Daunorubicin

Uses

Daunorubicin in combination with other approved anticancer drugs is used for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.

Daunorubicin is also used to associated treatment for these conditions: Acute Lymphocytic Leukemia (ALL), Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia With Myelodysplasia-Related Changes, Acute erythroid leukemia, Acute monocytic leukaemia, Newly diagnosed Therapy-Related Acute Myeloid Leukemia

How Daunorubicin works

Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

Dosage

Daunorubicin dosage

Intravenous-

Acute leukaemias:

• Adult:30-45 mg/m2BSA daily on days 1-3 of the induction course and days 1 and 2 for the subsequent courses. Admin as a solution in 0.9% sodium chloride into a fast-running infusion of sodium chloride or glucose. May repeat course 3-6 wk later. Max (total cumulative dose): 550 mg/m2in patients without risk factors for cardiotoxicity and 400 mg/m2in patients who have received chest radiotherapy.
• Child:For acute lymphoblastic leukaemia: 25 mg/m2BSA once wkly in combination with other regimens. <2 yr old or BSA <0.5 m2: 1 mg/kg once wkly. Max (total cumulative dose): 300 mg/m2and in children <2 yr: 10 mg/kg.

AIDS-related Kaposi's sarcoma:

• Adult:As the liposomal formulation: Initially, 40 mg/m2once every 2 wk, diluted in glucose 5% to a concentration of 0.2-1 mg/ml and given over 30-60 minutes. May continue for as long as disease control can be maintained.

Side Effects

GI disturbances; stomatitis; alopoecia and dermatological reactions. Extravasation of daunorubicin may cause severe local tissue necrosis damaging surrounding muscles, tendons and nerves. IV infusion, back pain, flushing and chest tightness.

Toxicity

LD₅₀=20 mg/kg (mice, IV); LD₅₀=13 mg/kg (rat, IV)

Precaution

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/m2in 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.

Interaction

Increased risk of cardiotoxicity when used with cyclophosphamide. Increased risk of hepatic toxicity when used with hepatotoxic drugs e.g. high-dose methotrexate.

Food Interaction

Daunorubicin Drug Interaction

Moderate: diltiazem, diltiazemMinor: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprimUnknown: RHO Immunoglobulin , RHO Immunoglobulin , diphenhydramine, diphenhydramine, meperidine, meperidine, dexamethasone, dexamethasone, glucose, glucose, metoprolol, metoprolol, metoprolol, metoprolol, acetaminophen, acetaminophen

Daunorubicin Disease Interaction

Major: congestive heart failure, infections, myelosuppressionModerate: hepatic dysfunction, renal dysfunction

Half Life

18.5 hours

Elimination Route

Twenty-five percent of an administered dose of daunorubicin hydrochloride is eliminated in an active form by urinary excretion and an estimated 40% by biliary excretion.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Heart failure. Pregnancy, lactation.

Special Warning

Renal Impairment: Based on serum-creatinine concentrations: 105-265 micromoles/l: 75% of the usual dose; >265 micromoles/l: 50% of the usual dose.

Hepatic Impairment: Based on serum bilirubin concentrations of 12-30 mcg/ml: 75% of the usual dose; >30 mcg/ml: 50% of the usual dose.

Acute Overdose

Severe myelosupression, cardiotoxicity with or without transient reversible ECG changes leading to CHF. Treatment is supportive and symptomatic.

Storage Condition

Powder for inj: Store at 15-25° C. Solution for inj & liposomal inj: Refrigerate at 2-8° C. Do not freeze.

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