Usage
Daunorubicin is primarily prescribed for the treatment of acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). It is also used in some treatment regimens for other cancers like Ewing’s sarcoma, Kaposi’s sarcoma, Hodgkin’s disease, non-Hodgkin’s lymphoma, lymphosarcoma, chronic myelogenous leukemia, rhabdomyosarcoma, and Wilm’s tumor. It is classified as an antineoplastic agent, specifically an anthracycline topoisomerase II inhibitor. Daunorubicin works by intercalating into DNA, inhibiting topoisomerase II, and disrupting DNA and RNA synthesis, ultimately leading to cell death.
Alternate Names
Daunorubicin hydrochloride is also known as Daunomycin. Brand names include Cerubidine and Daunoblastina.
How It Works
Pharmacodynamics: Daunorubicin exerts its cytotoxic effect by multiple mechanisms. Primarily, it intercalates between DNA base pairs, disrupting DNA and RNA synthesis. It also inhibits topoisomerase II, an enzyme crucial for DNA replication and repair. These actions prevent cell division and lead to apoptosis (programmed cell death) of cancerous cells.
Pharmacokinetics: Daunorubicin is administered intravenously. It is rapidly distributed throughout the body, with highest concentrations found in the liver, spleen, kidney, lung, and heart. It is metabolized in the liver to daunorubicinol, an active metabolite. Elimination is primarily through biliary excretion into feces, with a smaller portion excreted in urine. The terminal half-life is approximately 18.5 hours, but it can vary depending on factors such as hepatic and renal function. Daunorubicin is a substrate of P-glycoprotein (P-gp) efflux transporter.
Dosage
Standard Dosage
Adults:
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AML: 45 mg/m² IV on days 1, 2, and 3 for the first course, and days 1 and 2 for subsequent courses, in combination with cytarabine. Patients over 60 years may receive a reduced dose of 30 mg/m². Higher doses (up to 90 mg/m² for 3 days) have been studied but may increase cardiotoxicity risk.
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ALL: 45 mg/m² IV on days 1, 2, and 3 in combination with other chemotherapeutic agents like vincristine, prednisone, and L-asparaginase.
Children:
- Over 2 years: 25 mg/m² IV weekly. The maximum cumulative dose is 300 mg/m².
- Under 2 years (or <0.5 m² BSA): 1 mg/kg IV weekly. The maximum cumulative dose is 10 mg/kg.
Special Cases:
- Elderly Patients: Dose reduction is often necessary.
- Patients with Renal Impairment: Dosage adjustment is required depending on creatinine clearance. For example, a 50% dose reduction is recommended for creatinine clearance less than 30 mL/min.
- Patients with Hepatic Dysfunction: Dose reductions are based on serum bilirubin levels.
- Patients with Comorbid Conditions: Careful consideration is needed in patients with pre-existing heart disease, as Daunorubicin can worsen cardiac function.
Clinical Use Cases
Daunorubicin is not typically used in the context of intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations. Its primary role is in cancer treatment, specifically leukemias.
Dosage Adjustments
Dose modifications are essential in patients with renal or hepatic impairment and those with pre-existing bone marrow suppression.
Side Effects
Common Side Effects
Nausea, vomiting, mucositis (sores in the mouth and throat), alopecia (hair loss), myelosuppression (decreased blood cell counts), and red discoloration of urine.
Rare but Serious Side Effects
Cardiotoxicity (damage to the heart muscle), secondary leukemias, hypersensitivity reactions, extravasation injury (tissue damage if the drug leaks out of the vein), and tumor lysis syndrome.
Long-Term Effects
Chronic heart failure can occur months or even years after Daunorubicin treatment, especially at higher cumulative doses.
Adverse Drug Reactions (ADR)
Severe myelosuppression, cardiotoxicity, and hypersensitivity reactions require immediate medical intervention.
Contraindications
Hypersensitivity to Daunorubicin, severe pre-existing myelosuppression, significant heart disease (including heart failure, recent myocardial infarction, and severe arrhythmias), severe hepatic impairment, and severe renal impairment.
Drug Interactions
Daunorubicin interacts with numerous medications, including other chemotherapy agents, CYP450 enzyme inducers and inhibitors, and certain antibiotics and antifungals. It can interact with other cardiotoxic agents (e.g. trastuzumab). Alcohol and some medications may increase cardiotoxic potential. Consult a comprehensive drug interaction resource for a full list before co-prescribing.
Pregnancy and Breastfeeding
Daunorubicin is contraindicated in pregnancy (FDA Pregnancy Category D) due to its potential to cause fetal harm. It is also not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Anthracycline; intercalates DNA, inhibits topoisomerase II, and disrupts DNA/RNA synthesis.
- Side Effects: Myelosuppression, cardiotoxicity, mucositis, alopecia, nausea/vomiting, red urine.
- Contraindications: Hypersensitivity, severe myelosuppression, severe heart disease, severe hepatic/renal impairment.
- Drug Interactions: Numerous drug interactions; consult a comprehensive resource.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: CBC, liver function tests, renal function tests, cardiac function (ECG, echocardiogram), serum uric acid levels.
Popular Combinations
Daunorubicin is commonly combined with cytarabine for AML and with vincristine, prednisone, and L-asparaginase for ALL.
Precautions
Closely monitor patients for myelosuppression, cardiotoxicity, infections, and other adverse effects. Pre-screening for underlying heart, liver, and kidney conditions is crucial. Patients should be counseled about the risk of infertility and secondary malignancies. Effective contraception is essential during and after treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Daunorubicin?
A: Dosage depends on several factors including the patient’s age, body surface area, type of cancer, and other health conditions. Refer to the detailed Dosage section above.
Q2: What are the most common side effects?
A: Myelosuppression, nausea/vomiting, mucositis, alopecia, and red-colored urine.
Q3: How is Daunorubicin administered?
A: Intravenously, usually through a rapidly flowing IV infusion.
Q4: What is the maximum cumulative lifetime dose?
A: For adults, the maximum cumulative lifetime dose is typically 550 mg/m² (400 mg/m² in patients with cardiac risk factors). For children over 2 years, it’s 300 mg/m², and for children under 2 years, it’s 10 mg/kg.
Q5: What monitoring parameters are essential during Daunorubicin treatment?
A: Complete blood count (CBC), liver and kidney function tests, cardiac function assessment (ECG, echocardiogram), and monitoring for signs of infection are crucial.
Q6: What are the key contraindications?
A: Hypersensitivity, pre-existing severe myelosuppression, severe heart disease, severe hepatic impairment, and severe renal impairment.
Q7: Can Daunorubicin be given during pregnancy or breastfeeding?
A: No, Daunorubicin is contraindicated in both pregnancy and breastfeeding due to the risk of fetal harm and potential for secretion in breast milk.
Q8: What is the mechanism of Daunorubicin-induced cardiotoxicity?
A: The exact mechanism is not fully understood, but it involves the generation of free radicals, leading to oxidative stress and damage to cardiac myocytes.
Q9. Does Daunorubicin interact with other drugs?
A: Yes. It can interact with other chemotherapy agents, as well as medications metabolized by the liver. Always check for potential drug interactions before prescribing Daunorubicin.
A: Stop the infusion immediately and consult resources for appropriate management, which often involves local injection of an antidote like dexrazoxane.
