CERUBIDINE
Clinical safety rating
cautionComprehensive clinical and safety monograph for CERUBIDINE (CERUBIDINE).
Comprehensive clinical and safety monograph for CERUBIDINE (CERUBIDINE).
Acute myeloid leukemiaAcute lymphoblastic leukemiaChronic myeloid leukemia in blast crisisKaposi's sarcoma (off-label)
Daunorubicin intercalates between DNA base pairs, inhibiting topoisomerase II and preventing DNA replication and transcription, leading to cell death.
| Metabolism | Primarily hepatic metabolism via aldo-keto reductases to daunorubicinol (active metabolite), and further via CYP2D6 and carbonyl reductases. |
| Excretion | Primarily hepatic metabolism with biliary excretion (about 40% as unchanged drug and metabolites in bile). Renal excretion accounts for approximately 8-15% of the dose as unchanged drug and metabolites. Fecal elimination is less than 20%. |
| Half-life | Triphasic elimination: initial half-life 30 min (distribution), intermediate 3-5 hours (metabolism), terminal half-life 20-30 hours (slow elimination from tissues). Clinically relevant for scheduling and myelosuppression monitoring. |
| Protein binding | Approximately 50-70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is high, ranging from 15-30 L/kg, indicating extensive tissue binding and distribution, particularly into erythrocytes and tissues. |
| Bioavailability | Oral bioavailability is less than 5% due to extensive first-pass metabolism; therefore, not administered orally. IV administration results in 100% bioavailability. |
| Onset of Action | IV: Onset within minutes to hours, with peak plasma concentration immediately after infusion. Clinical effect (antileukemic) observed within days. |
| Duration of Action | Duration of cytotoxic effect persists for several days; myelosuppression nadir occurs at 10-14 days, lasting 2-3 weeks. Cardiac toxicity may be delayed and cumulative. |
| Molecular Weight | 563.99 |
45–60 mg/m² IV on days 1–3 every 21–28 days, or 30–60 mg/m² IV daily for 3 days every 3 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10–50 mL/min: reduce dose by 25%; CrCl <10 mL/min: reduce dose by 50%. Hemodialysis: administer after dialysis; dose reduction by 50%. |
| Liver impairment | Child-Pugh A: reduce dose by 25%; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | 25–45 mg/m² IV on days 1–3 every 21 days; neonates: <10 kg: 1 mg/kg IV daily for 3–5 days. |
| Geriatric use | Initiate at lower end of dose range (30 mg/m²/day for 3 days) due to increased myelotoxicity; monitor renal function. |
| 1st trimester | Contraindicated due to teratogenicity; embryo-fetal toxicity and malformations observed in animal studies; avoid pregnancy. |
| 2nd trimester | Contraindicated; risk of fetal harm outweighs potential benefit; consider alternative therapy. |
| 3rd trimester | Contraindicated; may cause fetal toxicity and complications; use only if benefit justifies risk. |
Clinical note
Comprehensive clinical and safety monograph for CERUBIDINE (CERUBIDINE).
| Placental transfer | Active placental transfer occurs; drug is mutagenic and teratogenic in animal models; avoid during pregnancy. |
| Breastfeeding | Not recommended. May be excreted in milk; potential for serious adverse reactions in nursing infants; advise discontinuing breastfeeding during treatment. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Pregnancy Category D. First trimester: High risk of congenital malformations including craniofacial, skeletal, CNS, and cardiac defects. Second and third trimesters: Risk of fetal growth restriction, prematurity, and neonatal myelosuppression. |
| Fetal Monitoring | Complete blood count with differential, liver function tests, renal function tests, cardiac function (echocardiogram or MUGA scan), and bilirubin. Fetal monitoring via ultrasound for growth and anatomy, and non-stress test. |
| Fertility Effects | Causes gonadal suppression and potentially irreversible infertility in both sexes: oligospermia, azoospermia, amenorrhea, and premature ovarian failure, especially with cumulative doses >400 mg/m². |
■ FDA Black Box Warning
Severe myelosuppression; cumulative dose-related cardiotoxicity; extravasation with tissue necrosis; secondary leukemias.
| Serious Effects |
PregnancyHypersensitivity to daunorubicin or other anthracyclinesSevere myelosuppressionPre-existing cardiac diseaseHepatic impairmentConcurrent use with yellow fever vaccine
| Precautions | Bone marrow suppression; cardiac toxicity (cumulative doses >550 mg/m²); hepatic and renal impairment; tumor lysis syndrome; immunosuppression. |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition increasing toxicity. No other specific food restrictions reported. |
| Clinical Pearls | Cerubidine (daunorubicin) is an anthracycline antineoplastic antibiotic; premedicate with antiemetics; monitor for cardiotoxicity (cumulative dose limit 550 mg/m², or 450 mg/m² with prior chest radiation); administer via IV over 15-30 minutes to avoid extravasation (vesicant); observe for rapid lysis syndrome in high-tumor-burden patients; adjust dose for hepatic impairment (bilirubin >1.2 mg/dL). |
| Patient Advice | This drug may cause irreversible heart damage at high cumulative doses; report chest pain, shortness of breath, or swelling of ankles/feet. · You will need regular blood tests to monitor blood cell counts and heart function. · Notify your healthcare provider immediately if you experience pain, redness, or swelling at the injection site. · This medication can cause severe nausea and vomiting; antiemetic therapy will be given. · Avoid grapefruit and grapefruit juice during treatment. · Use effective contraception; do not breastfeed while on this medication. · Your urine may appear reddish-orange for 1-2 days after treatment; this is harmless. |
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