can only be administered I.V. During therapy, do not use alcohol, aspirin-containing products, and OTC medications without consulting prescriber. It is important to maintain adequate nutrition and hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) during therapy; frequent small meals may help. You may experience nausea or vomiting (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help). You may experience loss of hair (reversible); you will be more susceptible to infection (avoid crowds and exposure to infection as much as possible). Urine may turn red-pink (normal). Yogurt or buttermilk may help reduce diarrhea (if unresolved, contact prescriber for medication relief). Report fever, chills, unusual bruising or bleeding, signs of infection, abdominal pain or blood in stools, excessive fatigue, yellowing of eyes or skin, swelling of extremities, difficulty breathing, or unresolved diarrhea. Pregnancy/breast-feeding precautions: Do not get pregnant or cause a pregnancy (males) while taking this medication; use appropriate barrier contraceptive measures during and for 1 month following therapy. Breast-feeding is not recommended.

Daunorubicin is a vesicant and should never be administered I.M. or S.C.

Apply ice immediately for 30-60 minutes; then alternate off/on every 15 minutes for one day

Topical cooling may be achieved using ice packs or cooling pad with circulating ice water; cooling of site for 24 hours as tolerated by the patient. Elevate and rest extremity 24-48 hours, then resume normal activity as tolerated. Application of cold inhibits vesicant's cytotoxicity.

Application of heat or sodium bicarbonate can be harmful and is contraindicated

If pain, erythema, and/or swelling persist beyond 48 hours, refer patient immediately to plastic surgeon for consultation and possible debridement

Powder for injection, lyophilized: 20 mg

Bassan R, Lerede T, Rambaldi A, et al, "Role of Anthracyclines in the Treatment of Adult Acute Lymphoblastic Leukemia," Acta Haematol, 1996, 95(3-4):188-92.

Crom WR, Glynn-Barnhart AM, Rodman JH, et al, "Pharmacokinetics of Anticancer Drugs in Children," Clin Pharmacokinet, 1987, 12(3):168-213.

Cuttner J, Mick R, Budman DR, et al, "Phase III Trial of Brief Intensive Treatment of Adult Acute Lymphocytic Leukemia Comparing Daunorubicin and Mitoxantrone: A CALGB Study," Leukemia, 1991, 5(5):425-31.

Davis HL and Davis TE, "Daunorubicin and Adriamycin in Cancer Treatment: An Analysis of Their Roles and Limitations," Cancer Treat Rep, 1979, 63(5):809-15.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Masaoka T, Ogawa M, Yamada K, et al, "A Phase II Comparative Study of Idarubicin Plus Cytarabine Versus Daunorubicin Plus Cytarabine in Adult Acute Myeloid Leukemia," Semin Hematol, 1996, 33(4 Suppl 3):12-7.

Weick JK, Kopecky KJ, Appelbaum FR, et al, "A Randomized Investigation of High-Dose Versus Standard-Dose Cytosine Arabinoside With Daunorubicin in Patients With Previously Untreated Acute Myeloid Leukemia: A Southwest Oncology Group Study," Blood, 1996, 88(8):2841-51.