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Liposomal daunorubicin and cytarabine: Drug information

Liposomal daunorubicin and cytarabine: Drug information
(For additional information see "Liposomal daunorubicin and cytarabine: Patient drug information" and see "Liposomal daunorubicin and cytarabine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Do not interchange with other daunorubicin­ and/or cytarabine-containing products:

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.

Brand Names: US
  • Vyxeos
Brand Names: Canada
  • Vyxeos
Pharmacologic Category
  • Antineoplastic Agent, Anthracycline;
  • Antineoplastic Agent, Antimetabolite;
  • Antineoplastic Agent, Antimetabolite (Pyrimidine Analog);
  • Antineoplastic Agent, Topoisomerase II Inhibitor
Dosing: Adult

Note: Calculate dose based on the daunorubicin component. 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 [LVEF] 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. Therapy consists of 1 to 2 induction cycles followed by up to 2 consolidation cycles. Daunorubicin/cytarabine (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]).

Acute myeloid leukemia

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 (Lancet 2018).

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 (Lancet 2018); 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 (Lancet 2018); 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.

Dosing: Kidney Impairment: Adult

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).

Dosing: Hepatic Impairment: Adult

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).

Dosing: Obesity: Adult

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 (ASCO [Griggs 2021]).

Dosing: Adjustment for Toxicity: Adult

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).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(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 (ESC [Zamorano 2016]; Long-Term Follow-Up Guidelines [COG 2018]).

Note: Daunorubicin/cytarabine (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Paw Cho Sing 2019]; ASCO [Hesketh 2020]).

Acute myeloid leukemia

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

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 (Cooper 2020).

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).

Dosing: Kidney Impairment: Pediatric

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).

Dosing: Hepatic Impairment: Pediatric

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).

Adverse Reactions

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

Contraindications

Serious hypersensitivity to daunorubicin, cytarabine, or any component of the formulation

Warnings/Precautions

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).

Warnings: Additional Pediatric Considerations

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]).

Dosage Forms: US

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)]

Generic Equivalent Available: US

No

Pricing: US

Suspension (reconstituted) (Vyxeos Intravenous)

44-100 mg (per each): $12,240.00

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.

Dosage Forms: Canada

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)]

Administration: Adult

Daunorubicin/cytarabine (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]).

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.

Administration: Pediatric

Note: Daunorubicin/cytarabine (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Paw Cho Sing 2019]; ASCO [Hesketh 2020]).

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 Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 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 2016; USP-NF 2020).

Use: Labeled Indications

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.

Medication Safety Issues
Sound-alike/look-alike issues:

Daunorubicin and cytarabine (liposomal) may be confused with cytarabine (conventional), cytarabine (liposomal), dactinomycin, daunorubicin (conventional), daunorubicin (liposomal), doxorubicin, doxorubicin liposomal, epirubicin, idarubicin, valrubicin

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Dosage forms specific issues:

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.

Metabolism/Transport Effects

None known.

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Cedazuridine: May increase the serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Flucytosine: Cytarabine (Conventional) may diminish the therapeutic effect of Flucytosine. Risk C: Monitor therapy

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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 diminish the therapeutic effect 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

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect 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

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Palifermin: May enhance the adverse/toxic effect 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 diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to 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 enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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 enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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 enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect 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 combination

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

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.

Pregnancy Considerations

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.

Breastfeeding Considerations

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.

Monitoring Parameters

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.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

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.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Vyxeos;
  • (AU) Australia: Vyxeos;
  • (BE) Belgium: Vyxeos;
  • (CZ) Czech Republic: Vyxeos liposomal;
  • (DE) Germany: Vyxeos;
  • (ES) Spain: Vyxeos;
  • (FI) Finland: Vyxeos;
  • (FR) France: Vyxeos;
  • (GB) United Kingdom: Vyxeos;
  • (HU) Hungary: Vyxeos;
  • (IT) Italy: Vyxeos;
  • (NL) Netherlands: Vyxeos;
  • (NO) Norway: Vyxeos;
  • (PL) Poland: Vyxeos;
  • (PR) Puerto Rico: Vyxeos;
  • (SE) Sweden: Vyxeos;
  • (SI) Slovenia: Vyxeos liposomal;
  • (SK) Slovakia: Vyxeos liposomal
  1. <800> Hazardous Drugs–Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. doi: 10.1200/JCO.2016.70.5400. [PubMed 27918725]
  3. Children's Oncology Group (COG). Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. http://www.survivorshipguidelines.org/pdf/2018/COG_LTFU_Guidelines_v5.pdf. Updated October 2018. Accessed May 5, 2021.
  4. Cooper TM, Absalon MJ, Alonzo TA, et al. Phase I/II study of CPX-351 followed by fludarabine, cytarabine, and granulocyte-colony stimulating factor for children with relapsed acute myeloid leukemia: A report from the Children's Oncology Group. J Clin Oncol. 2020;38(19):2170-2177. doi:10.1200/JCO.19.03306 [PubMed 32401633]
  5. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
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  7. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  8. Jazz Pharmaceuticals. Vyxeos dilution in a volume less than 500 mL [written communication]. Palo Alto, CA: Jazz Pharmaceuticals Inc; June 30, 2021.
  9. Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018;36(26):2684-2692. doi:10.1200/JCO.2017.77.6112 [PubMed 30024784]
  10. Paw Cho Sing E, Robinson PD, Flank J, et al. Classification of the acute emetogenicity of chemotherapy in pediatric patients: a clinical practice guideline. Pediatr Blood Cancer. 2019;66(5):e27646. doi:10.1002/pbc.27646 [PubMed 30729654]
  11. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Updated September 2016. Accessed August 7, 2017.
  12. Vyxeos (daunorubicin and cytarabine [liposomal]) [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals Inc; September 2022.
  13. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(36):2768-2801. [PubMed 27567406]
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