Daunorubicin

Publication Details

OVERVIEW

Introduction

Daunorubicin is an anthracycline antibiotic that has antineoplastic activity and is used in the therapy of acute leukemia and AIDS related Kaposi sarcoma. Daunorubicin is associated with a low rate of transient serum enzyme and bilirubin elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury with jaundice.

Background

Daunorubicin (daw” noe roo’ bi sin) is a parenterally administered, cytotoxic antibiotic which is believed to act by intercalating between DNA base pairs and uncoiling the DNA helix, which results in inhibition of DNA synthesis and apoptosis of rapidly dividing cells. Daunorubicin has potent activity in acute leukemia and was approved for this indication in the United States in 1979. Current indications include induction of remission in acute lymphocytic and non-lymphocytic (myelogenous) leukemia both in children and adults. Daunorubicin is available as a solution or a powder for injection in 20 and 50 mg vials [5 mg/mL] generically and under the brand name Cerubidine. Daunorubicin is given intravenously, typically in a regimen of once daily for 3 days during induction and for two days of subsequent courses. The dosage varies by indication, body surface area, patient age and renal and hepatic function. A liposomal formulation of daunorubicin is available as a first line therapy for advanced HIV related Kaposi sarcoma. Common side effects of daunorubicin include bone marrow suppression, nausea, vomiting, mucositis, diarrhea, alopecia, skin rash, red urine and fever. High doses or prolonged therapy can cause serious cardiac toxicity which is a major dose limiting side effect. Local extravasation of daunorubicin causes severe local tissue injury.

Hepatotoxicity

Chemotherapy with daunorubicin in combination with other agents is associated with serum enzyme elevations in a proportion of patients depending upon the dose and other agents used. ALT elevations during daunorubicin therapy are usually asymptomatic and transient and may resolve without dose modification. In many instances, it is difficult to attribute the liver test abnormalities to daunorubicin, because of the exposure to other potentially hepatotoxic agents. There have been no convincing instances of acute, clinically apparent idiosyncratic liver injury with jaundice associated with daunorubicin therapy. However, high doses of daunorubicin given in combination with other antineoplastic agents have been linked to cases of sinusoidal obstruction syndrome, typically presenting with right upper quadrant pain 10 to 30 days after the infusion, followed by weight gain, ascites and liver test abnormalities. Fatalities due to hepatic failure have occurred, but most patients recover within 1 to 3 months of onset.

Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).

Mechanism of Injury

While hepatotoxicity from daunorubicin may be rare, it is likely due to direct hepatic toxicity. Daunorubicin is metabolized in the liver via microsomal enzymes and production of a toxic or immunogenic intermediate may trigger liver injury.

Outcome and Management

The hepatic injury due to daunorubicin varies in severity from mild, transient and asymptomatic liver enzyme elevations to acute liver failure due to sinusoidal obstruction syndrome. Therapy for sinusoidal obstruction syndromeshould be based upon careful management of fluid balance and avoidance of further injury. Sinusoidal obstruction syndrome has become rare, largely due to avoidance of high dose chemotherapy with agents that have been linked with it such as busulfan and cyclosphosphamide. Intravenous defibrotide has been approved for used in paitents with severe sinusoidal obstruction syndrome and major organ damage. There is no information on cross sensitivity to hepatic injury between daunorubicin and other antineoplastic agents, including anthracycline antibiotics.

Drug Class: Antineoplastic Agents

Other Drugs in the Subclass, Antibiotics, Cytotoxic: Bleomycin, Dactinomycin, Doxorubicin, Epirubicin, Idarubicin, Mitomycin, Mitoxantrone, Plicamycin

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Daunorubicin – Cerubidine®

DRUG CLASS

Antineoplastic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 27 December 2017

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