Version July 2025
Daunorubicin and cytarabine (liposomal) has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors.
General dosage considerations:
Safety: Prior to each dose, calculate the cumulative anthracycline exposure (treatment is not recommended in patients whose exposure has reached the maximum cumulative anthracycline threshold). Assess cardiac function (use is not recommended in patients with left ventricular ejection fraction less than normal), liver, and renal function prior to therapy initiation; also evaluate complete blood counts in addition to cardiac function and liver/renal function prior to each consolidation cycle. Do not initiate a new cycle until ANC recovers to >500/mm3 and platelets recover to >50,000/mm3.
Dosing: Calculate dose based on the daunorubicin component. Therapy consists of 1 to 2 induction cycles followed by up to 2 consolidation cycles.
Clinical considerations: Daunorubicin/cytarabine (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Acute myeloid leukemia (newly diagnosed for therapy-related AML [t-AML] or AML with myelodysplasia-related changes [AML-MRC]):
Induction (first cycle): IV: Daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 (liposomal) on days 1, 3, and 5 (Ref).
Induction (second cycle in patients who do not achieve remission with first cycle): IV: Daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 (liposomal) on days 1 and 3 (Ref); the second induction cycle may be administered 2 to 5 weeks after the first induction cycle (if no unacceptable toxicity with previous cycle).
Consolidation: IV: Daunorubicin 29 mg/m2 and cytarabine 65 mg/m2 (liposomal) on days 1 and 3 (Ref); administer the first consolidation cycle 5 to 8 weeks after the start of the last induction; administer the second consolidation cycle 5 to 8 weeks after the start of the first consolidation cycle.
Missed dose: If a planned dose is missed, administer the dose as soon as possible and adjust the schedule accordingly (maintain the treatment interval).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥15 mL/minute: No dosage adjustment necessary.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
ESRD on hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Total bilirubin ≤3 mg/dL: No dosage adjustment necessary.
Total bilirubin >3 mg/dL: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Cardiotoxicity: Discontinue daunorubicin and cytarabine (liposomal) in patients with impaired cardiac function unless the benefits of continued treatment outweigh the toxicity risks. Use is not recommended in patients with left ventricular ejection fraction (LVEF) less than normal.
Copper toxicity: Discontinue daunorubicin and cytarabine (liposomal) if signs/symptoms of acute copper toxicity occur.
Hematologic toxicity: Do not initiate a new cycle until ANC recovers to >500/mm3 and platelets recover to >50,000/mm3. Hematologic toxicity may require platelet transfusion support.
Hypersensitivity reactions:
Mild symptoms: Interrupt infusion immediately and manage symptoms as clinically appropriate. Upon symptom resolution, reinitiate infusion at 50% of the previous infusion rate; consider premedication with antihistamines and/or corticosteroids with subsequent daunorubicin and cytarabine (liposomal) doses.
Moderate symptoms: Interrupt infusion immediately and manage symptoms as clinically appropriate. Do not reinitiate infusion. Premedicate with antihistamines and/or corticosteroids with subsequent daunorubicin and cytarabine (liposomal) doses prior to initiating infusion at the same rate.
Severe or life-threatening symptoms: Interrupt infusion immediately and manage symptoms as clinically appropriate; monitor until symptom resolution. Permanently discontinue daunorubicin and cytarabine (liposomal).
Refer to adult dosing.
(For additional information see "Liposomal daunorubicin and cytarabine: Pediatric drug information")
Note: Daunorubicin/cytarabine (liposomal) is a fixed-dose combination product and is NOT interchangeable with other preparations of daunorubicin or cytarabine (conventional or liposomal). Calculate dose based on the daunorubicin component. Prior to each dose, calculate the cumulative anthracycline exposure; the risk for cardiomyopathy increases as the cumulative dose increases (≥250 mg/m2 of doxorubicin isotoxic equivalent dose in pediatric patients <18 years and 550 mg/m2 of doxorubicin isotoxic equivalent dose in patients >18 years) but is also dependent on other/additional risk factors; interpatient variability exists (eg, some patients may experience left ventricular dysfunction at lower doses). To calculate doxorubicin equivalent dose of nonliposomal daunorubicin, multiply total daunorubicin dose by 0.5 (Ref).
Note: Daunorubicin/cytarabine (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Acute myeloid leukemia (newly diagnosed for therapy-related AML [t-AML] or AML with myelodysplasia-related changes [AML-MRC]):
Children and Adolescents:
Induction (first cycle): IV: Daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 (liposomal) on days 1, 3, and 5.
Induction (second cycle in patients who do not achieve remission with first cycle): IV: Daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 (liposomal) on days 1 and 3; the second induction cycle may be administered 2 to 5 weeks after the first induction cycle (if no unacceptable toxicity with previous cycle).
Consolidation: IV: Daunorubicin 29 mg/m2 and cytarabine 65 mg/m2 (liposomal) on days 1 and 3; administer the first consolidation cycle 5 to 8 weeks after the start of the last induction; administer the second consolidation cycle 5 to 8 weeks after the start of the first consolidation cycle.
Acute myeloid leukemia, relapsed: Limited data available: Children and Adolescents: IV: Daunorubicin 60 mg/m2 and cytarabine 135 mg/m2 (liposomal) on days 1, 3, and 5 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity: Children and Adolescents:
Cardiotoxicity: Discontinue daunorubicin and cytarabine (liposomal) in patients with impaired cardiac function unless the benefits of continued treatment outweigh the toxicity risks.
Hematologic toxicity: Do not initiate a new cycle until ANC recovers to >500/mm3 and platelets recover to >50,000/mm3. Hematologic toxicity may require platelet transfusion support.
Hypersensitivity reactions:
Mild symptoms: Interrupt infusion immediately and manage symptoms as clinically appropriate. Upon symptom resolution, reinitiate infusion at 50% of the previous infusion rate; consider premedication with antihistamines and/or corticosteroids with subsequent daunorubicin and cytarabine (liposomal) doses.
Moderate symptoms: Interrupt infusion immediately and manage symptoms as clinically appropriate. Do not reinitiate infusion. Premedicate with antihistamines and/or corticosteroids with subsequent daunorubicin and cytarabine (liposomal) doses prior to initiating infusion at the same rate.
Severe or life-threatening symptoms: Interrupt infusion immediately and manage symptoms as clinically appropriate; monitor until symptom resolution. Permanently discontinue daunorubicin and cytarabine (liposomal).
Children and Adolescents:
CrCl 30 to 89 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage renal disease: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Children and Adolescents:
Total bilirubin ≤3 mg/dL: No dosage adjustment necessary.
Total bilirubin >3 mg/dL: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Cardiac arrhythmia (30%), cardiotoxicity (20%), chest pain (17%), edema (51%), hypertension (18%), hypotension (20%)
Dermatologic: Pruritus (15%), skin rash (54%)
Endocrine & metabolic: Hyponatremia (grades 3/4: 6% to 14%)
Gastrointestinal: Abdominal pain (33%), colitis (≤45%), constipation (40%), decreased appetite (29%), diarrhea (≤45%; grades 3/4: ≤3%), hemorrhoids (11%), nausea (47%; grades 3/4: 1%), stomatitis (44%; grades 3/4: 1%), vomiting (24%)
Hematologic & oncologic: Anemia (100%), febrile neutropenia (68%; grades 3/4: 66%), hemorrhage (70%; grades 3/4: 10%), neutropenia (100%; grade 4 [prolonged]: 10% to 17%), petechia (11%), thrombocytopenia (100%; grade 3 [prolonged]: 25% to 28%),
Hypersensitivity: Transfusion reaction (11%)
Infection: Bacteremia (24%), fungal infection (18%), sepsis (11%)
Local: Injection-site reaction (16%; includes catheter and device site)
Nervous system: Anxiety (14%), chills (23%), delirium (16%), dizziness (18%), fatigue (32%), headache (33%), sleep disorder (25%)
Neuromuscular & skeletal: Musculoskeletal pain (38%)
Ophthalmic: Visual impairment (11%)
Renal: Renal insufficiency (11%)
Respiratory: Cough (33%), dyspnea (32%), hypoxia (18%), pleural effusion (16%), pneumonia (26%), upper respiratory tract infection (18%)
Miscellaneous: Fever (17%)
1% to 10%:
Endocrine & metabolic: Hypoalbuminemia (grades 3/4: 2% to 7%), hypokalemia (grades 3/4: 6% to 9%)
Gastrointestinal: Dyspepsia (<10%)
Hepatic: Abnormal alanine aminotransferase (grades 3/4: ≤5%), hyperbilirubinemia (grades 3/4: 2% to 6%)
Nervous system: Hallucination (<10%)
Ophthalmic: Conjunctivitis (<10%), dry eye syndrome (<10%), eye irritation (<10%), eye pain (<10%), injected sclera (<10%), ocular hyperemia (<10%), periorbital edema (<10%), swelling of eye (<10%)
Otic: Deafness (<10%)
Respiratory: Pneumonitis (<10%)
Postmarketing: Hypersensitivity: Infusion-related reaction
Serious hypersensitivity to daunorubicin, cytarabine, or any component of the formulation
Concerns related to adverse effects:
• Bone marrow suppression: Neutropenia, thrombocytopenia, and anemia occurred in all patients in a clinical study comparing daunorubicin and cytarabine (liposomal) to conventional 7 + 3 therapy; prolonged thrombocytopenia and neutropenia were also observed more frequently with the daunorubicin and cytarabine (liposomal) arm.
• Cardiotoxicity: Cardiotoxicity may occur due to the anthracycline component (daunorubicin) of the formulation. Risk factors for cardiotoxicity include prior exposure to anthracyclines, preexisting cardiac disease, previous mediastinal radiotherapy, or concomitant use of cardiotoxic medications. Other risk factors for anthracycline-induced cardiotoxicity include age 60 and older at time of treatment and 2 or more cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, or obesity) during or after treatment (ASCO [Armenian 2017]). A total cumulative dose of daunorubicin (conventional) 550 mg/m2 (400 mg/m2 in patients with prior mediastinal radiation) has been associated with an increased incidence of heart failure; calculate the total lifetime cumulative anthracycline dose prior to each cycle of daunorubicin and cytarabine (liposomal).
• Copper exposure: Reconstituted daunorubicin/cytarabine (liposomal) contains 5 mg/mL copper gluconate (of which 14% is elemental copper). Assess copper content in patients with disorders of copper metabolism. There is no clinical experience with use of this medication in patients with Wilson disease or other copper-related metabolic disorders. Consult with a hepatologist and nephrologist for management of acute copper toxicity.
• Extravasation: Daunorubicin (conventional) is a potent vesicant; extravasation of conventional daunorubicin has been associated with severe local tissue necrosis. The daunorubicin (liposomal) component of the formulation may be an irritant (injection site reactions have been reported). Daunorubicin/cytarabine (liposomal) is for IV administration only; do not administer IM or SUBQ. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
• Hemorrhage: Serious hemorrhage events (associated with prolonged severe thrombocytopenia), including grade 3 and higher events, have occurred; fatal CNS hemorrhages have also been reported. In a clinical study, epistaxis was the most frequently reported hemorrhagic event.
• Hypersensitivity reactions: Serious or fatal hypersensitivity reactions (including anaphylactic reactions) have been reported with daunorubicin and cytarabine.
Special populations:
• Older adult: Bleeding events occurred more frequently in patients 65 years and older compared to younger patients.
Dosage form specific issues:
• Formulations: Daunorubicin/cytarabine (liposomal) has different dosage recommendations than daunorubicin (conventional), cytarabine (conventional), daunorubicin (liposomal), and cytarabine (liposomal). Verify drug name and dose prior to preparation and administration to avoid dosing errors. The schedule and pharmacokinetics also vary among the formulations. Do not substitute other daunorubicin- or cytarabine-containing products for daunorubicin and cytarabine (liposomal).
Incidence of delayed cardiac toxicity and congestive heart failure during early adulthood has increased in pediatric patients due to increasing long-term survival; risk factors include: Young treatment age (<5 years), cumulative anthracycline exposure (if <18 years at time of treatment: ≥250 mg/m2 doxorubicin; if ≥18 years at time of treatment: ≥550 mg/m2 doxorubicin), chest radiation ≥15 Gy combined with ≥100 mg/m2 doxorubicin, and concomitant cardiotoxic therapy. Long-term monitoring is recommended for all pediatric patients (Long-Term Follow-Up Guidelines [COG 2018]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension Reconstituted, Intravenous [preservative free]:
Vyxeos: Daunorubicin 44 mg and cytarabine 100 mg (1 ea) [contains trolamine (triethanolamine)]
No
Suspension (reconstituted) (Vyxeos Intravenous)
44-100 mg (per each): $12,921.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension Reconstituted, Intravenous:
Vyxeos: Daunorubicin 44 mg and cytarabine 100 mg (1 ea) [contains trolamine (triethanolamine)]
Daunorubicin/cytarabine (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
IV: For IV administration only; do not administer IM or SUBQ. Administer over 90 minutes (for induction and consolidation cycles) via an infusion pump through a central venous or peripherally inserted central catheter. May use an in-line membrane filter with a pore diameter ≥15 micron. Flush the line with NS or D5W after infusion. Do not mix with or administer with any other medications. If infusion-related reactions occur, premedication with antihistamines and/or corticosteroids may be necessary.
The daunorubicin (liposomal) component may be an irritant; avoid extravasation.
Note: Daunorubicin/cytarabine (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Parenteral: IV: For IV administration only; do not administer IM or SUBQ. If dose is diluted in <500 mL, use non-DEHP infusion bags and lines. Administer over 90 minutes via an infusion pump through a central venous or peripherally inserted central catheter. May use an in-line membrane filter with a pore diameter ≥15 micron. Flush the line with NS or D5W after infusion. Do not mix with or administer with any other medications. If infusion-related reactions occur, premedication with antihistamines and/or corticosteroids may be necessary.
The daunorubicin (liposomal) component may be an irritant; avoid extravasation.
Missed dose: If a planned dose is missed, administer the dose as soon as possible and adjust the schedule accordingly to maintain the treatment interval.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Acute myeloid leukemia: Treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients ≥1 year of age.
Daunorubicin and cytarabine (liposomal) may be confused with cytarabine (conventional), cytarabine (liposomal), dactinomycin, daunorubicin (conventional), daunorubicin (liposomal), doxorubicin, doxorubicin liposomal, epirubicin, idarubicin, valrubicin
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Daunorubicin and cytarabine (liposomal) is a fixed formulation and has different dosing recommendations than daunorubicin (conventional), daunorubicin (liposomal), cytarabine (conventional), and cytarabine (liposomal). Do not substitute with other daunorubicin- or cytarabine-containing formulations. Use caution during product selection, preparation, and administration.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Ado-Trastuzumab Emtansine: May increase cardiotoxic effects of Anthracyclines. Management: When possible, patients treated with ado-trastuzumab emtansine should avoid anthracycline-based therapy for up to 7 months after stopping ado-trastuzumab emtansine. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider Therapy Modification
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG (Intravesical): Myelosuppressive Agents may decrease therapeutic effects of BCG (Intravesical). Myelosuppressive Agents may increase adverse/toxic effects of BCG (Intravesical). Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Bevacizumab: May increase cardiotoxic effects of Anthracyclines. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Cedazuridine: May increase serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Cladribine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CycloPHOSphamide: May increase cardiotoxic effects of Anthracyclines. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fam-Trastuzumab Deruxtecan: May increase cardiotoxic effects of Anthracyclines. Management: When possible, patients treated with fam-trastuzumab deruxtecan should avoid anthracycline-based therapy for up to 7 months after stopping fam-trastuzumab deruxtecan. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider Therapy Modification
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Margetuximab: Anthracyclines may increase adverse/toxic effects of Margetuximab. Specifically, the risk of cardiac dysfunction may be increased. Management: Avoid anthracycline-based therapy for up to 4 months after discontinuing margetuximab due to an increased risk of cardiac dysfunction. If anthracyclines must be used with margetuximab monitor cardiac function closely. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Taxane Derivatives: May increase adverse/toxic effects of Anthracyclines. Specifically, the risk of cardiotoxicity may be increased with this combination. Taxane Derivatives may increase serum concentration of Anthracyclines. Management: Administer doxorubicin before paclitaxel, administer idarubicin after paclitaxel has been stopped for 5 half lives, consider use of liposomal doxorubicin, epirubicin, or docetaxel instead of doxorubicin/paclitaxel. Monitor for cardiovascular toxicities. Risk D: Consider Therapy Modification
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Trastuzumab: May increase cardiotoxic effects of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab. Risk D: Consider Therapy Modification
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Evaluate pregnancy status prior to use in women of reproductive potential; effective contraception should be used during therapy and for at least 6 months after the last dose. Male patients with female partners of reproductive potential should also use effective contraception during therapy and for at least 6 months after the last dose.
Based on the mechanism of action, anecdotal data of cytarabine use in pregnant women, and data from animal reproduction studies, use of daunorubicin and cytarabine (liposomal) in pregnancy may cause fetal harm.
Also refer to individual monographs for additional information.
It is not known if daunorubicin, cytarabine, or their metabolites are present in breast milk. According to the manufacturer, breastfeeding is not recommended during therapy or for at least 2 weeks after the last dose.
Also refer to individual monographs.
Complete blood counts (prior to treatment and each consolidation cycle), liver and renal function tests (prior to treatment and each consolidation cycle). Evaluate pregnancy status prior to treatment initiation (in women of reproductive potential). Monitor total serum copper, serum non-ceruloplasmin bound copper, 24-hour urine copper levels (in patients with Wilson disease or other copper-related metabolic disorders). Assess cardiac function via ECG, multigated acquisition (MUGA), or echocardiogram (ECHO) prior to treatment initiation, consolidation therapy; repeat cardiac assessment via MUGA or ECHO prior to consolidation therapy with daunorubicin and cytarabine (liposomal) and as clinically necessary. Perform serial neuropsychological exams in patients with Wilson disease or other copper-related metabolic disorders. Monitor infusion site (for extravasation) and for nausea/vomiting. Monitor for signs/symptoms of hemorrhage and hypersensitivity reactions.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Daunorubicin and cytarabine (liposomal) is a combination product with a fixed 1:5 (daunorubicin:cytarabine) molar ratio; this ratio has been shown to have synergistic effects in killing leukemia cells in vitro and in animal models.
Daunorubicin (conventional) inhibits DNA and RNA synthesis by intercalation between DNA base pairs and by steric obstruction. Daunomycin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA. Cytarabine (conventional) is a pyrimidine analog and is incorporated into DNA; however, the primary action is inhibition of DNA polymerase resulting in decreased DNA synthesis and repair. The degree of cytotoxicity correlates linearly with incorporation into DNA; therefore, incorporation into the DNA is responsible for drug activity and toxicity. Cytarabine is specific for the S phase of the cell cycle (blocks progression from the G1 to the S phase).
Per animal data, liposomes are taken up intact by bone marrow cells (to a greater degree in leukemia cells versus normal bone marrow cells) and are degraded following cellular internalization, thus releasing cytarabine and daunorubicin within the cells.
Note: Exposures in pediatric patients (1 to <17 years) were similar to adults.
Distribution: Daunorubicin 6.6 L; Cytarabine 7.1 L.
Metabolism: Upon release from the liposomes, daunorubicin is catalyzed by aldoketo reductase and carbonyl reductase to daunorubicinol (active metabolite); cytarabine is metabolized by cytidine deaminase to Ara-U (inactive metabolite).
Half-life elimination: 31.5 hours (daunorubicin); 40.4 hours (cytarabine) with >99% of drug(s) remaining encapsulated in the liposomes.
Excretion: Urine (9% daunorubicin; 71% cytarabine and Ara-U).
Clearance: 0.16 L/hour (daunorubicin); 0.13 L/hour (cytarabine).
Altered kidney function: In patients with moderate impairment (CrCl 30 to 59 mL/minute), the mean AUCtau of total cytarabine and daunorubicin was decreased 8% and 6%, respectively, compared to patients with normal renal function. In patients with severe impairment (CrCl 15 to 29 mL/minute), the mean AUCtau of total cytarabine and daunorubicin was increased 0.4% and decreased 3%, respectively, compared to patients with normal renal function.
