Drug Guide
Cytarabine; Daunorubicin (Vyxeos)
Classification
Therapeutic: Antineoplastic agent (Chemotherapy)
Pharmacological: Combination anthracycline and antimetabolite
FDA Approved Indications
- Acute myeloid leukemia (AML), particularly therapy-related or secondary AML and AML with myelodysplasia-related changes
Mechanism of Action
Cytarabine is a nucleoside analog that inhibits DNA synthesis; Daunorubicin intercalates into DNA, inhibiting topoisomerase II and generating free radicals, leading to DNA damage and cell death.
Dosage and Administration
Adult: As per protocol; Vyxeos is administered via IV infusion, typically in cycles every 21-28 days, dosing based on body surface area.
Pediatric: Not commonly used in pediatric patients; consult specific pediatric protocols.
Geriatric: Use with caution; consider comorbidities and overall health status.
Renal Impairment: Dose adjustments may be necessary based on severity of impairment.
Hepatic Impairment: No specific data; use cautiously and monitor liver function.
Pharmacokinetics
Absorption: Administered IV, hence 100% bioavailability.
Distribution: Widely distributed; crosses the blood-brain barrier poorly.
Metabolism: Cytarabine is metabolized in the liver; daunorubicin undergoes hepatic metabolism.
Excretion: Primarily renal; metabolites and unchanged drugs excreted in urine.
Half Life: Cytarabine: approximately 3-10 hours; Daunorubicin: approximately 20-48 hours.
Contraindications
- Hypersensitivity to cytarabine, daunorubicin, or components of the formulation.
- Severe hepatic or renal impairment without dose adjustment.
Precautions
- Myelosuppression, cardiotoxicity, hepatotoxicity, renal toxicity, risk of secondary malignancies. Monitor cardiac function especially with cumulative doses of daunorubicin.
- Pregnancy category D: risk to fetus; use only if benefits outweigh risks.
- Patient should be monitored for signs of infection, bleeding, and organ toxicity.
Adverse Reactions - Common
- Myelosuppression (neutropenia, thrombocytopenia, anemia) (Very common)
- Nausea and vomiting (Common)
- Mucositis (Common)
Adverse Reactions - Serious
- Cardiotoxicity (dilated cardiomyopathy, heart failure) (Uncommon to rare with cumulative dose)
- Hepatotoxicity (Rare)
- Secondary malignancies (e.g., acute leukemia, myelodysplastic syndromes) (Rare)
- Severe infections due to immunosuppression (Common)
Drug-Drug Interactions
- Other myelosuppressive agents, anthracyclines, high-dose cytarabine, hepatotoxic drugs, cardiotoxic agents.
Drug-Food Interactions
- None specifically noted.
Drug-Herb Interactions
- Potential interactions with herbals affecting coagulation or organ function; consult specific sources.
Nursing Implications
Assessment: Monitor complete blood counts, liver and renal function, cardiac status, signs of infection, and infusion site for extravasation.
Diagnoses:
- Risk for infection, risk for bleeding due to thrombocytopenia, impaired tissue integrity.
Implementation: Administer as per protocol, monitor for adverse effects, and provide supportive care, including antiemetics and growth factor support as indicated.
Evaluation: Assess blood counts regularly, monitor organ function, and evaluate patient response and adverse events.
Patient/Family Teaching
- Report signs of infection, bleeding, or unusual symptoms immediately.
- Use effective contraception during and for some time after therapy.
- Maintain hydration to help reduce toxicity.
Special Considerations
Black Box Warnings:
- Extravasation can cause severe tissue necrosis (cytarabine).
- Cardiotoxicity associated with cumulative daunorubicin doses.
Genetic Factors: Genetic variations in enzymes metabolizing cytarabine and daunorubicin may affect toxicity and efficacy.
Lab Test Interference: May cause transient elevations in liver enzymes and serum bilirubin.
Overdose Management
Signs/Symptoms: Severe myelosuppression, mucositis, cardiotoxicity, CNS symptoms (seizures, coma) with high doses.
Treatment: Supportive care, including granulocyte colony-stimulating factor (G-CSF), transfusions, antiemetics, and cardioprotective agents as indicated.
Storage and Handling
Storage: Store at room temperature (15-25°C), protected from light.
Stability: Stable under recommended conditions; use aseptic technique during preparation.