Daunorubicin

• Class: Anthracycline antibiotic – cytotoxic chemotherapy.
• Type: IV cytotoxic agent.

Mechanism of Action (MOA)

• Intercalates DNA → disrupts DNA and RNA synthesis.
• Inhibits topoisomerase II, preventing DNA relegation → DNA strand breaks.
• Generates free radicals, causing additional DNA and cell membrane damage.
• Cell cycle non-specific, but primarily affects S phase.

Clinical Uses

• Acute myeloid leukemia (AML) – often in combination with cytarabine (e.g., 7+3 regimen).
• Acute lymphoblastic leukemia (ALL) – in some pediatric protocols.
• Part of other combination regimens for hematologic malignancies.

Dosing (Adults)

• AML induction: 60–90 mg/m² IV daily for 3 days (in 7+3 regimen with cytarabine).
• Dose adjustments:
  • Hepatic impairment (bilirubin >3 mg/dL → dose reduction or hold).
  • Renal impairment – usually minor adjustment; mainly hepatically metabolized.

Toxicities

• Cardiotoxicity – cumulative, dose-limiting; risk of heart failure.
• Myelosuppression – neutropenia, thrombocytopenia, anemia.
• Gastrointestinal: nausea, vomiting, mucositis.
• Alopecia.
• Red discoloration of urine (harmless, due to drug).
• Extravasation → severe local tissue necrosis.

Monitoring

• CBC with differential.
• Cardiac function: baseline and periodic echocardiogram or MUGA scan (LVEF).
• Liver function tests.
• Signs of extravasation during IV administration.
• Monitor for infection and bleeding due to myelosuppression.

Summary

Daunorubicin (Cerubidine®) is an anthracycline used primarily in AML induction. Key concerns are cumulative cardiotoxicity, myelosuppression, mucositis, and extravasation, requiring CBC monitoring, cardiac assessment, and careful IV administration.