cytarabine/daunorubicin liposomal (Rx)

Brand and Other Names:Vyxeos
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

cytarabine/daunorubicin liposomal

injection, lyophilized cake for reconstitution

  • (100mg/44mg)/vial
  • (5mg/2.2mg)/mL (following reconstitution)

Acute Myeloid Leukemia

Fixed-dose combination for newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC)

Induction

  • First cycle: (Daunorubicin 44 mg/m2 /cytarabine 100 mg/m2) liposome IV on days 1, 3 and 5
  • Second cycle
    • Only for patients failing to achieve a response with first induction cycle
    • May be administered 2-5 weeks after the first cycle if there was no unacceptable toxicity
    • (Daunorubicin 44 mg/m2/cytarabine 100 mg/m2) liposome IV on days 1 and 3 if needed

Consolidation

Consolidation: (Daunorubicin 29 mg/m2/cytarabine 65 mg/m2) liposome IV on days 1 and 3

Initiate first consolidation cycle 5-8 weeks after start of the last induction cycle

Dosage Modifications

Cardiotoxicity

  • Discontinue treatment in patients who exhibit impaired cardiac function unless benefit of continuing treatment outweighs risk

Hypersensitivity reactions

  • For hypersensitivity reactions of any grade/severity, interrupt infusion immediately and manage symptoms
  • Mild symptoms: Once resolved, reinitiate infusion at half the prior infusion rate; consider premedication with antihistamines and/or corticosteroids for subsequent doses
  • Moderate symptoms: Do not reinitiate infusion; for subsequent doses, initiate infusion at same rate and premedicate with antihistamines and/or corticosteroids
  • Severe/life-threatening symptoms: Permanently discontinue; treat symptoms according to standard of care; monitor until symptoms resolve

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
  • Severe (CrCl 15-29 mL/min) or end-stage renal disease: Not studied

Hepatic impairment

  • Bilirubin ≤3 mg/dL: No dosage adjustment necessary
  • Bilirubin >3 mg/dL: Not studied

Dosing Considerations

Monitoring parameters

  • Before initiating treatment
    • Assess cardiac function (electrocardiogram [ECG], multigated radionuclide angiography [MUGA] scan or echocardiography [ECHO])
    • Obtain baseline liver and renal function
    • Verify pregnancy status of females of reproductive potential
  • Each cycle
    • Cardiac function (MUGA, ECHO) before consolidation and as clinically required
    • Liver and renal function

Consolidation

  • Do not start until ANC >0.5 Gi/L and the platelet count >50 Gi/L in the absence of unacceptable toxicity

Dosage Forms & Strengths

cytarabine/daunorubicin liposomal

injection, lyophilized cake for reconstitution

  • (100mg/44mg)/vial
  • (5mg/2.2mg)/mL (following reconstitution)

Acute Myeloid Leukemia

Fixed-dose combination indicated for newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patient aged ≥1 year

Induction

  • First cycle: (Daunorubicin 44 mg/m2 /cytarabine 100 mg/m2) liposome IV on days 1, 3 and 5
  • Second cycle
    • Only for patients failing to achieve a response with first induction cycle
    • May be administered 2-5 weeks after the first cycle if there was no unacceptable toxicity
    • (Daunorubicin 44 mg/m2/cytarabine 100 mg/m2) liposome IV on days 1 and 3 if needed

Consolidation

Consolidation: (Daunorubicin 29 mg/m2/cytarabine 65 mg/m2) liposome IV on days 1 and 3

Initiate first consolidation cycle 5-8 weeks after start of the last induction cycle

Dosage Modifications

Cardiotoxicity

  • Discontinue treatment in patients who exhibit impaired cardiac function unless benefit of continuing treatment outweighs risk

Hypersensitivity reactions

  • For hypersensitivity reactions of any grade/severity, interrupt infusion immediately and manage symptoms
  • Mild symptoms: Once resolved, reinitiate infusion at half the prior infusion rate; consider premedication with antihistamines and/or corticosteroids for subsequent doses
  • Moderate symptoms: Do not reinitiate infusion; for subsequent doses, initiate infusion at same rate and premedicate with antihistamines and/or corticosteroids
  • Severe/life-threatening symptoms: Permanently discontinue; treat symptoms according to standard of care; monitor until symptoms resolve

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
  • Severe (CrCl 15-29 mL/min) or end-stage renal disease: Not studied

Hepatic impairment

  • Bilirubin ≤3 mg/dL: No dosage adjustment necessary
  • Bilirubin >3 mg/dL: Not studied

Dosing Considerations

Monitoring parameters

  • Before initiating treatment
    • Assess cardiac function (ECG, MUGA, or ECHO)
    • Obtain baseline liver and renal function
    • Verify pregnancy status of females of reproductive potential
  • Each cycle

    • Cardiac function (MUGA, ECHO) before consolidation and as clinically required
    • Liver and renal function

Consolidation

Do not start until ANC >0.5 Gi/L and the platelet count >50 Gi/L in the absence of unacceptable toxicity

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Interactions

Interaction Checker

and cytarabine/daunorubicin liposomal

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              Serious - Use Alternative (9)

              • adenovirus types 4 and 7 live, oral

                cytarabine decreases effects of adenovirus types 4 and 7 live, oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3mo after cessation of immunosuppressive therapy.

              • cedazuridine

                cedazuridine will increase the level or effect of cytarabine by decreasing metabolism. Avoid or Use Alternate Drug. Cedazuridine, a CDA inhibitor, is used with decitabine to increase systemic exposure of decitabine. Use with other drugs metabolized by CDA may increase levels and toxicities of those drugs.

              • influenza virus vaccine quadrivalent, adjuvanted

                cytarabine decreases effects of influenza virus vaccine quadrivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.

                daunorubicin liposomal decreases effects of influenza virus vaccine quadrivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.

              • influenza virus vaccine trivalent, adjuvanted

                cytarabine decreases effects of influenza virus vaccine trivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.

              • sotorasib

                sotorasib will decrease the level or effect of daunorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

              • palifermin

                palifermin increases toxicity of cytarabine by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hrbefore, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

              • tepotinib

                tepotinib will increase the level or effect of daunorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

              • tofacitinib

                cytarabine, tofacitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

              • trastuzumab deruxtecan

                trastuzumab deruxtecan, daunorubicin liposomal. Either increases toxicity of the other by unknown mechanism. Avoid or Use Alternate Drug. Trastuzumab may cause cardiomyopathy. Incidence and severity was highest when used with anthracycline-containing chemotherapy regimens. If possible, avoid anthracycline-based therapy for 7 months after last trastuzumab/hyaluronidase dose. If anthracyclines are used, carefully monitor cardiac function.

              Monitor Closely (24)

              • acalabrutinib

                acalabrutinib, cytarabine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects.

              • belatacept

                belatacept and cytarabine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.

              • berotralstat

                berotralstat will increase the level or effect of daunorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

              • cholera vaccine

                cytarabine decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

              • dengue vaccine

                cytarabine decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

              • denosumab

                cytarabine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.

              • dichlorphenamide

                dichlorphenamide and cytarabine both decrease serum potassium. Use Caution/Monitor.

              • digoxin

                cytarabine decreases levels of digoxin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Cytarabine may decrease digoxin absorption even several days after stopping chemotherapy. Digoxin capsules and digitoxin do not appear to be affected. .

              • fingolimod

                cytarabine increases effects of fingolimod by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Concomitant therapy is expected to increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects. .

              • fostemsavir

                fostemsavir will increase the level or effect of daunorubicin liposomal by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits BCRP transporters. If possible, avoid coadministration or modify dose of BCRP substrate coadministered with fostemsavir.

              • hydroxyurea

                cytarabine, hydroxyurea. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of myelosuppression.

              • influenza A (H5N1) vaccine

                cytarabine decreases effects of influenza A (H5N1) vaccine by Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce immune response to H5N1 vaccine.

              • influenza virus vaccine (H5N1), adjuvanted

                cytarabine decreases effects of influenza virus vaccine (H5N1), adjuvanted by Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce immune response to H5N1 vaccine.

              • lonafarnib

                lonafarnib will increase the level or effect of daunorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

              • meningococcal group B vaccine

                cytarabine decreases effects of meningococcal group B vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Individuals with altered immunocompetence may have reduced immune responses to the vaccine.

              • ofatumumab SC

                ofatumumab SC, daunorubicin liposomal. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

                ofatumumab SC, cytarabine. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

              • olaparib

                cytarabine and olaparib both increase pharmacodynamic synergism. Use Caution/Monitor. Coadministration with other other myelosuppressive anticancer agents, including DNA damaging agents, may potentiate and prolongate the myelosuppressive toxicity.

              • trastuzumab deruxtecan

                trastuzumab deruxtecan, daunorubicin liposomal. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • siponimod

                siponimod and cytarabine both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • sipuleucel-T

                cytarabine decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.

              • tobramycin inhaled

                tobramycin inhaled and cytarabine both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

              • trastuzumab

                trastuzumab, cytarabine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • trastuzumab deruxtecan

                trastuzumab deruxtecan, cytarabine. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

              • tucatinib

                tucatinib will increase the level or effect of daunorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

              Minor (5)

              • gentamicin

                cytarabine decreases effects of gentamicin by unspecified interaction mechanism. Minor/Significance Unknown.

              • maitake

                maitake increases effects of cytarabine by pharmacodynamic synergism. Minor/Significance Unknown. Maitake mushroom has anti-tumor effects (animal/in vitro research).

              • taurine

                cytarabine decreases levels of taurine by unspecified interaction mechanism. Minor/Significance Unknown.

              • vitamin A

                vitamin A, cytarabine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • vitamin E

                vitamin E, cytarabine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin E enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

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              Adverse Effects

              >10%

              Hemorrhage, all grades (70%)

              Febrile neutropenia, all grades (68%)

              Febrile neutropenia, ≥grade 3 (66%)

              Rash, all grades (54%)

              Edema, all grades (51%)

              Nausea, all grades (47%)

              Diarrhea/colitis, all grades (45%)

              Abdominal pain, all grades (33%)

              Cough, all grades (33%)

              Headache, all grades (33%)

              Dyspnea, all grades (32%)

              Fatigue, all grades (32%)

              Arrhythmia, all grades (30%)

              Decreased appetite, all grades (29%)

              Prolonged thrombocytopenia, induction (28%)

              Pneumonia (excluding fungal), all grades (26%)

              Sleep disorders, all grades (25%)

              Prolonged thrombocytopenia, consolidation cycle (25%)

              Bacteremia (excluding sepsis), all grades (24%)

              Vomiting, all grades (24%)

              Chills, all grades (23%)

              Bacteremia (excluding sepsis), grade ≥3 (23%)

              Hypotension, all grades (20%)

              Pneumonia (excluding fungal), grade ≥3 (20%)

              Non conduction cardiotoxicity, all grades (20%)

              Mucositis, all grades (44%)

              Musculoskeletal pain, all grades (38%)

              Dizziness, all grades (18%)

              Fungal infection, all grades (18%)

              Hypertension, all grades (18%)

              Hypoxia, all grades (18%)

              Upper respiratory tract infections (excluding fungal), all grades (18%)

              Prolonged neutropenia, induction cycle (17%)

              Chest pain, all grades (17%)

              Pyrexia, all grades (17%)

              Catheter/device/injection site reaction, all grades (16%)

              Delirium, all grades (16%)

              Pleural effusion, all grades (16%)

              Pruritus, all grades (15%)

              Anxiety, all grades (14%)

              Hypoxia, grade ≥3 (13%)

              Hemorrhoids, all grades (11%)

              Petechiae, all grades (11%)

              Renal insufficiency, all grades (11%)

              Transfusion reactions, all grades (11%)

              Visual impairment, all grades (11%)

              Dyspnea (11%)

              1-10%

              Deafness (<10%)

              Deafness unilateral (<10%)

              Eye conjunctivitis (<10%)

              Dry eye (<10%)

              Eye edema (<10%)

              Eye swelling (<10%)

              Eye irritation (<10%)

              Eye pain (<10%)

              Periorbital edema (<10%)

              Scleral hyperemia (<10%)

              Dyspepsia (<10%)

              Hallucinations (<10%)

              Pneumonitis (<10%)

              Prolonged neutropenia, consolidation (10%)

              Hemorrhage, grade ≥3 (10%)

              Hypertension, grade ≥3 (10%)

              Non conduction cardiotoxicity, grade ≥3 (9%)

              Arrhythmia, grade ≥3 (7%)

              Fungal infection, grade ≥3 (7%)

              Rash, grade ≥3 (5%)

              Renal insufficiency, grade ≥3 (5%)

              Upper respiratory tract infections (excluding fungal), grade ≥3 (3%)

              Chest pain, grade ≥3 (3%)

              Delirium, grade ≥3 (3%)

              Edema, grade ≥3 (3%)

              Diarrhea/colitis, grade ≥3 (3%)

              Muscloskeletal pain, grade ≥3 (3%)

              Abdominal pain, grade ≥3 (2%)

              Pleural effusion, grade ≥3 (2%)

              Transfusion reactions, grade ≥3 (2%)

              Headache, grade ≥3 (1%)

              Pyrexia, grade ≥3 (1%)

              Nausea, grade ≥3 (1%)

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              Warnings

              Black Box Warnings

              Do not interchange with other daunorubicin- and/or cytarabine -containing products

              Vyxeos has different dosage recommendations than daunorubicin, cytarabine, liposomal daunorubicin, and liposomal cytarabine

              Do not substitute other preparations of daunorubicin or cytarabine for Vyxeos

              Verify drug name and dose prior to preparation and administration to avoid dosing errors

              Contraindications

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

              Cautions

              Do not interchange with other daunorubicin- and/or cytarabine- containing products

              Serious or fatal hemorrhage events may occur; monitor blood cell counts until recovery and administer platelet transfusion if needed

              Reports of fatal hypersensitivity reactions (eg, anaphylactic reactions); monitor for hypersensitivity reactions

              Severe local tissue necrosis at extravasation site has been associated with daunorubicin; confirm patency of intravenous access before administration; administer IV only; do not administer IM or SC

              May cause embryofetal harm

              Copper overload

              • Reconstituted solution contains 5 mg/mL copper gluconate (14% elemental copper)
              • Maximum theoretical total exposure of copper for dosing regimen is 106 mg/m2
              • No clinical experience in patients with Wilson disease or other copper-related metabolic disorders; use only if benefits outweigh risks
              • Consult with a hepatologist and nephrologist with expertise in managing acute copper toxicity in treated patients with Wilson’s disease
              • Monitor total serum copper, serum nonceruloplasmin bound copper, 24-hr urine copper levels, and serial neuropsychological examinations in these patients
              • Discontinue if signs or symptoms of acute copper toxicity occurs

              Cardiotoxicity

              • Pre-existing cardiac disease, previous radiotherapy to the mediastinum, or concomitant use of cardiotoxic drugs may increase the risk of daunorubicin induced cardiac toxicity
              • Monitor as clinically required; discontinue in patients with impaired cardiac function unless benefit of treatment outweighs the risk
              • Not recommended in patients with abnormal left ventricular ejection fraction
              • Calculate lifetime cumulative anthracycline exposure before each cycle; total cumulative doses of nonliposomal daunorubicin > 550 mg/m2 have been associated with an increased incidence of drug-induced congestive heart failure; tolerable limit appears lower (400 mg/m2) in patients who received radiation therapy to the mediastinum
              • Not recommended in patients whose lifetime anthracycline exposure has reached the maximum cumulative limit
              • Cumulative exposure of daunorubicin
                • First induction cycle: Daunorubicin per dose 44 mg/m2 for 3 doses; daunorubicin per cycle 132 m2
                • Second induction cycle: Daunorubicin per dose 44 mg/m2 for 2 doses; daunorubicin per cycle 88 mg/m2
                • Each consolidation cycle: Daunorubicin per dose 29 mg/m2 for 2 doses; daunorubicin per cycle 58 mg/m2​

              Drug interaction overview

              • Cardiotoxic agents
                • Assess cardiac function more frequently
                • Coadministration with cardiotoxic agents may increase the risk of cardiotoxicity
              • Hepatoxicity
                • Closely monitor hepatic function
                • Coadministration with hepatotoxic agents may impair liver function and increase toxicity
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              Pregnancy & Lactation

              Pregnancy

              Based on data of cytarabine in pregnant females and study results of daunorubicin and cytarabine in animals, embryofetal harm may occur when administered to pregnant females

              There are no adequate and well-controlled studies of Vyxeos, daunorubicin, or cytarabine in pregnant females

              Advise to avoid becoming pregnant during treatment

              If used during pregnancy, or if patient becomes pregnant while taking this drug, apprise patient of the potential harm to a fetus

              Verify pregnancy status of females of reproductive potential before initiating treatment

              Animal data

              • Daunorubicin and cytarabine are reproductive and developmental toxicants in multiple species (mice, rats, and/or dogs), starting dose was ~0.02x the exposure in patients at the recommended human dose on a mg/m2 basis

              Contraception

              • Females and males with female partners of reproductive potential: Use effective contraception during treatment and for at least 6 months after last dose

              Infertility

              • Based on findings of daunorubicin and cytarabine in animals, male fertility may be compromised by treatment

              Lactation

              There are no data on drug presence or its metabolites in human milk, effects on breastfed infants, or effects on milk production

              Advise not to breastfeed during treatment and for at least 2 weeks after the last dose

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Cytarabine and daunorubicin combination encapsulated within a nano scale liposome at a 5:1 molar ratio; selectively ingested by leukemic cells, enhancing efficacy and increasing therapeutic index

              Cytarabine: Metabolite cytarabine-5'-triphosphate inhibits DNA polymerase during S phase

              Daunorubicin: Anthracycline; intercalates between DNA base pairs, impairs topoisomerase II function, inhibits DNA polymerase activity, affects gene expression regulation, and produces DNA-damaging free radicals

              Absorption

              Peak plasma concentration

              • Daunorubicin: 26 mcg/mL
              • Cytarabine: 62.2 mcg/mL

              AUC

              • Daunorubicin: 637 mcg⋅h/mL
              • Cytarabine: 1900 mcg⋅h/mL

              Accumulation ratio

              • Daunorubicin: 1.3
              • Cytarabine: 1.4

              Distribution

              Vd

              • Daunorubicin: 6.6 L
              • Cytarabine: 7.1 L

              Metabolism

              Daunorubicin: Catalyzed by aldoketo reductase and carbonyl reductase enzymes to active metabolite daunorubicinol

              Cytarabine: Metabolized by cytidine deaminase to inactive metabolite 1-β-D-arabinofuranosyluracil (AraU)

              Elimination

              Half-life

              • Daunorubicin: 31.5 hr
              • Cytarabine: 40.4 hr

              Clearance

              • Daunorubicin: 0.16 L/hr
              • Cytarabine: 0.13 L/hr

              Excretion

              • Daunorubicin and daunorubicinol (metabolite): Urine (9%)
              • Cytarabine and AraU (metabolite): Urine (71%)
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              Administration

              IV Incompatibilities

              Do not infuse with other drugs

              IV Compatibilities

              0.9% NaCl, D5W

              IV Preparation

              Reconstitution

              • Remove appropriate number of vials from refrigerator; equilibrate vials to room temperature for 30 minutes
              • Reconstitute each vial with 19 mL of sterile water and immediately swirl vial carefully for 5 minutes; gently inverting vial every 30 seconds, resulting concentration: daunorubicin 2.2 mg/cytarabine 5 mg per mL
              • Do not heat, vortex, or shake vigorously
              • After reconstitution, rest for 15 minutes; reconstituted product should be an opaque, purple, homogeneous dispersion with no visible particulates
              • Gently invert each vial 5 times before further dilution
              • If reconstituted product is not used immediately, refrigerate at 36-46°F (2-8ºC) for up to 4 hr

              Further dilution

              • Use the following formula to calculate volume of reconstituted product required: [volume required (mL) = dose of daunorubicin (mg/m) x patient’s BSA (m ) ÷ 2.2 (mg/mL)]
              • Aseptically withdraw calculated volume of reconstituted product and transfer it to 500 mL of 0.9% NaCl or D5W; discard unused drug
              • If not used immediately, refrigerate at 36-46°F (2-8ºC) for up to 4 hr
              • Visually inspect diluted solutions for particulate matter and discoloration prior to administration

              IV Administration

              For IV use only

              Do not mix with or infuse with other drugs

              Infuse over 90 minutes via a central venous or peripherally inserted central catheter

              Do not use inline filter

              Flush line after administration with 0.9% NaCl or D5W

              Storage

              Cytotoxic drug

              Follow applicable special handling and disposal procedures

              Unopened vials

              • Refrigerate at 36-46ºF (2-8ºC) in an upright position; store in original carton to protect from light
              • Does not contain any preservatives; discard any unused portions

              Reconstituted vials or diluted solutions

              • Refrigerate at 36-46ºF (2-8ºC) for up to 4 hr if not used immediately
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              Images

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.