Daunorubicin

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

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

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

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mL SWI to a final concentration of 5 mg/mL IV Administration Vesicant, never administer IM or SC IVP: desired dose is withdrawn into a syringe containing 10-15 mL NS, then injected over 2-3 min into the tubing or sidearm of a freely flowing IV infusion of NS or D5W Has also been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

Heart failure. Pregnancy, lactation.

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. 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 Infections should be treated before the start of daunorubicin therapy; if during daunorubicin treatment a patient becomes febrile (regardless of neutrophil count), treatment with broad spectrum antibiotics should be initiated; this drug induces medullary aplasia and leukopenia; it is therefore imperative that patients be protected against infection during period of aplasia Daunorubicin treatment may lead to hyperuricemia as a consequence of tumor lysis syndrome at start of therapy; the increase in uric acid in blood due to leukocyte degradation can be controlled by administering allopurinol and liquids to stimulate urine excretion; exercise caution in patients with renal insufficiency Cases of colitis, enterocolitis and neutropenic enterocolitis (typhlitis) have been observed in patients treated with this drug; treatment discontinuation and prompt appropriate medical management are recommended This drug can cause tissue necrosis, thus great care must be taken to inject the product directly into the vein; when this drug is employed in association with other anticancer agents, the dosage of each should be reduced so as to minimize the total toxic effect Some instances of cardiotoxicity leading to congestive heart failure may be observed when a cumulative dose of 25 mg/kg has been reached; in general, this dose must not be exceeded except in certain desperate cases where 30 mg/kg can be administered Likewise, because of possible cardiotoxicity, the drug must not be administered to patients who exhibit myocardial lesions or to those above 75 years of age; before initiating treatment, physical examination, appropriate x-rays and ECG should be performed and repeated at regular intervals thereafter, particularly when the cumulative dose has reached 15 mg/kg It is also recommended that this drug be employed only as a treatment to induce a remission, and not as maintenance therapy MONITORING PARAMETERS Cardiac monitoring is essential. Regular blood count and ECG monitoring.

Pregnancy This drug crosses the placenta; based on data from animal studies, in utero exposure to daunorubicin may cause fetal harm; outcome data following maternal use of this drug are available Lactation Not known if this drug is present in breast milk; due to potential for serious adverse reactions in breastfed infant, the manufacturer recommends that breastfeeding be discontinued during daunorubicin therapy

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. Contraindicated (0) Serious (17) adenovirus types 4 and 7 live, oral darolutamide eliglustat enasidenib erdafitinib etrasimod influenza virus vaccine quadrivalent, adjuvanted influenza virus vaccine trivalent, adjuvanted lasmiditan leniolisib palifermin ropeginterferon alfa 2b sotorasib tepotinib tofacitinib trastuzumab trastuzumab deruxtecan

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.

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.