Daunorubicin

Indications

Daunorubicin is used for: Acute leukaemia, AIDS-related Kaposi's sarcoma

Adult Dose

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 Acute Lymphocytic Leukemia 45 mg/m² IVP days 1, 2, 3 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

Child Dose

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 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

Renal Dose

Renal Impairment >3 mg/dL serum creatinine: Administer 50% regular dose

Administration

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4 mL SWI to a final concentration of 5 mg/mL IV Administration Vesicant, never administer IM or SC IVP: desired dose is withdrawn into a syringe containing 10-15 mL NS, then injected over 2-3 min into the tubing or sidearm of a freely flowing IV infusion of NS or D5W Has also been diluted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

Contra Indications

Heart failure. Pregnancy, lactation.

Precautions

Regular blood count and ECG monitoring; elderly, children. Hepatic or renal impairment may increase risk of toxicity. Pre-existing cardiac disease and previous treatment with doxorubicin. Myocardial toxicity leading to potentially fatal congestive heart failure may occur during therapy or mth to yr after therapy cessation. Incidence of myocardial toxicity increases after total cumulative dose exceeds 400-550 mg/m2 in adults, 300 mg/m2 in children >2 yr, or 10 mg/kg in children <2 yr. Risk of severe myelosuppression leading to infection or haemorrhage. Lactation: excretion in milk unknown/not recommended

Pregnancy-Lactation

Pregnancy Category: D Lactation: excretion in milk unknown/not recommended

Interactions

Increased risk of cardiotoxicity when used with cyclophosphamide. Increased risk of hepatic toxicity when used with hepatotoxic drugs e.g. high-dose methotrexate. Potentially Fatal: Immunisation with live vaccines is not recommended. Concurrent radiation may lead to increased radiation reaction.

Adverse Effects

Side effects of Daunorubicin : >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 Potentially Fatal: Bone marrow suppression, cardiac toxicity, cardiomyopathy and congestive heart failure.

Mechanism of Action

Daunorubicin forms a stable complex with DNA and interferes with the nucleic acid synthesis. It is a cell-cycle nonspecific agent, but its cytotoxic effects are mostly marked in the S-phase. It also has immunosuppressant and antibacterial effects.