Adult Dosing
Acute nonlymphocytic leukemia
- <60 yrs
- Daunorubicin 45 mg/m2/day IV x3 days of the first course and on days 1, 2 of subsequent courses with cytosine arabinoside 100 mg/m2/day IV infusion x1 wk for the first course and for 5 days for subsequent courses
60 yrs- Daunorubicin 30 mg/m2/day IV x3 days of the first course and on days 1, 2 of subsequent courses with cytosine arabinoside 100 mg/m2/day IV infusion x1 wk for the first course and for 5 days for subsequent courses
Notes:- Attainment of a normal-appearing bone marrow requires up to 3 courses of induction therapy
- Evaluate bone marrow following recovery from the previous course of induction therapy for determining whether a further course of induction treatment is required
Acute lymphocytic leukemia
- Daunorubicin 45 mg/m2/day IV x3 days with vincristine 2 mg IV on days 1, 8, and 15; prednisone 40 mg/m2/day PO on days 1 through 22, then taper dose between days 22 to 29; L-asparaginase 500 IU/kg/day x10 days IV on days 22 through 32
Acute promyelocytic leukemia [Non-FDA Approved]
- For induction therapy with ATRA (tretinoin) and cytarabine
- Adults < 60 years: 45 mg/m2 IV on days 1-3
- Adults > 60 years: 30 mg/m2 IV on days 1-3
- Note: When using for consolidation therapy also, total dose must not exceed 550mg/m2 because of risk of cumulative cardiotoxicity
Pediatric Dosing
Acute lymphocytic leukemia
- Daunorubicin 25 mg/m2 IV on day 1 of qwk, vincristine 1.5 mg/m2 IV on day 1 of qwk, prednisone 40 mg/m2 PO qd
Notes:- Complete remission will be obtained within 4 such courses of therapy. If after 4 courses the patient is in partial remission provide an additional 1 or if necessary 2 courses in an effort to obtain a complete remission
- Calculate daunorubicin hydrochloride dosage based on weight (1 mg/kg) instead of body surface area in children <2 yrs of age or having <0.5 m2 body surface area
[Outline]
- Bone marrow suppression has occurred in all patients given a therapeutic dose of this drug. Avoid reinitiating of therapy in patients with pre-existing drug-induced bone marrow suppression unless the benefit from such treatment warrants the risk. Superinfection or hemorrhage has occurred on persistent, severe myelosuppression
- Particularly infants and children should be specially observed for potential cardiac toxicity. Pre-existing heart disease and previous therapy with doxorubicin are co-factors of increased risk of daunorubicin-induced cardiac toxicity and the benefit-to-risk ratio of daunorubicin hydrochloride therapy in such patients should be weighed before starting daunorubicin hydrochloride. Rare instances of pericarditis-myocarditis have occurred
- Incidence of drug-induced CHF has increased after exceeding a total cumulative dose of 550 mg/m2. This limit lowered to 400 mg/m2 in patients having received radiation therapy that encompassed the heart. Infants and children are more prone to anthracycline-induced cardiotoxicity compared to that in adults, which is more clearly dose dependent
- Anthracycline therapy (including daunorubicin) in pediatrics is associated with impaired left ventricular systolic performance, reduced contractility, congestive heart failure or death; such conditions have occurred months to years following cessation of chemotherapy. Thoracic irradiation aggravates such conditions. Perform long-term periodic evaluation of cardiac function in such patients
- Consider the total dose of daunorubicin hydrochloride taking into account any previous or concurrent therapy with other potentially cardiotoxic agents or related compounds such as doxorubicin
- Perform an ECG and/or determine systolic ejection fraction before each course of daunorubicin hydrochloride as changes in the ECG and a reduction in the systolic ejection fraction from pre-treatment baseline helps to recognize those patients who are at higher risk for developing CHF. A reduction 30% in limb lead QRS voltage is associated with a significant risk of drug-induced cardiomyopathy. On development of one or the other of these predictive parameters weigh the benefit of continued therapy against the risk of producing cardiac damage
- Prior to administration of this drug evaluate hepatic and renal function using conventional clinical laboratory tests
- This drug is associated with fetal harm when administered to a pregnant woman. Apprised patients about the potential hazard to the fetus if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug. Advise women of childbearing potential to avoid becoming pregnant
- Secondary leukemias have developed in patients exposed to topoisomerase II inhibitors when used in conjunction with other antineoplastic agents or radiation therapy
- Extravasation at the site of IV administration may induce severe local tissue necrosis
- Closely observe patients and frequently determine CBC. Evaluate cardiac, renal, and hepatic function prior to each course of treatment
- Take appropriate measures to control any systemic infection before initiation of therapy
- Therapy is associated with hyperuricemia secondary to rapid lysis of leukemic cells. Initiate allopurinol administration prior to initiating antileukemic therapy. Monitor blood uric acid levels and initiate appropriate therapy in the event that hyperuricemia develops
Cautions: Use cautiously in
- Renal impairment
- Hepatic impairment
- Impaired cardiac function
- Myelosuppression
Pregnancy Category:D
Breastfeeding: Unknown whether this drug is excreted in human milk. Potential for serious adverse reactions in nursing infants exists. Manufacturer recommends discontinuing nursing during therapy.
