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.
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 (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 (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).
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).
(For additional information see "Liposomal daunorubicin and cytarabine: Drug information")
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 (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.
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).
ESRD: 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).
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
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)]
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.
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.
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).
Store intact vials 2°C to 8°C (36°F to 46°F) in an upright position. Protect from light (retain in original container). Reconstituted solution is stable for up to 4 hours when refrigerated. Solutions diluted for infusion (if not used immediately) are stable for up to 4 hours when refrigerated. Reconstituted solution and solution diluted for infusion are stable refrigerated for a total of 4 hours (NOT 4 hours each). If the reconstituted solution was stored refrigerated for 4 hours, the diluted solution for infusion must be used immediately.
Treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) (FDA approved in ages ≥1 year and adults); has also been used for treatment of relapsed pediatric acute myeloid leukemia.
Daunorubicin and cytarabine (liposomal) may be confused with cytarabine (conventional), cytarabine (liposomal), dactinomycin, daunorubicin (conventional), daunorubicin (liposomal), doxorubicin, doxorubicin liposomal, epirubicin, idarubicin, valrubicin
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.
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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Edema (51%), cardiac arrhythmia (30%), cardiotoxicity (20%), hypotension (20%), hypertension (18%), chest pain (17%)
Central nervous system: Headache (33%), fatigue (32%), sleep disorder (25%), chills (23%), dizziness (18%), delirium (16%), anxiety (14%)
Dermatologic: Skin rash (54%), pruritus (15%)
Endocrine & metabolic: Hyponatremia (grades 3/4: 6% to 14%)
Gastrointestinal: Diarrhea (≤66%), nausea (47%), colitis (≤45%), mucositis (44%), constipation (40%), abdominal pain (33%), decreased appetite (29%), vomiting (24%), hemorrhoids (11%)
Hematologic & oncologic: Anemia (100%), neutropenia (100%; grade 4 [prolonged]: 10% to 17%), thrombocytopenia (100%; grade 3 [prolonged]: 25% to 28%), hemorrhage (70%; grades 3 to 5: 10%), febrile neutropenia (68%; grades 3 to 5: 66%), petechia (11%)
Hypersensitivity: Transfusion reaction (11%)
Infection: Bacteremia (24%), fungal infection (18%), sepsis (11%)
Local: Injection site reaction (16%; includes catheter and device site)
Neuromuscular & skeletal: Musculoskeletal pain (38%)
Ophthalmic: Visual impairment (11%)
Renal: Renal insufficiency (11%)
Respiratory: Cough (33%), dyspnea (32%), pneumonia (26%), hypoxia (18%), upper respiratory tract infection (18%), pleural effusion (16%)
Miscellaneous: Fever (17%)
1% to 10%:
Central nervous system: Hallucination (<10%)
Endocrine & metabolic: Hypokalemia (grades 3/4: 6% to 9%), hypoalbuminemia (grades 3/4: 2% to 7%), abnormal alanine aminotransferase (grades 3/4: ≤5%)
Gastrointestinal: Dyspepsia (<10%)
Hepatic: Hyperbilirubinemia (grades 3/4: 2% to 6%)
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%)
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:
• Elderly: 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]).
Refer to individual components.
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
Ado-Trastuzumab Emtansine: May enhance the cardiotoxic effect 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
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
Bevacizumab: May enhance the cardiotoxic effect of Anthracyclines. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cardiac Glycosides: May diminish the cardiotoxic effect of Anthracyclines. Anthracyclines may decrease the serum concentration of Cardiac Glycosides. The effects of liposomal formulations may be unique from those of the free drug, as liposomal formulation have unique drug disposition and toxicity profiles, and liposomes themselves may alter digoxin absorption/distribution. Risk C: Monitor therapy
Cedazuridine: May increase the serum concentration of Cytidine Deaminase Substrates. Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
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: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. 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: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. 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
Cyclophosphamide: May enhance the cardiotoxic effect of Anthracyclines. 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
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fam-Trastuzumab Deruxtecan: May enhance the cardiotoxic effect 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 enhance the myelosuppressive effect of Fexinidazole. 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
Margetuximab: Anthracyclines may enhance the adverse/toxic effect 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
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
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 post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
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
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of 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 Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
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
Taxane Derivatives: May enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Management: Consider separating doxorubicin and paclitaxel administration by as much time as possible, using liposomal doxorubicin or epirubicin instead of doxorubicin, or using docetaxel instead of paclitaxel. Monitor closely for cardiovascular and other toxicities. Risk D: Consider therapy modification
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
Trastuzumab: May enhance the cardiotoxic effect 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 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
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). 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
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.
CBC (prior to treatment and each consolidation cycle), liver and renal function tests (prior to treatment and each consolidation cycle), pregnancy test prior to treatment initiation (in patients who can become pregnant); cardiac function via ECG, multigated acquisition (MUGA), or echocardiogram (ECHO) (prior to treatment initiation, prior to consolidation therapy [via MUGA or ECHO], and as clinically necessary); monitor infusion site (for extravasation), nausea/vomiting, and signs/symptoms of hemorrhage and hypersensitivity reactions.
Patients with Wilson disease or other copper-related metabolic disorders: Total serum copper, serum non-ceruloplasmin bound copper, 24-hour urine copper levels, serial neuropsychological exams.
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).
Suspension (reconstituted) (Vyxeos Intravenous)
44-100 mg (per each): $10,830.00
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