DAUNOXOME
Clinical safety rating
cautionComprehensive clinical and safety monograph for DAUNOXOME (DAUNOXOME).
Comprehensive clinical and safety monograph for DAUNOXOME (DAUNOXOME).
Treatment of advanced HIV-associated Kaposi sarcoma as first-line therapyAcute myeloid leukemia (off-label)Acute lymphoblastic leukemia (off-label)
Daunorubicin intercalates between DNA base pairs, inhibiting topoisomerase II activity and preventing DNA replication and transcription. Liposomal encapsulation (DaunoXome) alters distribution, reducing cardiotoxicity and enhancing tumor delivery.
| Metabolism | Primarily hepatically metabolized via reduction to daunorubicinol by cytoplasmic reductases, and additionally by aldo-keto reductases and NADPH-dependent enzymes. Excretion: biliary and renal. |
| Excretion | Primarily biliary/fecal (40-50% as unchanged drug and metabolites); renal excretion accounts for approximately 5-15% as unchanged drug and metabolites over 5 days. |
| Half-life | Terminal elimination half-life is approximately 30-40 hours (range 20-48 h); prolonged compared to conventional doxorubicin due to liposomal encapsulation, allowing extended drug exposure. |
| Protein binding | Approximately 90-95% bound, primarily to plasma proteins (albumin); minimal displacement interactions reported. |
| Volume of Distribution | Vd is approximately 2-3 L/kg, indicating extensive tissue distribution; liposomal formulation concentrates in RES organs (liver, spleen) and tumors with leaky vasculature. |
| Bioavailability | Only administered intravenously; oral bioavailability is negligible (<5%) due to extensive first-pass metabolism and instability in GI tract. |
| Onset of Action | Intravenous: clinical effects (e.g., myelosuppression, antitumor activity) typically observed within 1-3 weeks after administration. |
| Duration of Action | Duration of action is prolonged; myelosuppression may persist for 2-3 weeks, with nadir counts occurring around day 10-14. Cumulative dose-limiting cardiotoxicity risk increases with total exposure. |
| Molecular Weight | 563.97 |
60-80 mg/m² intravenously over 1 hour every 2-4 weeks.
| Dosage form | INJECTABLE, LIPOSOMAL |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) and consider dose reduction. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: reduce dose by 50% or avoid use. |
| Pediatric use | 60-80 mg/m² intravenously over 1 hour every 2-4 weeks; safety and efficacy not established in children under 2 years. |
| Geriatric use | No specific dose adjustment; monitor for increased toxicity due to age-related organ dysfunction. |
| 1st trimester | Contraindicated: major teratogen; risk of fetal malformations including cardiac and neural tube defects. |
| 2nd trimester | Contraindicated: risk of fetal toxicity and pregnancy loss. |
| 3rd trimester | Contraindicated: risk of neonatal myelosuppression and cardiotoxicity. |
Clinical note
Comprehensive clinical and safety monograph for DAUNOXOME (DAUNOXOME).
| Placental transfer | Daunorubicin crosses the placenta; fetal plasma levels reach approximately 75% of maternal levels. |
| Breastfeeding | Daunorubicin is excreted into breast milk; potential for serious adverse reactions in nursing infants (e.g., immunosuppression, carcinogenesis). Advise to discontinue breastfeeding during treatment and for at least 10 days after last dose. |
| Lactation Rating | L5 (Avoid) |
| Teratogenic Risk | Daunorubicin (DaunoXome) is teratogenic in animal studies. First trimester: Avoid; major congenital malformations (cardiac, skeletal) reported. Second/third trimester: Use only if benefit outweighs risk; risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Fetal toxicity is dose-dependent. |
| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver and renal function, cardiac function (echocardiogram or MUGA scan) before and during therapy. Assess fetal growth and amniotic fluid volume via ultrasound monthly during second and third trimesters. Monitor for preterm labor and signs of fetal distress. |
| Fertility Effects | Daunorubicin is gonadotoxic. In males: may cause oligospermia or azoospermia, potentially permanent. In females: may cause premature ovarian failure, amenorrhea, and reduced fertility. Risk is dose- and age-dependent. Consider fertility preservation prior to treatment. |
■ FDA Black Box Warning
DaunoXome should be administered under the supervision of a physician experienced in cancer chemotherapy. Severe myelosuppression occurs. Cardiac toxicity, including potentially irreversible cardiomyopathy, may occur, especially with cumulative doses >600 mg/m². Extravasation can cause severe tissue necrosis.
| Serious Effects |
Hypersensitivity to daunorubicinSevere hepatic impairment (Child-Pugh Class C)Severe cardiac dysfunctionPersistent severe myelosuppressionPregnancy (teratogenic)
| Precautions | Monitor cardiac function (LVEF) regularly; cumulative dose limit 600 mg/m². Monitor blood counts for myelosuppression. Infusion reactions (hypotension, dyspnea) may occur. Not interchangeable with conventional daunorubicin. |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition altering drug metabolism. No other significant food interactions. Maintain adequate hydration to prevent tumor lysis syndrome. |
| Clinical Pearls | DaunoXome (liposomal daunorubicin) has reduced cardiotoxicity compared to conventional daunorubicin due to preferential uptake by reticuloendothelial system. Cumulative lifetime dose limit is 600-800 mg/m² in adults (higher than conventional daunorubicin). Monitor for infusion reactions (flushing, dyspnea) especially during first dose. Myelosuppression is dose-limiting. Premedicate with antiemetics. Not interchangeable with conventional daunorubicin on mg/m² basis. |
| Patient Advice | This medication may cause temporary hair loss, nausea, vomiting, and mouth sores. · Report any signs of infection (fever, chills) or unusual bleeding/bruising immediately. · Avoid grapefruit and grapefruit juice during treatment. · Use effective contraception during therapy and for 6 months after last dose. · Do not receive live vaccines during treatment. |
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